Ignite Creation Date:
2025-12-24 @ 9:34 PM
Ignite Modification Date:
2026-02-22 @ 9:38 AM
Study NCT ID:
NCT01703832
Status:
COMPLETED
Last Update Posted:
2015-02-11
First Post:
2012-10-08
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Explorative Open Label Study of Efficacy Profile of Neurexan® in Experimental Acute Stress Setting in Healthy Subjects
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D040701', 'term': 'Stress Disorders, Traumatic, Acute'}], 'ancestors': [{'id': 'D040921', 'term': 'Stress Disorders, Traumatic'}, {'id': 'D000068099', 'term': 'Trauma and Stressor Related Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C483503', 'term': 'neurexan'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'christine.frank@heel.com', 'phone': '+49 7221 501 3188', 'title': 'Christine Frank, PhD', 'organization': 'Biologische Heilmittel Heel GmbH'}, 'certainAgreement': {'otherDetails': 'Investigator agreements in place restricting the PI from independently publishing the study results. Currently working with both PIs on several publications of the NEUPRO studies.', 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'Randomization until individual study end', 'description': 'All adverse events that occurred after the participant has received at least one dose of the product under investigation were to be collected and reported', 'eventGroups': [{'id': 'EG000', 'title': 'Neurexan®', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.', 'otherNumAtRisk': 33, 'otherNumAffected': 4, 'seriousNumAtRisk': 33, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'No Intervention', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.', 'otherNumAtRisk': 32, 'otherNumAffected': 3, 'seriousNumAtRisk': 32, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Procedural Pain', 'notes': 'Pain during insertion of catheter', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 32, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Procedural dizziness', 'notes': 'Dizziness as result from blood catheter insertion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 32, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Procedural nausea', 'notes': 'Nausea during insertion of catheter', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 32, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Aspartate aminotransferase increased', 'notes': 'Increased transaminases (GOT)', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 32, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Alanine aminotransferase increased', 'notes': 'increase in transaminases (GPT)', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 32, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Dizziness', 'notes': 'Dizziness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 32, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Headache', 'notes': 'Mild Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 32, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}, {'term': 'Dry Mouth', 'notes': 'Dry Mouth', 'stats': [{'groupId': 'EG000', 'numAtRisk': 33, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 32, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (15.1)'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Acute Stress Measured by Tension', 'denoms': [{'units': 'Participants', 'counts': [{'value': '32', 'groupId': 'OG000'}, {'value': '32', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Neurexan®', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.'}, {'id': 'OG001', 'title': 'No Intervention', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.'}], 'classes': [{'categories': [{'measurements': [{'value': '3089.4', 'groupId': 'OG000', 'lowerLimit': '40', 'upperLimit': '20940'}, {'value': '3253.4', 'groupId': 'OG001', 'lowerLimit': '308', 'upperLimit': '19305'}]}]}], 'analyses': [{'pValue': '0.1233', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Threshold less than or equal to 0.05. The final analysis demonstrated reasonable doubt of the implicit normality assumption of the two sets of AUC data, thus medians presented for efficacy analysis. Need for further investigation (ex-post analyses).', 'groupDescription': 'The null-hypotheses of no treatment differences were tested by the two-sided t-tests from the respective ANCOVAs.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEDIAN', 'timeFrame': '-210 minutes to +100 minutes', 'description': 'Tension and nervousness were self-assessed by the participants on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) before and after a stress test. The VAS is used to determine the subjective impression of tension and nervousness on a 10 cm bipolar visual scale ranging from 0 = "not at all" to 100 = "highly". The measurements started with first intake of Neurexan or Natural Course and were repeated until 100 minutes after the end of the stress test. The total stress was then summarized with the Area under the curve (AUC) method.', 'unitOfMeasure': 'mm*min', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': '33 participants were randomized to Neurexan and 32 participants to Natural Course and all randomized participants were included in the Safety Set. 32 Neurexan and 32 Natural Course participants that could be evaluated for primary efficacy formed the Full Analysis Set for analysis of efficacy.'}, {'type': 'PRIMARY', 'title': 'Acute Stress Measured by Nervousness', 'denoms': [{'units': 'Participants', 'counts': [{'value': '32', 'groupId': 'OG000'}, {'value': '32', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Neurexan®', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.'}, {'id': 'OG001', 'title': 'No Intervention', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.'}], 'classes': [{'categories': [{'measurements': [{'value': '2377.3', 'groupId': 'OG000', 'lowerLimit': '12', 'upperLimit': '9071'}, {'value': '3426.8', 'groupId': 'OG001', 'lowerLimit': '329', 'upperLimit': '14898'}]}]}], 'analyses': [{'pValue': '0.5153', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Threshold less than or equal to 0.05. The final analysis demonstrated reasonable doubt of the implicit normality assumption of the two sets of AUC data, thus medians presented for efficacy analysis. Need for further investigation (ex-post analyses).', 'groupDescription': 'The null-hypotheses of no treatment differences were tested by the two-sided t-tests from the respective ANCOVAs.