Ignite Creation Date:
2025-12-25 @ 4:29 AM
Ignite Modification Date:
2025-12-26 @ 3:32 AM
Study NCT ID:
NCT01378520
Status:
COMPLETED
Last Update Posted:
2018-06-01
First Post:
2011-06-16
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Effect of Ketoconazole on Breathlessness
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D029424', 'term': 'Pulmonary Disease, Chronic Obstructive'}, {'id': 'D004417', 'term': 'Dyspnea'}], 'ancestors': [{'id': 'D008173', 'term': 'Lung Diseases, Obstructive'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D012120', 'term': 'Respiration Disorders'}, {'id': 'D012818', 'term': 'Signs and Symptoms, Respiratory'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D007654', 'term': 'Ketoconazole'}, {'id': 'D000935', 'term': 'Antifungal Agents'}], 'ancestors': [{'id': 'D010879', 'term': 'Piperazines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D000890', 'term': 'Anti-Infective Agents'}, {'id': 'D045506', 'term': 'Therapeutic Uses'}, {'id': 'D020228', 'term': 'Pharmacologic Actions'}, {'id': 'D020164', 'term': 'Chemical Actions and Uses'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'Donald.a.mahler@hitchcock.org', 'phone': '603 650-5533', 'title': 'Donald A. Mahler, M.D.', 'organization': 'Dartmouth-Hitchcock'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'Ketoconazole', 'description': 'Ketoconazole(600 mg taken orally)', 'otherNumAtRisk': 10, 'otherNumAffected': 0, 'seriousNumAtRisk': 10, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Inert Powder', 'description': 'Inert powder (in capsule taken orally)', 'otherNumAtRisk': 10, 'otherNumAffected': 0, 'seriousNumAtRisk': 10, 'seriousNumAffected': 0}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Unpleasantness of Breathlessness', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '20', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ketoconazole', 'description': 'Ketoconazole (600 mg given orally)'}, {'id': 'OG001', 'title': 'Inert Powder', 'description': 'Inert powder (in capsule taken orally)'}], 'classes': [{'categories': [{'measurements': [{'value': '72.5', 'spread': '23.8', 'groupId': 'OG000'}, {'value': '72.6', 'spread': '23.5', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'At 1 minute intervals during Resistive Load Breathing at Period 1 (Day 3 or 4) and Period 2 (Day 5, 6 or 7)', 'description': 'The average of all ratings for the unpleasantness of breathlessness at equivalent times for each subject during Resistive Load Breathing (RLB). For example, if 1 subject provided 6 ratings during 6 minutes of RLB with Ketoconazole and 10 ratings during 10 minutes of RLB with inert powder, then ratings for unpleasantness through 6 minutes were used for analysis for that patient. This approach was used for all subjects to yield a total of 252 ratings for Ketoconazole and for inert powder.\n\nSubject rating of intensity of unpleasantness was obtained during RLB on a 100 mm Visual Analog Scale anchored at the bottom by "No Unpleasantness" and at the top by "Greatest Unpleasantness".', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'PRIMARY', 'title': 'Intensity of Breathlessness', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '20', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ketoconazole', 'description': 'Ketoconazole (600 mg given orally)'}, {'id': 'OG001', 'title': 'Inert Powder', 'description': 'Inert powder (in capsule taken orally)'}], 'classes': [{'categories': [{'measurements': [{'value': '77.6', 'spread': '22.3', 'groupId': 'OG000'}, {'value': '78.2', 'spread': '21.4', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'At 1 minute intervals during Resistive Load Breathing at Period 1 (Day 3 or 4) and Period 2 (Day 5, 6 or 7)', 'description': 'The average of all ratings for the intensity of breathlessness at equivalent times for each subject during Resistive Load Breathing (RLB). For example, if 1 subject provided 6 ratings during 6 minutes of RLB with Ketoconazole and 10 ratings during 10 minutes of RLB with inert powder, then ratings for intensity through 6 minutes were used for analysis for that patient. This approach was used for all subjects to yield a total of 252 ratings for Ketoconazole and for inert powder.