Ignite Creation Date:
2025-12-25 @ 3:09 AM
Ignite Modification Date:
2026-02-25 @ 10:04 PM
Study NCT ID:
NCT03746405
Status:
COMPLETED
Last Update Posted:
2020-12-10
First Post:
2018-11-16
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Effects of Connectivity-based rTMS and State-Dependency on Amygdala Activation
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D050781', 'term': 'Transcranial Magnetic Stimulation'}], 'ancestors': [{'id': 'D055909', 'term': 'Magnetic Field Therapy'}, {'id': 'D013812', 'term': 'Therapeutics'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'lysianne.beynel@duke.edu', 'phone': '919-681-1157', 'title': 'Dr Lysianne Beynel', 'organization': 'Duke University'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': 'during rTMS application, and up to one hour after.', 'eventGroups': [{'id': 'EG000', 'title': 'Repetitive TMS (rTMS)', 'description': 'excitatory rTMS applied over the medial prefrontal cortex (fMRI-guided)\n\nrepetitive transcranial magnetic stimulation: excitatory 5Hz rTMS will be used', 'otherNumAtRisk': 7, 'deathsNumAtRisk': 7, 'otherNumAffected': 0, 'seriousNumAtRisk': 7, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Sham Repetitive TMS (rTMS)', 'description': 'electrical sham coil applied over the medial prefrontal cortex (fMRI-guided)\n\nSham repetitive transcranial magnetic stimulation: an electrical sham coil reproducing the same clicking sound and tactile sensation than the active rTMS will be used', 'otherNumAtRisk': 6, 'deathsNumAtRisk': 6, 'otherNumAffected': 0, 'seriousNumAtRisk': 6, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Acute Effect of a rTMS Session on Brain Activation as Measured by the Cerebral Blood Flow (Blood Oxygenation Level Dependent Signal)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Repetitive TMS (rTMS)', 'description': 'excitatory rTMS applied over the medial prefrontal cortex (fMRI-guided)\n\nrepetitive transcranial magnetic stimulation: excitatory 5Hz rTMS will be used'}, {'id': 'OG001', 'title': 'Sham Repetitive TMS (rTMS)', 'description': 'electrical sham coil applied over the medial prefrontal cortex (fMRI-guided)\n\nSham repetitive transcranial magnetic stimulation: an electrical sham coil reproducing the same clicking sound and tactile sensation than the active rTMS will be used'}], 'classes': [{'categories': [{'measurements': [{'value': '0.67', 'spread': '0.48', 'groupId': 'OG000'}, {'value': '-0.48', 'spread': '0.87', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '= 0.03', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'paramValue': '1.15', 'pValueComment': 'Give the limited sample size, this p-value was not adjusted for multiple comparisons. The threshold for statistical significant was p \\< 0.05', 'groupDescription': 'Hypothesis: Active rTMS applied over the node in the medial prefrontal cortex the most strongly negatively connected to the right amygdala will decrease amygdala BOLD activation compared to sham rTMS', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'right after the rTMS session, up to one hour', 'description': 'Blood oxygenation level dependent (BOLD) will be assessed to evaluate the acute effect of rTMS applied over the medial prefrontal cortex on the amygdala activation.\n\nThis outcome (expressed a z-score) represents the amygdala activation, either after active rTMS or after sham rTMS.\n\nHigher z-scores for active than for sham rTMS indicates that amygdala activity increases after active rTMS compared to sham rTMS, on the other hand lower z-score after active rTMS vs. after Sham rTMS indicated that the amygdala activity would have been reduced with active rTMS.', 'unitOfMeasure': 'z score in the amygdala', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who completed the study'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Repetitive TMS (rTMS)', 'description': 'excitatory rTMS applied over the medial prefrontal cortex (fMRI-guided)\n\nrepetitive transcranial magnetic stimulation: excitatory 5Hz rTMS will be used'}, {'id': 'FG001', 'title': 'Sham Repetitive TMS (rTMS)', 'description': 'electrical sham coil applied over the medial prefrontal cortex (fMRI-guided)\n\nSham repetitive transcranial magnetic stimulation: an electrical sham coil reproducing the same clicking sound and tactile sensation than the active rTMS will be used'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'comment': 'Seven subjects were excluded before the second visit (when rTMS occured) and therefore were not randomized in the active or the sham group', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}, {'groupId': 'FG001', 'numSubjects': '8'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '7'}, {'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '2'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'technical difficulties', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '2'}]}]}], 'preAssignmentDetails': 'Across the 25 enrolled participants, 7 were excluded after the first visit for different reasons such as: contraindications, too high resting motor threshold or technical difficulties'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Repetitive TMS (rTMS)', 'description': 'excitatory rTMS applied over the medial prefrontal cortex (fMRI-guided)\n\nrepetitive transcranial magnetic stimulation: excitatory 5Hz rTMS will be used'}, {'id': 'BG001', 'title': 'Sham Repetitive TMS (rTMS)', 'description': 'electrical sham coil applied over the medial prefrontal cortex (fMRI-guided)\n\nSham repetitive transcranial magnetic stimulation: an electrical sham coil reproducing the same clicking sound and tactile sensation than the active rTMS will be used'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'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': '10', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'calculatePct': False, 'unitOfMeasure': 'Participants'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '7', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '11', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '7', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race/Ethnicity, Customized', 'classes': [{'title': 'Ethnicity', 'categories': [{'title': 'African American', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}, {'title': 'Asian', 'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}]}, {'title': 'White', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '5', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '10', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': 'Participants who were randomized in the active or sham group.'