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEDIAN', 'timeFrame': '-210 minutes to +100 minutes', 'description': 'Tension and nervousness were self-assessed by the participants on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) before and after a stress test. The VAS is used to determine the subjective impression of tension and nervousness on a 10 cm bipolar visual scale ranging from 0 = "not at all" to 100 = "highly". The measurements started with first intake of Neurexan or Natural Course and were repeated until 100 minutes after the end of the stress test. The total stress was then summarized with the Area under the curve (AUC) method.', 'unitOfMeasure': 'mm*min', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': '33 participants were randomized to Neurexan and 32 participants to Natural Course and all randomized participants were included in the Safety Set. 32 Neurexan and 32 Natural Course participants that could be evaluated for primary efficacy formed the Full Analysis Set for analysis of efficacy.'}, {'type': 'SECONDARY', 'title': 'Changes in Saliva Alpha Amylase', 'denoms': [{'units': 'Participants', 'counts': [{'value': '32', 'groupId': 'OG000'}, {'value': '32', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Neurexan®', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.'}, {'id': 'OG001', 'title': 'No Intervention', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.'}], 'classes': [{'title': '-60 min', 'categories': [{'measurements': [{'value': '155.6', 'groupId': 'OG000', 'lowerLimit': '21.6', 'upperLimit': '594.9'}, {'value': '133.2', 'groupId': 'OG001', 'lowerLimit': '11.5', 'upperLimit': '591.8'}]}]}, {'title': '+15 min', 'categories': [{'measurements': [{'value': '242.8', 'groupId': 'OG000', 'lowerLimit': '28.2', 'upperLimit': '620.3'}, {'value': '204.9', 'groupId': 'OG001', 'lowerLimit': '9.8', 'upperLimit': '819.9'}]}]}, {'title': '+45 min', 'categories': [{'measurements': [{'value': '171.3', 'groupId': 'OG000', 'lowerLimit': '21.0', 'upperLimit': '786.5'}, {'value': '138.6', 'groupId': 'OG001', 'lowerLimit': '9.6', 'upperLimit': '812.8'}]}]}, {'title': '+100 min', 'categories': [{'measurements': [{'value': '195.8', 'groupId': 'OG000', 'lowerLimit': '17.4', 'upperLimit': '597.4'}, {'value': '144.0', 'groupId': 'OG001', 'lowerLimit': '8.0', 'upperLimit': '509.3'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '-60 minute, +15 minute , + 45 minute, +100 minute', 'description': 'The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.', 'unitOfMeasure': 'IU/mL', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': '33 participants were randomized to Neurexan and 32 participants to Natural Course and all randomized participants were included in the Safety Set. 32 Neurexan and 32 Natural Course participants that could be evaluated for primary efficacy formed the Full Analysis Set for efficacy. Note: -60 minute time-point had 31 evaluable Neurexan participants.'}, {'type': 'SECONDARY', 'title': 'Changes in Saliva Cortisol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '32', 'groupId': 'OG000'}, {'value': '32', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Neurexan®', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.'}, {'id': 'OG001', 'title': 'No Intervention', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.'}], 'classes': [{'title': '-60 min', 'categories': [{'measurements': [{'value': '7.9', 'groupId': 'OG000', 'lowerLimit': '1.6', 'upperLimit': '27.6'}, {'value': '8.1', 'groupId': 'OG001', 'lowerLimit': '2.8', 'upperLimit': '8.1'}]}]}, {'title': '+15 min', 'categories': [{'measurements': [{'value': '20.3', 'groupId': 'OG000', 'lowerLimit': '2.5', 'upperLimit': '121.1'}, {'value': '19.8', 'groupId': 'OG001', 'lowerLimit': '3.4', 'upperLimit': '112.9'}]}]}, {'title': '+45 min', 'categories': [{'measurements': [{'value': '18.8', 'groupId': 'OG000', 'lowerLimit': '1.2', 'upperLimit': '65.4'}, {'value': '20.6', 'groupId': 'OG001', 'lowerLimit': '3.4', 'upperLimit': '89.6'}]}]}, {'title': '+100 min', 'categories': [{'measurements': [{'value': '8.6', 'groupId': 'OG000', 'lowerLimit': '1.8', 'upperLimit': '24.9'}, {'value': '9.4', 'groupId': 'OG001', 'lowerLimit': '2.6', 'upperLimit': '33.6'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '-60 minutes, +15 minutes, +45 minutes, +100 minutes', 'description': 'The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.', 'unitOfMeasure': 'nmol/mL', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': '33 participants were randomized to Neurexan and 32 participants to Natural Course and all randomized participants were included in the Safety Set. 32 Neurexan and 32 Natural Course participants that could be evaluated for primary efficacy formed the Full Analysis Set for analysis of efficacy.'}, {'type': 'SECONDARY', 'title': 'Changes in Plasma Adrenocorticotropic Hormone (ACTH)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '31', 'groupId': 'OG000'}, {'value': '24', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Neurexan®', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.'}, {'id': 'OG001', 'title': 'No Intervention', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.'}], 'classes': [{'title': '-60 min', 'categories': [{'measurements': [{'value': '20.8', 'groupId': 'OG000', 'lowerLimit': '6.1', 'upperLimit': '283.8'}, {'value': '20.0', 'groupId': 'OG001', 'lowerLimit': '8.0', 'upperLimit': '113.0'}]}]}, {'title': '+15 min', 'categories': [{'measurements': [{'value': '35.4', 'groupId': 'OG000', 'lowerLimit': '13.4', 'upperLimit': '116.9'}, {'value': '31.0', 'groupId': 'OG001', 'lowerLimit': '11.4', 'upperLimit': '158.1'}]}]}, {'title': '+45 min', 'categories': [{'measurements': [{'value': '20.4', 'groupId': 'OG000', 'lowerLimit': '9.1', 'upperLimit': '55.7'}, {'value': '20.6', 'groupId': 'OG001', 'lowerLimit': '7.5', 'upperLimit': '84.1'}]}]}, {'title': '+100 min', 'categories': [{'measurements': [{'value': '11.8', 'groupId': 'OG000', 'lowerLimit': '7.0', 'upperLimit': '33.0'}, {'value': '13.7', 'groupId': 'OG001', 'lowerLimit': '3.3', 'upperLimit': '32.6'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '-60 minutes, +15 minutes, +45 minutes, +100 minutes', 'description': 'The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.', 'unitOfMeasure': 'ng/L', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': '33 participants were randomized to Neurexan and 32 to Natural Course and all randomized participants were included in the Safety Set. For plasma ACTH evaluation 31 Neurexan and 24 Natural Course participants were evaluated due to insufficient samples and the -60 min time-point had 30 evaluable Neurexan participants.'