\n\nSubject rating of intensity of breathlessness was obtained at 1 minute intervals during RLB on a 100 mm Visual Analog Scale anchored at the bottom by "No Intensity" and at the top by "Greatest Intensity".', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Level of B-endorphin Immunoreactivity', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '20', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ketoconazole', 'description': 'Ketoconazole (600 mg given orally)'}, {'id': 'OG001', 'title': 'Inert Powder', 'description': 'Inert powder (in capsule taken orally)'}], 'classes': [{'categories': [{'measurements': [{'value': '153.9', 'spread': '18.0', 'groupId': 'OG000'}, {'value': '93.9', 'spread': '7.9', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'At the end of resistance load breathing (4.5 hours after receiving the test article)', 'description': 'Change between pre-treatment and post treatment serum levels of beta-endorphin immunoreactivity measured in pmol/L', 'unitOfMeasure': 'pmol/L', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'First Ketoconazole, Then Inert Powder', 'description': 'Ketoconzaole (600 mg taken orally) in first intervention period and inert powder (in capsule taken orally) in second intervention period.'}, {'id': 'FG001', 'title': 'First Inert Powder, Then Ketoconazole', 'description': 'Inert powder (in capsule taken orally) in first intervention period and Ketoconzaole (600 mg taken orally) in second intervention period.'}], 'periods': [{'title': 'First Intervention (Day 2-3)', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}, {'groupId': 'FG001', 'numSubjects': '10'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}, {'groupId': 'FG001', 'numSubjects': '10'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}, {'title': 'Second Intervention (Day 4-6)', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}, {'groupId': 'FG001', 'numSubjects': '10'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}, {'groupId': 'FG001', 'numSubjects': '10'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'June 2011 - January 2012; medical center', 'preAssignmentDetails': '23 subjects recruited; 1 excluded (did not meet inclusion/exclusion criteria); 2 withdrawn prior to randomization (1 could not tolerate breathing through the initial inspiratory resistance (15 cm H 2 O/L/s); 1 gave ratings of breathlessness of \\< 50 mm on the VAS for the highest resistance (50 cm H2O/L/s))'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Entire Study Population', 'description': 'Includes groups randomized to receive Ketoconazole first and inert powder first.'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '69.6', 'spread': '6.9', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '10', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '10', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '20', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 20}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2011-06'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-05', 'completionDateStruct': {'date': '2012-02', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2018-05-04', 'studyFirstSubmitDate': '2011-06-16', 'resultsFirstSubmitDate': '2013-09-11', 'studyFirstSubmitQcDate': '2011-06-21', 'lastUpdatePostDateStruct': {'date': '2018-06-01', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2013-09-11', 'studyFirstPostDateStruct': {'date': '2011-06-22', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2013-11-14', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2012-02', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Unpleasantness of Breathlessness', 'timeFrame': 'At 1 minute intervals during Resistive Load Breathing at Period 1 (Day 3 or 4) and Period 2 (Day 5, 6 or 7)', 'description': 'The average of all ratings for the unpleasantness of breathlessness at equivalent times for each subject during Resistive Load Breathing (RLB). For example, if 1 subject provided 6 ratings during 6 minutes of RLB with Ketoconazole and 10 ratings during 10 minutes of RLB with inert powder, then ratings for unpleasantness through 6 minutes were used for analysis for that patient. This approach was used for all subjects to yield a total of 252 ratings for Ketoconazole and for inert powder.\n\nSubject rating of intensity of unpleasantness was obtained during RLB on a 100 mm Visual Analog Scale anchored at the bottom by "No Unpleasantness" and at the top by "Greatest Unpleasantness".'}, {'measure': 'Intensity of Breathlessness', 'timeFrame': 'At 1 minute intervals during Resistive Load Breathing at Period 1 (Day 3 or 4) and Period 2 (Day 5, 6 or 7)', 'description': 'The average of all ratings for the intensity of breathlessness at equivalent times for each subject during Resistive Load Breathing (RLB). For example, if 1 subject provided 6 ratings during 6 minutes of RLB with Ketoconazole and 10 ratings during 10 minutes of RLB with inert powder, then ratings for intensity through 6 minutes were used for analysis for that patient. This approach was used for all subjects to yield a total of 252 ratings for Ketoconazole and for inert powder.\n\nSubject rating of intensity of breathlessness was obtained at 1 minute intervals during RLB on a 100 mm Visual Analog Scale anchored at the bottom by "No Intensity" and at the top by "Greatest Intensity".'