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2019-02-14', 'size': 787601, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2020-10-08T13:37', 'hasProtocol': True}, {'date': '2019-02-14', 'size': 243096, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2020-10-08T13:41', 'hasProtocol': False}, {'date': '2020-02-10', 'size': 355768, 'label': 'Informed Consent Form', 'hasIcf': True, 'hasSap': False, 'filename': 'ICF_002.pdf', 'typeAbbrev': 'ICF', 'uploadDate': '2020-10-08T13:47', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['PARTICIPANT']}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 25}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2019-06-16', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-12', 'completionDateStruct': {'date': '2020-01-31', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-12-09', 'studyFirstSubmitDate': '2018-11-16', 'resultsFirstSubmitDate': '2020-10-09', 'studyFirstSubmitQcDate': '2018-11-16', 'lastUpdatePostDateStruct': {'date': '2020-12-10', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2020-10-09', 'studyFirstPostDateStruct': {'date': '2018-11-19', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2020-11-05', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2020-01-31', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Acute Effect of a rTMS Session on Brain Activation as Measured by the Cerebral Blood Flow (Blood Oxygenation Level Dependent Signal)', 'timeFrame': 'right after the rTMS session, up to one hour', 'description': 'Blood oxygenation level dependent (BOLD) will be assessed to evaluate the acute effect of rTMS applied over the medial prefrontal cortex on the amygdala activation.\n\nThis outcome (expressed a z-score) represents the amygdala activation, either after active rTMS or after sham rTMS.\n\nHigher z-scores for active than for sham rTMS indicates that amygdala activity increases after active rTMS compared to sham rTMS, on the other hand lower z-score after active rTMS vs. after Sham rTMS indicated that the amygdala activity would have been reduced with active rTMS.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': True}, 'conditionsModule': {'conditions': ['Amygdala Activation']}, 'descriptionModule': {'briefSummary': 'Posttraumatic stress disorder (PTSD) is a highly debilitating disease with response rates to pharmacological treatment rarely exceeding 60%. Preliminary attempts have been made to use repetitive transcranial magnetic stimulation (rTMS) as a non-pharmacological treatment alternative, but thus far rTMS approaches have demonstrated only modest efficacy. A major factor contributing to these limited effects stems from the depth penetration of TMS, which is not sufficient to directly modulate deep subcortical structures, such as the amygdala, that are affected in PTSD. Moreover, while rTMS effects have been shown to be state-dependent, (i.e. vary substantially according to the neural state during stimulation), this important factor is rarely considered during the clinical application of rTMS. The current study addresses both of these limitations to improve the therapeutic efficacy of rTMS for PTSD. Here we will develop a protocol to test if connectivity-based rTMS is able to modulate amygdala activity through the functional connections with medial prefrontal cortex, taking advantage of state-dependency to enhance rTMS effects by actively engaging the amygdala through a fear perception task. BOLD activation in the amygdala and its connectivity with the frontal cortex will constitute the primary outcomes to test rTMS efficacy. Heart rate variability and skin galvanic responses, acquired during the presentation of fearful faces, will be used as continuous moderators of task engagement during rTMS. If successful, this study will pave the way for a large-scale study to investigate whether state-dependent, connectivity-based rTMS of the amygdala can improve rTMS efficacy as a clinical treatment for PTSD.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '35 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age Restrictions: Young Group (from 18 to 35 years old)\n* Use of effective method of birth control for women of childbearing capacity.\n* Willing to provide informed consent.\n\nExclusion Criteria:\n\n* Current or recent (within the past 6 months) history of substance abuse or dependence.\n* Current serious medical illness.\n* History of seizure, epilepsy, stroke, brain surgery, head injury, cranial metal implants, known structural brain lesion, devices that may be affected by rTMS or MRI (pacemaker, medication pump, cochlear implant, implanted brain stimulator)\n* Inability or unwilling to give informed consent.\n* Diagnosed any Axis I DSM-IV disorder (MINI, DSM-IV).\n* Clinically defined neurological disorder.\n* Increased risk of seizure for any reason, including prior diagnosis of increased intracranial pressure, or currently taking medication that lowers the seizure threshold.\n* Claustrophobia (MRI scanner).\n* Pregnancy.'}, 'identificationModule': {'nctId': 'NCT03746405', 'acronym': 'ConnecTMS', 'briefTitle': 'Effects of Connectivity-based rTMS and State-Dependency on Amygdala Activation', 'organization': {'class': 'OTHER', 'fullName': 'Duke University'}, 'officialTitle': 'Effects of Connectivity-based rTMS and State-Dependency on Amygdala Activation', 'orgStudyIdInfo': {'id': 'Pro00101172'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Repetitive TMS (rTMS)', 'description': 'excitatory rTMS applied over the medial prefrontal cortex (fMRI-guided)', 'interventionNames': ['Device: repetitive transcranial magnetic stimulation']}, {'type': 'SHAM_COMPARATOR', 'label': 'Sham repetitive TMS (rTMS)', 'description': 'electrical sham coil applied over the medial prefrontal cortex (fMRI-guided)', 'interventionNames': ['Device: Sham repetitive transcranial magnetic stimulation']}], 'interventions': [{'name': 'repetitive transcranial magnetic stimulation', 'type': 'DEVICE', 'description': 'excitatory 5Hz rTMS will be used', 'armGroupLabels': ['Repetitive TMS (rTMS)']}, {'name': 'Sham repetitive transcranial magnetic stimulation', 'type': 'DEVICE', 'description': 'an electrical sham coil reproducing the same clicking sound and tactile sensation than the active rTMS will be used', 'armGroupLabels': ['Sham repetitive TMS (rTMS)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '27705', 'city': 'Durham', 'state': 'North Carolina', 'country': 'United States', 'facility': 'Duke University Medical Center', 'geoPoint': {'lat': 35.99403, 'lon': -78.89862}}], 'overallOfficials': [{'name': 'Lysianne Beynel, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Duke University'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Duke University', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}