}, {'type': 'SECONDARY', 'title': 'Changes in Plasma Cortisol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '31', 'groupId': 'OG000'}, {'value': '24', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Neurexan®', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.'}, {'id': 'OG001', 'title': 'No Intervention', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.'}], 'classes': [{'title': '-60 min', 'categories': [{'measurements': [{'value': '365.9', 'groupId': 'OG000', 'lowerLimit': '105.1', 'upperLimit': '918.0'}, {'value': '337.6', 'groupId': 'OG001', 'lowerLimit': '125.5', 'upperLimit': '836.5'}]}]}, {'title': '+15 min', 'categories': [{'measurements': [{'value': '554.3', 'groupId': 'OG000', 'lowerLimit': '72.2', 'upperLimit': '971.2'}, {'value': '544.3', 'groupId': 'OG001', 'lowerLimit': '124.5', 'upperLimit': '942.5'}]}]}, {'title': '+45 min', 'categories': [{'measurements': [{'value': '466.8', 'groupId': 'OG000', 'lowerLimit': '73.7', 'upperLimit': '842.2'}, {'value': '506.8', 'groupId': 'OG001', 'lowerLimit': '121.6', 'upperLimit': '815.2'}]}]}, {'title': '+100 min', 'categories': [{'measurements': [{'value': '285.1', 'groupId': 'OG000', 'lowerLimit': '84.0', 'upperLimit': '735.4'}, {'value': '251.4', 'groupId': 'OG001', 'lowerLimit': '136.7', 'upperLimit': '637.7'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '-60 minutes, +15 minutes, +45 minutes, +100 minutes', 'description': 'The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.', 'unitOfMeasure': 'nmol/L', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': '33 participants were randomized to Neurexan and 32 participants to Natural Course and all randomized participants were included in the Safety Set. For the plasma Cortisol evaluation 31 Neurexan and 24 Natural Course participants were evaluated due to insufficient sample.'}, {'type': 'SECONDARY', 'title': 'Changes in Plasma Catecholamines (Epinephrine)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '30', 'groupId': 'OG000'}, {'value': '23', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Neurexan®', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.'}, {'id': 'OG001', 'title': 'No Intervention', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.'}], 'classes': [{'title': '-60 min', 'categories': [{'measurements': [{'value': '44.6', 'groupId': 'OG000', 'lowerLimit': '10.0', 'upperLimit': '108.0'}, {'value': '37.0', 'groupId': 'OG001', 'lowerLimit': '11.0', 'upperLimit': '98.6'}]}]}, {'title': '+15 min', 'categories': [{'measurements': [{'value': '58.2', 'groupId': 'OG000', 'lowerLimit': '10.0', 'upperLimit': '146.0'}, {'value': '40.2', 'groupId': 'OG001', 'lowerLimit': '10.0', 'upperLimit': '88.4'}]}]}, {'title': '+45 min', 'categories': [{'measurements': [{'value': '37.3', 'groupId': 'OG000', 'lowerLimit': '10.0', 'upperLimit': '105.0'}, {'value': '32.0', 'groupId': 'OG001', 'lowerLimit': '9.1', 'upperLimit': '95.5'}]}]}, {'title': '+100 min', 'categories': [{'measurements': [{'value': '29.8', 'groupId': 'OG000', 'lowerLimit': '0.0', 'upperLimit': '87.7'}, {'value': '33.0', 'groupId': 'OG001', 'lowerLimit': '10.0', 'upperLimit': '104.0'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '-60 minutes, +15 minutes, +45 minutes, +100 minutes', 'description': 'The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.', 'unitOfMeasure': 'ng/L', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': '33 participants were randomized to Neurexan and 32 participants to Natural Course and all randomized participants were included in the Safety Set. For plasma Epinephrine evaluation 30 Neurexan and 23 Natural Course participants were evaluated due to insufficient sample.'}, {'type': 'SECONDARY', 'title': 'Changes in Plasma Catecholamines (Norepinephrine)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '30', 'groupId': 'OG000'}, {'value': '23', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Neurexan®', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.'}, {'id': 'OG001', 'title': 'No Intervention', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.'}], 'classes': [{'title': '-60 min', 'categories': [{'measurements': [{'value': '484.5', 'groupId': 'OG000', 'lowerLimit': '249', 'upperLimit': '923'}, {'value': '457.0', 'groupId': 'OG001', 'lowerLimit': '195', 'upperLimit': '797'}]}]}, {'title': '+15 min', 'categories': [{'measurements': [{'value': '575.5', 'groupId': 'OG000', 'lowerLimit': '299', 'upperLimit': '1128'}, {'value': '529.0', 'groupId': 'OG001', 'lowerLimit': '279', 'upperLimit': '1688'}]}]}, {'title': '+45 min', 'categories': [{'measurements': [{'value': '458.0', 'groupId': 'OG000', 'lowerLimit': '220', 'upperLimit': '889'}, {'value': '459.0', 'groupId': 'OG001', 'lowerLimit': '223', 'upperLimit': '858'}]}]}, {'title': '+100 min', 'categories': [{'measurements': [{'value': '467.0', 'groupId': 'OG000', 'lowerLimit': '269', 'upperLimit': '938'}, {'value': '372.0', 'groupId': 'OG001', 'lowerLimit': '189', 'upperLimit': '839'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '-60 minutes, +15 minutes, +45 minutes, +100 minutes', 'description': 'The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.', 'unitOfMeasure': 'ng/L', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': '33 participants were randomized to Neurexan and 32 participants to Natural Course and all randomized participants were included in the Safety Set. For plasma Norepinephrine evaluation 30 Neurexan and 23 Natural Course participants were evaluated due to insufficient sample.'}, {'type': 'SECONDARY', 'title': 'Changes in Natural Killer (NK) Cells (Subgroup)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '12', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Neurexan®', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.'