}], 'secondaryOutcomes': [{'measure': 'Change in Level of B-endorphin Immunoreactivity', 'timeFrame': 'At the end of resistance load breathing (4.5 hours after receiving the test article)', 'description': 'Change between pre-treatment and post treatment serum levels of beta-endorphin immunoreactivity measured in pmol/L'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['breathlessness', 'resistive load breathing', 'beta-endorphins'], 'conditions': ['Chronic Obstructive Pulmonary Disease']}, 'referencesModule': {'references': [{'pmid': '21513438', 'type': 'BACKGROUND', 'citation': 'Gifford AH, Mahler DA, Waterman LA, Ward J, Kraemer WJ, Kupchak BR, Baird JC. Neuromodulatory effect of endogenous opioids on the intensity and unpleasantness of breathlessness during resistive load breathing in COPD. COPD. 2011 Jun;8(3):160-6. doi: 10.3109/15412555.2011.560132. Epub 2011 Apr 22.'}, {'pmid': '23715032', 'type': 'DERIVED', 'citation': 'Mahler DA, Gifford AH, Waterman LA, Ward J, Kraemer WJ, Kupchak BR, Harver A. Effect of increased blood levels of beta-endorphin on perception of breathlessness. Chest. 2013 May;143(5):1378-1385. doi: 10.1378/chest.12-1541.'}]}, 'descriptionModule': {'briefSummary': 'Beta-endorphins, which are naturally occurring narcotic substances, have been shown to alter the perception of breathlessness. Oral ketoconazole, an antifungal antibiotic, increases blood levels of beta-endorphins. The study hypothesis is that oral ketoconazole will reduce ratings of breathlessness induced by resistive breathing loads.', 'detailedDescription': "Beta-endorphins are naturally occurring narcotic substances (like morphine) that are released by the brain under stressful conditions, such as exercise and when breathing through a resistive load (a tube containing fine wire mesh). In one study of 8 patients with coronary artery disease, ketoconazole, an oral medication used to treat fungal infections, was administered (1,200 mg at 12 midnight and 600 mg at 6 am) and increased blood levels of beta-endorphins five fold. In a recent study performed at Dartmouth-Hitchcock Medical Center, we found that ketoconazole increased blood levels of beta-endorphins in all eight patients with chronic obstructive pulmonary disease (COPD). Mean values increased by 2.5 times at four hours compared with baseline values (p = 0.0078). Based on this significant response, we propose to study the effect of ketoconazole on patients' perception of breathlessness induced by resistive breathing loads in a randomized clinical trial. The hypothesis of the study is that ketoconazole will reduce ratings of breathlessness as mediated by the increased levels of beta-endorphins."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '50 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* 50 years of age or older;\n* diagnosis of COPD;\n* current or former smoker of at least 10 pack-years;\n* post-bronchodilator FEV1 greater than or equal to 30% predicted and less than or equal to 80% predicted; post-bronchodilator ratio \\< 70%\n\nExclusion Criteria:\n\n* any concomitant disease that might interfere with study procedures;\n* use of a drug that may cause a possible drug interaction with ketoconazole'}, 'identificationModule': {'nctId': 'NCT01378520', 'acronym': 'KetoRLB', 'briefTitle': 'Effect of Ketoconazole on Breathlessness', 'organization': {'class': 'OTHER', 'fullName': 'Dartmouth-Hitchcock Medical Center'}, 'officialTitle': 'The Effect of Ketoconazole on Breathlessness During Resistive Load Breathing in Patients With Chronic Obstructive Pulmonary Disease', 'orgStudyIdInfo': {'id': 'CPHS22775'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'ketoconazole', 'description': '600 mg ketoconazole', 'interventionNames': ['Drug: ketoconazole']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'inert powder', 'description': 'inert powder in capsule', 'interventionNames': ['Drug: inert powder']}], 'interventions': [{'name': 'ketoconazole', 'type': 'DRUG', 'otherNames': ['oral antifungal'], 'description': '600 mg capsule oral once', 'armGroupLabels': ['ketoconazole']}, {'name': 'inert powder', 'type': 'DRUG', 'otherNames': ['oral placebo'], 'description': 'oral once', 'armGroupLabels': ['inert powder']}]}, 'contactsLocationsModule': {'locations': [{'zip': '03756-0001', 'city': 'Lebanon', 'state': 'New Hampshire', 'country': 'United States', 'facility': 'Dartmouth-Hitchcock Medical Center', 'geoPoint': {'lat': 43.64229, 'lon': -72.25176}}], 'overallOfficials': [{'name': 'Donald A Mahler, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Dartmouth-Hitchcock Medical Center'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Dartmouth-Hitchcock Medical Center', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}