}, {'id': 'OG001', 'title': 'No Intervention', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.'}], 'classes': [{'title': '-60 min', 'categories': [{'measurements': [{'value': '11.8', 'groupId': 'OG000', 'lowerLimit': '5.8', 'upperLimit': '22.6'}, {'value': '11.2', 'groupId': 'OG001', 'lowerLimit': '5.6', 'upperLimit': '16.5'}]}]}, {'title': '+15 min', 'categories': [{'measurements': [{'value': '21.3', 'groupId': 'OG000', 'lowerLimit': '9.8', 'upperLimit': '28.1'}, {'value': '17.7', 'groupId': 'OG001', 'lowerLimit': '10.1', 'upperLimit': '26.2'}]}]}, {'title': '+45 min', 'categories': [{'measurements': [{'value': '11.6', 'groupId': 'OG000', 'lowerLimit': '4.6', 'upperLimit': '14.8'}, {'value': '8.6', 'groupId': 'OG001', 'lowerLimit': '4.3', 'upperLimit': '12.7'}]}]}, {'title': '+100 min', 'categories': [{'measurements': [{'value': '11.1', 'groupId': 'OG000', 'lowerLimit': '6.1', 'upperLimit': '18.2'}, {'value': '7.8', 'groupId': 'OG001', 'lowerLimit': '4.0', 'upperLimit': '20.3'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '-60 minutes, +15 minutes, +45 minutes, +100 minutes', 'description': 'The Natural Killer Cells as immune cells and stress biomarkers were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.', 'unitOfMeasure': 'percentage of lymphocytes', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'The test was only conducted in the Essen site where 15 participants randomized to Neurexan and 12 participants randomized to Natural Course could be evaluated for NK cells'}, {'type': 'SECONDARY', 'title': 'Changes in Blood Pressure', 'denoms': [{'units': 'Participants', 'counts': [{'value': '32', 'groupId': 'OG000'}, {'value': '32', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Neurexan®', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.'}, {'id': 'OG001', 'title': 'No Intervention', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.'}], 'classes': [{'title': 'Systolic blood pressure -15 min', 'categories': [{'measurements': [{'value': '120.5', 'groupId': 'OG000', 'lowerLimit': '86', 'upperLimit': '175'}, {'value': '123.5', 'groupId': 'OG001', 'lowerLimit': '95', 'upperLimit': '147'}]}]}, {'title': 'Systolic blood pressure 0 min', 'categories': [{'measurements': [{'value': '131.0', 'groupId': 'OG000', 'lowerLimit': '98', 'upperLimit': '204'}, {'value': '136.5', 'groupId': 'OG001', 'lowerLimit': '96', 'upperLimit': '171'}]}]}, {'title': 'Systolic blood pressure +15 min', 'categories': [{'measurements': [{'value': '123.0', 'groupId': 'OG000', 'lowerLimit': '92', 'upperLimit': '161'}, {'value': '128.5', 'groupId': 'OG001', 'lowerLimit': '86', 'upperLimit': '165'}]}]}, {'title': 'Systolic blood pressure +45 min', 'categories': [{'measurements': [{'value': '121.0', 'groupId': 'OG000', 'lowerLimit': '77', 'upperLimit': '180'}, {'value': '122.0', 'groupId': 'OG001', 'lowerLimit': '91', 'upperLimit': '160'}]}]}, {'title': 'Diastolic blood pressure -15 min', 'categories': [{'measurements': [{'value': '78.0', 'groupId': 'OG000', 'lowerLimit': '51', 'upperLimit': '120'}, {'value': '79.0', 'groupId': 'OG001', 'lowerLimit': '56', 'upperLimit': '103'}]}]}, {'title': 'Diastolic blood pressure 0 min', 'categories': [{'measurements': [{'value': '83.5', 'groupId': 'OG000', 'lowerLimit': '59', 'upperLimit': '138'}, {'value': '88.5', 'groupId': 'OG001', 'lowerLimit': '60', 'upperLimit': '114'}]}]}, {'title': 'Diastolic blood pressure +15 min', 'categories': [{'measurements': [{'value': '81.5', 'groupId': 'OG000', 'lowerLimit': '54', 'upperLimit': '115'}, {'value': '83.0', 'groupId': 'OG001', 'lowerLimit': '54', 'upperLimit': '109'}]}]}, {'title': 'Diastolic blood pressure +45 min', 'categories': [{'measurements': [{'value': '78.5', 'groupId': 'OG000', 'lowerLimit': '40', 'upperLimit': '124'}, {'value': '81.0', 'groupId': 'OG001', 'lowerLimit': '41', 'upperLimit': '109'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '-15 minutes, 0 minutes, +15 minutes, +45 minutes', 'description': 'Blood pressure and heart rate were measured before and after a stress test by continuous cardiovascular recording.\n\nThe measurements started 30 minutes before stress test and were repeated until 45 minutes after the end of the stress test.', 'unitOfMeasure': 'mmHg', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': '33 participants were randomized to Neurexan and 32 participants to Natural Course and all randomized participants were included in the Safety Set. 32 Neurexan and 32 Natural Course participants that could be evaluated for primary efficacy formed the Full Analysis Set for analysis of efficacy.'}, {'type': 'SECONDARY', 'title': 'Changes in Heart Rate', 'denoms': [{'units': 'Participants', 'counts': [{'value': '32', 'groupId': 'OG000'}, {'value': '32', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Neurexan®', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.'}, {'id': 'OG001', 'title': 'No Intervention', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.'}], 'classes': [{'title': '-15 min', 'categories': [{'measurements': [{'value': '67.0', 'groupId': 'OG000', 'lowerLimit': '55', 'upperLimit': '96'}, {'value': '69.0', 'groupId': 'OG001', 'lowerLimit': '49', 'upperLimit': '98'}]}]}, {'title': '0 min', 'categories': [{'measurements': [{'value': '87.0', 'groupId': 'OG000', 'lowerLimit': '67', 'upperLimit': '135'}, {'value': '83.0', 'groupId': 'OG001', 'lowerLimit': '56', 'upperLimit': '125'}]}]}, {'title': '+15 min', 'categories': [{'measurements': [{'value': '68.0', 'groupId': 'OG000', 'lowerLimit': '54', 'upperLimit': '90'}, {'value': '71.0', 'groupId': 'OG001', 'lowerLimit': '44', 'upperLimit': '93'}]}]}, {'title': '+45 min', 'categories': [{'measurements': [{'value': '68.0', 'groupId': 'OG000', 'lowerLimit': '56', 'upperLimit': '96'}, {'value': '72.0', 'groupId': 'OG001', 'lowerLimit': '48', 'upperLimit': '92'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '-15 minutes, 0 minutes, +15 minutes, +45 minutes', 'description': 'Blood pressure and heart rate were measured before and after a stress test by continuous cardiovascular recording.\n\nThe measurements started 30 minutes before stress test and were repeated until 45 minutes after the end of the stress test.', 'unitOfMeasure': 'beats per minute', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': '33 participants were randomized to Neurexan and 32 participants to Natural Course and all randomized participants were included in the Safety Set. 32 Neurexan and 32 Natural Course participants that could be evaluated for primary efficacy formed the Full Analysis Set for analysis of efficacy.'}, {'type': 'SECONDARY', 'title': 'State Anxiety and Stress Perception Measured by STAI-X1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '32', 'groupId': 'OG000'}, {'value': '32', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Neurexan®', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.'}, {'id': 'OG001', 'title': 'No Intervention', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.'}], 'classes': [{'title': '-90 min', 'categories': [{'measurements': [{'value': '32.0', 'groupId': 'OG000', 'lowerLimit': '21', 'upperLimit': '49'}, {'value': '33.0', 'groupId': 'OG001', 'lowerLimit': '22', 'upperLimit': '43'}]}]}, {'title': '+ 15 min', 'categories': [{'measurements': [{'value': '51.0', 'groupId': 'OG000', 'lowerLimit': '33', 'upperLimit': '73'}, {'value': '56.0', 'groupId': 'OG001', 'lowerLimit': '29', 'upperLimit': '78'}]}]}, {'title': '+100 min', 'categories': [{'measurements': [{'value': '32.0', 'groupId': 'OG000', 'lowerLimit': '21', 'upperLimit': '43'}, {'value': '32.0', 'groupId': 'OG001', 'lowerLimit': '20', 'upperLimit': '52'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '-90 minutes, +15 minutes, +100 minutes', 'description': 'State anxiety and stress perception were measured by State-Trait Anxiety Inventory X1 before and after a stress test. The measurements took place 90 minutes before stress test and were repeated 15 and 100 minutes after the end of the stress test. The German version of the State-Trait-Anxiety Inventory was used and differentiates between temporary/emotional state anxiety versus personality trait anxiety. The two scales with 20 items each assess (1) anxiety as a trait (STAI-X2) and (2) anxiety as a state (STAI-XI). Answers are given in a 4-point rating scale ranging from 1 ="not at all" to 4 ="very true". For analysis of each, STAI-scale single scores were summed up to one total score, representing the state and trait anxiety. Score range is 20-80 and higher scores indicate a higher anxiety.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': '33 participants were randomized to Neurexan and 32 participants to Natural Course and all randomized participants were included in the Safety Set. 32 Neurexan and 32 Natural Course participants that could be evaluated for primary efficacy formed the Full Analysis Set for analysis of efficacy.'}, {'type': 'SECONDARY', 'title': 'Psychological Questionnaire (Modified Somatic SCL90)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '32', 'groupId': 'OG000'}, {'value': '32', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Neurexan®', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.'}, {'id': 'OG001', 'title': 'No Intervention', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.'}], 'classes': [{'title': '-210 min', 'categories': [{'measurements': [{'value': '0.042', 'groupId': 'OG000', 'lowerLimit': '0.00', 'upperLimit': '0.67'}, {'value': '0.083', 'groupId': 'OG001', 'lowerLimit': '0.00', 'upperLimit': '1.08'}]}]}, {'title': '+ 100 min', 'categories': [{'measurements': [{'value': '0.000', 'groupId': 'OG000', 'lowerLimit': '0.00', 'upperLimit': '0.50'}, {'value': '0.000', 'groupId': 'OG001', 'lowerLimit': '0.00', 'upperLimit': '0.33'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '-210 minutes, +100 minutes', 'description': 'The SCL90 has 90 items with dimensions like depression, somatization, obsessive-compulsive disorder, social insecurity, anxiety, phobic anxiety, aggression/hostility, paranoid ideation, psychoticism and each item in a subscale ranged from 0 to 4. The lower range values are favorable outcomes and higher are worse outcomes. The modified somatic SCL90 uses the SCL90 somatization items, but instead of a 7 day timeframe asks for "now". The corresponding items from SCL90 were: 1, 4, 12, 27, 40, 42, 48, 49, 52, 53, 56, 58 and the introductory question: "How much do you currently suffer from" ("Wie sehr leiden Sie momentan unter:"). The median of the average Modified Somatic SCL90 score is reported. The average score was calculated at each time point as the sum score divided by the number of non-missing individual question results for subjects with no more than 2 missing responses. The lower values in the range represent favorable outcomes while the higher values represent worse outcomes.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': '33 participants were randomized to Neurexan and 32 participants to Natural Course and all randomized participants were included in the Safety Set. 32 Neurexan and 32 Natural Course participants that could be evaluated for primary efficacy formed the Full Analysis Set for analysis of efficacy.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Neurexan®', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.'}, {'id': 'FG001', 'title': 'No Intervention', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '33'}, {'groupId': 'FG001', 'numSubjects': '32'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '32'}, {'groupId': 'FG001', 'numSubjects': '32'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Recruitment was carried out in 2 outpatient clinics in Germany (Marburg and Essen).', 'preAssignmentDetails': 'All 65 healthy participants were enrolled and none were excluded prior to randomization.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '33', 'groupId': 'BG000'}, {'value': '32', 'groupId': 'BG001'}, {'value': '65', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Neurexan®', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) took a total of 6 tablets of Neurexan over a period of 2.5 hours.'}, {'id': 'BG001', 'title': 'No Intervention', 'description': 'At baseline, healthy male or female participants with an age of between 31 to 59 years and the ability to understand the explanations and instructions given by the study physician (fluency in German) underwent natural course, i.e. no tablet intake or other therapeutic intervention.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '42.6', 'spread': '8.4', 'groupId': 'BG000'}, {'value': '41.3', 'spread': '8.3', 'groupId': 'BG001'}, {'value': '41.9', 'spread': '8.3', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': '33 participants were randomized to Neurexan and 32 participants to Natural Course. All randomized participants were included in the Safety Set. One premature terminator could not be evaluated for primary efficacy, so 32 participants in the Neurexan group and 32 participants in the Natural Course group formed the Full Analysis Set for analysis of efficacy.', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '33', 'groupId': 'BG000'}, {'value': '32', 'groupId': 'BG001'}, {'value': '65', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'description': '33 participants were randomized to Neurexan and 32 participants to Natural Course. All randomized participants were included in the Safety Set. One premature terminator could not be evaluated for primary efficacy, so 32 participants in the Neurexan group and 32 participants in the Natural Course group formed the Full Analysis Set for analysis of efficacy.', 'unitOfMeasure': 'Participants'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '16', 'groupId': 'BG000'}, {'value': '15', 'groupId': 'BG001'}, {'value': '31', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '17', 'groupId': 'BG000'}, {'value': '17', 'groupId': 'BG001'}, {'value': '34', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'description': '33 participants were randomized to Neurexan and 32 participants to Natural Course. All randomized participants were included in the Safety Set. One premature terminator could not be evaluated for primary efficacy, so 32 participants in the Neurexan group and 32 participants in the Natural Course group formed the Full Analysis Set for analysis of efficacy.', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'Germany', 'categories': [{'measurements': [{'value': '33', 'groupId': 'BG000'}, {'value': '32', 'groupId': 'BG001'}, {'value': '65', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'description': '33 participants were randomized to Neurexan and 32 participants to Natural Course. All randomized participants were included in the Safety Set. One premature terminator could not be evaluated for primary efficacy, so 32 participants in the Neurexan group and 32 participants in the Natural Course group formed the Full Analysis Set for analysis of efficacy.', 'unitOfMeasure': 'participants'}], 'populationDescription': '33 participants were randomized to Neurexan and 32 participants to Natural Course. All randomized participants were included in the Safety Set. One premature terminator could not be evaluated for primary efficacy, so 32 participants in the Neurexan group and 32 participants in the Natural Course group formed the Full Analysis Set for efficacy.'}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 65}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2012-10'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2015-02', 'completionDateStruct': {'date': '2013-04', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2015-02-09', 'studyFirstSubmitDate': '2012-10-08', 'resultsFirstSubmitDate': '2014-08-01', 'studyFirstSubmitQcDate': '2012-10-10', 'lastUpdatePostDateStruct': {'date': '2015-02-11', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2015-02-09', 'studyFirstPostDateStruct': {'date': '2012-10-11', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2015-02-11', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2013-04', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Acute Stress Measured by Tension', 'timeFrame': '-210 minutes to +100 minutes', 'description': 'Tension and nervousness were self-assessed by the participants on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) before and after a stress test. The VAS is used to determine the subjective impression of tension and nervousness on a 10 cm bipolar visual scale ranging from 0 = "not at all" to 100 = "highly". The measurements started with first intake of Neurexan or Natural Course and were repeated until 100 minutes after the end of the stress test. The total stress was then summarized with the Area under the curve (AUC) method.'}, {'measure': 'Acute Stress Measured by Nervousness', 'timeFrame': '-210 minutes to +100 minutes', 'description': 'Tension and nervousness were self-assessed by the participants on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) before and after a stress test. The VAS is used to determine the subjective impression of tension and nervousness on a 10 cm bipolar visual scale ranging from 0 = "not at all" to 100 = "highly". The measurements started with first intake of Neurexan or Natural Course and were repeated until 100 minutes after the end of the stress test. The total stress was then summarized with the Area under the curve (AUC) method.'}], 'secondaryOutcomes': [{'measure': 'Changes in Saliva Alpha Amylase', 'timeFrame': '-60 minute, +15 minute , + 45 minute, +100 minute', 'description': 'The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.'}, {'measure': 'Changes in Saliva Cortisol', 'timeFrame': '-60 minutes, +15 minutes, +45 minutes, +100 minutes', 'description': 'The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.'}, {'measure': 'Changes in Plasma Adrenocorticotropic Hormone (ACTH)', 'timeFrame': '-60 minutes, +15 minutes, +45 minutes, +100 minutes', 'description': 'The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.'}, {'measure': 'Changes in Plasma Cortisol', 'timeFrame': '-60 minutes, +15 minutes, +45 minutes, +100 minutes', 'description': 'The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.'}, {'measure': 'Changes in Plasma Catecholamines (Epinephrine)', 'timeFrame': '-60 minutes, +15 minutes, +45 minutes, +100 minutes', 'description': 'The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.'}, {'measure': 'Changes in Plasma Catecholamines (Norepinephrine)', 'timeFrame': '-60 minutes, +15 minutes, +45 minutes, +100 minutes', 'description': 'The stress biomarkers plasma and saliva cortisol and alpha amylase and Adrenocorticotropic Hormone and catecholamines (norepinephrine and epinephrine) were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.'}, {'measure': 'Changes in Natural Killer (NK) Cells (Subgroup)', 'timeFrame': '-60 minutes, +15 minutes, +45 minutes, +100 minutes', 'description': 'The Natural Killer Cells as immune cells and stress biomarkers were measured before and after a stress test. The measurements started 60 minutes before stress test and were repeated until 100 minutes after the end of the stress test.'}, {'measure': 'Changes in Blood Pressure', 'timeFrame': '-15 minutes, 0 minutes, +15 minutes, +45 minutes', 'description': 'Blood pressure and heart rate were measured before and after a stress test by continuous cardiovascular recording.\n\nThe measurements started 30 minutes before stress test and were repeated until 45 minutes after the end of the stress test.'}, {'measure': 'Changes in Heart Rate', 'timeFrame': '-15 minutes, 0 minutes, +15 minutes, +45 minutes', 'description': 'Blood pressure and heart rate were measured before and after a stress test by continuous cardiovascular recording.\n\nThe measurements started 30 minutes before stress test and were repeated until 45 minutes after the end of the stress test.'}, {'measure': 'State Anxiety and Stress Perception Measured by STAI-X1', 'timeFrame': '-90 minutes, +15 minutes, +100 minutes', 'description': 'State anxiety and stress perception were measured by State-Trait Anxiety Inventory X1 before and after a stress test. The measurements took place 90 minutes before stress test and were repeated 15 and 100 minutes after the end of the stress test. The German version of the State-Trait-Anxiety Inventory was used and differentiates between temporary/emotional state anxiety versus personality trait anxiety. The two scales with 20 items each assess (1) anxiety as a trait (STAI-X2) and (2) anxiety as a state (STAI-XI). Answers are given in a 4-point rating scale ranging from 1 ="not at all" to 4 ="very true". For analysis of each, STAI-scale single scores were summed up to one total score, representing the state and trait anxiety. Score range is 20-80 and higher scores indicate a higher anxiety.'}, {'measure': 'Psychological Questionnaire (Modified Somatic SCL90)', 'timeFrame': '-210 minutes, +100 minutes', 'description': 'The SCL90 has 90 items with dimensions like depression, somatization, obsessive-compulsive disorder, social insecurity, anxiety, phobic anxiety, aggression/hostility, paranoid ideation, psychoticism and each item in a subscale ranged from 0 to 4. The lower range values are favorable outcomes and higher are worse outcomes. The modified somatic SCL90 uses the SCL90 somatization items, but instead of a 7 day timeframe asks for "now". The corresponding items from SCL90 were: 1, 4, 12, 27, 40, 42, 48, 49, 52, 53, 56, 58 and the introductory question: "How much do you currently suffer from" ("Wie sehr leiden Sie momentan unter:"). The median of the average Modified Somatic SCL90 score is reported. The average score was calculated at each time point as the sum score divided by the number of non-missing individual question results for subjects with no more than 2 missing responses. The lower values in the range represent favorable outcomes while the higher values represent worse outcomes.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['acute stress reaction', 'stress', 'stress perception', 'physiological stress response', 'Neurexan'], 'conditions': ['Acute Stress Reaction']}, 'referencesModule': {'references': [{'pmid': '17615391', 'type': 'BACKGROUND', 'citation': 'McEwen BS. Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev. 2007 Jul;87(3):873-904. doi: 10.1152/physrev.00041.2006.'}, {'pmid': '16952284', 'type': 'BACKGROUND', 'citation': 'Elsenbruch S, Lucas A, Holtmann G, Haag S, Gerken G, Riemenschneider N, Langhorst J, Kavelaars A, Heijnen CJ, Schedlowski M. Public speaking stress-induced neuroendocrine responses and circulating immune cell redistribution in irritable bowel syndrome. Am J Gastroenterol. 2006 Oct;101(10):2300-7. doi: 10.1111/j.1572-0241.2006.00837.x. Epub 2006 Sep 4.'}, {'pmid': '8255414', 'type': 'BACKGROUND', 'citation': "Kirschbaum C, Pirke KM, Hellhammer DH. The 'Trier Social Stress Test'--a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology. 1993;28(1-2):76-81. doi: 10.1159/000119004."}, {'pmid': '21689890', 'type': 'BACKGROUND', 'citation': 'Hellhammer J, Schubert M. The physiological response to Trier Social Stress Test relates to subjective measures of stress during but not before or after the test. Psychoneuroendocrinology. 2012 Jan;37(1):119-24. doi: 10.1016/j.psyneuen.2011.05.012.'}, {'pmid': '19837490', 'type': 'BACKGROUND', 'citation': 'Schult J, Hero T, Hellhammer J. Effects of powdered fertilized eggs on the stress response. Clin Nutr. 2010 Apr;29(2):255-60. doi: 10.1016/j.clnu.2009.09.004. Epub 2009 Oct 17.'}, {'pmid': '4303377', 'type': 'BACKGROUND', 'citation': 'Mason JW. A review of psychoendocrine research on the pituitary-adrenal cortical system. Psychosom Med. 1968 Sep-Oct;30(5):Suppl:576-607. No abstract available.'}, {'pmid': '5535207', 'type': 'BACKGROUND', 'citation': 'Weiss JM. Somatic effects of predictable and unpredictable shock. Psychosom Med. 1970 Jul-Aug;32(4):397-408. doi: 10.1097/00006842-197007000-00008. No abstract available.'}, {'pmid': '10600217', 'type': 'BACKGROUND', 'citation': 'Pawlak CR, Jacobs R, Mikeska E, Ochsmann S, Lombardi MS, Kavelaars A, Heijnen CJ, Schmidt RE, Schedlowski M. Patients with systemic lupus erythematosus differ from healthy controls in their immunological response to acute psychological stress. Brain Behav Immun. 1999 Dec;13(4):287-302. doi: 10.1006/brbi.1999.0553.'}, {'pmid': '8598500', 'type': 'BACKGROUND', 'citation': 'Schedlowski M, Hosch W, Oberbeck R, Benschop RJ, Jacobs R, Raab HR, Schmidt RE. Catecholamines modulate human NK cell circulation and function via spleen-independent beta 2-adrenergic mechanisms. J Immunol. 1996 Jan 1;156(1):93-9.'}, {'pmid': '9491439', 'type': 'BACKGROUND', 'citation': 'Schmid-Ott G, Jacobs R, Jager B, Klages S, Wolf J, Werfel T, Kapp A, Schurmeyer T, Lamprecht F, Schmidt RE, Schedlowski M. Stress-induced endocrine and immunological changes in psoriasis patients and healthy controls. A preliminary study. Psychother Psychosom. 1998;67(1):37-42. doi: 10.1159/000012257.'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to explore the efficacy of acutely dosed Neurexan using an experimental stress test called the Trier Social Stress Test', 'detailedDescription': 'An acute stress reaction is a biopsychological condition arising in response to an event which is individually regarded as emotionally stressful. The onset of a stress response is associated with specific physiological actions in the sympathetic nervous system, both directly and indirectly through the release of adrenaline and to a lesser extent noradrenaline from the medulla of the adrenal glands. These catecholamine hormones facilitate immediate physical reactions by triggering increases in heart rate and breathing, constricting blood vessels. The other major player in the acute stress response is the hypothalamic-pituitary-adrenal axis.\n\nAlthough stress has been described as a non-specific psychophysiological response to environmental stimuli, it is possible to discern specific bodily stress responses caused by specific emotional reactions to novel, ambivalent or uncontrollable situations and stimuli. For example, social stress induces elevated cortisol levels, particularly if the stressor is uncontrollable, unpredictable, and constitutes a social-evaluative threat due to the judgment of others such as in the Trier Social Stress Test). Usually, the TSST induces a two-fold increase in saliva cortisol with peaks around 10-20 min. after stress test termination. Also, an average increase in heart rates of around 20 beats per minute (bpm) is observed during the TSST. In addition, emotional states and feelings have been shown to be affected by this stress test, such as marked increases in stress perception,anxiety and emotional insecurity as well as decreases in mood, calmness and feeling awake.\n\nPreliminary results indicate that Neurexan® may improve coping abilities in stressful situations. This study aims to investigate the effect of Neurexan® on subjectively perceived nervousness and tension during an acute stressful situation and to characterize the efficacy profile of Neurexan®.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '59 Years', 'minimumAge': '31 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Provide written informed consent\n2. Healthy male or female\n3. age between 31 to 59 years\n4. Fluent in German language.\n5. Ability to understand the explanations and instructions given by the study physician\n\nExclusion Criteria:\n\n1. allergies to ingredients of Neurexan® (Passiflora incarnata, Avena sativa, Coffea arabica, Zincum isovalerianicum, lactose monohydrate, magnesium stearate)\n2. lactose intolerance\n3. use of any psychological stress-management intervention within the last 4 weeks\n4. sick leave for any reason\n5. participation in any other clinical study 3 months prior to Screening Visit\n6. current or recent (3 months prior to Screening Visit) history of substance abuse or drug dependence including nicotine and alcohol (as verified in the respective IDCL list)\n7. smokers\n8. alcohol intake within last 24 hours (before Baseline Visit V3)\n9. shift workers or work regularly during night time\n10. use of any psychotropic medication or suffering from severe psychiatric illness needing acute intervention\n11. BMI \\> 30 kg/m2\n12. currently pregnant (verified by urine pregnancy test) or lactating\n13. participation in a previous TSST study\n14. high chronic stress as verified with the TICS-SSCS (a score of ≥ 23 on the screening scale for chronic stress meets the criterion of being chronically stressed)\n15. major mental disorder as verified with the IDCL (depressive episode, panic disorder, social phobia, obsessive-compulsory disorder; alcohol dependency; schizophrenia and mania.)\n16. employee of the Sponsor, one of the investigators or the CRO\n17. use of any concomitant medication except contraceptives\n18. any somatic disease or other condition the Investigator or their duly assigned representatives believes may affect the ability of the individual to complete the study or the interpretation of the study results\n19. Individuals whose ability to speak for themselves lacks or can be doubted'}, 'identificationModule': {'nctId': 'NCT01703832', 'acronym': 'NEUPRO-OL', 'briefTitle': 'Explorative Open Label Study of Efficacy Profile of Neurexan® in Experimental Acute Stress Setting in Healthy Subjects', 'organization': {'class': 'INDUSTRY', 'fullName': 'Biologische Heilmittel Heel GmbH'}, 'officialTitle': 'Efficacy Profile of Neurexan® in an Experimental Acute Stress Setting - an Explorative Open-Label Study in Healthy Probands', 'orgStudyIdInfo': {'id': 'C1202'}, 'secondaryIdInfos': [{'id': '2012-002359-40', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Neurexan®', 'description': '0.6 mg / tablet, 6 tablets, 1 tablet every 30 minutes from -180 minutes to -30 minutes', 'interventionNames': ['Drug: Neurexan®']}, {'type': 'NO_INTERVENTION', 'label': 'No intervention', 'description': 'no tablet intake and subjects will undergo the natural course'}], 'interventions': [{'name': 'Neurexan®', 'type': 'DRUG', 'description': '0.6 mg / tablet, 6 tablets, 1 tablet every 30 minutes from -180 minutes to -30 minutes', 'armGroupLabels': ['Neurexan®']}]}, 'contactsLocationsModule': {'locations': [{'zip': '45122', 'city': 'Essen', 'country': 'Germany', 'facility': 'Institut fur Medizinische Psychologie und Verhaltensimmunbiologie Universitatsklinikum Essen', 'geoPoint': {'lat': 51.45657, 'lon': 7.01228}}, {'zip': '35032', 'city': 'Marburg', 'country': 'Germany', 'facility': 'Klinische Psychologie und Psychotherapie, Fachbereich Psychologie, Universität Marburg', 'geoPoint': {'lat': 50.80904, 'lon': 8.77069}}], 'overallOfficials': [{'name': 'Manfred Schedlowski, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Institut für Medizinische und Verhaltensimmunbiologie Universitätsklinikum Essen'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Biologische Heilmittel Heel GmbH', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}