Ignite Creation Date:
2025-12-24 @ 8:03 PM
Ignite Modification Date:
2026-03-20 @ 9:43 AM
Study NCT ID:
NCT03845504
Status:
TERMINATED
Last Update Posted:
2023-12-12
First Post:
2019-02-15
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
iTBS in Refractory Pediatric Depression
Sponsor:
Organization:
Raw JSON
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The CDRS-R total score is the sum of the responses to 17 questions. Each question is graded on a 5- or 7-point scale. Total score ranges from 17-113. In general, higher values of CDRS-R total score represent greater severity of illness. Response to treatment is determined by a ≥ 50% reduction in score from baseline to end of treatment.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Hamilton Depression Rating Scale (HDRS-17)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Intermittent Theta Burst Stimulation', 'description': 'Daily open-label sessions delivered to left DLPFC over up to 6 weeks using the MagVenture MagPro rTMS Research System.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '25.5', 'spread': '0.7', 'groupId': 'OG000'}]}]}, {'title': 'Change at week 6', 'categories': [{'measurements': [{'value': '-11.5', 'spread': '7.8', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and week 6', 'description': 'Standardized assessment to determine depression severity. HDRS-17, a clinician-rated measure of depressive symptoms that consists of 17 items rated using a semi-structured interview. Eight of the 17 HDRS-17 items are rated on a 5-point scale (0=absent; 1=doubtful or mild; 2=mild to moderate; 3=moderate to severe; 4=very severe), while the remaining 9 items are rated on a 3-point scale (0=absent; 1=doubtful or mild; 2=clearly present), yielding a minimum total score of 0 (least severe) and a maximum score of 52 (most severe). Response to treatment is determined by a ≥ 50% reduction in score from baseline to end of treatment.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Intermittent Theta Burst Stimulation', 'description': 'Daily open-label sessions delivered to left dorsolateral prefrontal cortex (DLPFC) over up to 6 weeks using the MagVenture MagPro repetitive transcranial magnetic stimulation (rTMS) Research System.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}], 'preAssignmentDetails': '4 participants were screened for eligibility, 2 were assigned to the study arm.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Intermittent Theta Burst Stimulation', 'description': 'Daily open-label sessions delivered to left DLPFC over up to 6 weeks using the MagVenture MagPro rTMS Research System.'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2020-10-27', 'size': 1710275, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2023-11-10T20:47', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 4}}, 'statusModule': {'whyStopped': 'Staffing not available', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2018-11-19', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-11', 'completionDateStruct': {'date': '2019-10-09', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-11-17', 'studyFirstSubmitDate': '2019-02-15', 'resultsFirstSubmitDate': '2023-11-17', 'studyFirstSubmitQcDate': '2019-02-15', 'lastUpdatePostDateStruct': {'date': '2023-12-12', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2023-11-17', 'studyFirstPostDateStruct': {'date': '2019-02-19', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2023-12-12', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-10-09', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': "Change in Children's Depression Rating Scale - Revised (CDRS-R) Score From", 'timeFrame': 'Baseline and week 6', 'description': 'Standardized assessment to determine depression severity. The CDRS-R total score is the sum of the responses to 17 questions. Each question is graded on a 5- or 7-point scale. Total score ranges from 17-113. In general, higher values of CDRS-R total score represent greater severity of illness. Response to treatment is determined by a ≥ 50% reduction in score from baseline to end of treatment.'}], 'secondaryOutcomes': [{'measure': 'Change in Hamilton Depression Rating Scale (HDRS-17)', 'timeFrame': 'Baseline and week 6', 'description': 'Standardized assessment to determine depression severity. HDRS-17, a clinician-rated measure of depressive symptoms that consists of 17 items rated using a semi-structured interview. Eight of the 17 HDRS-17 items are rated on a 5-point scale (0=absent; 1=doubtful or mild; 2=mild to moderate; 3=moderate to severe; 4=very severe), while the remaining 9 items are rated on a 3-point scale (0=absent; 1=doubtful or mild; 2=clearly present), yielding a minimum total score of 0 (least severe) and a maximum score of 52 (most severe). Response to treatment is determined by a ≥ 50% reduction in score from baseline to end of treatment.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isUnapprovedDevice': True, 'isFdaRegulatedDevice': True}, 'conditionsModule': {'keywords': ['depression', 'transcranial magnetic stimulation', 'adolescent', 'treatment refractory'], 'conditions': ['Depression']}, 'referencesModule': {'references': [{'pmid': '29726344', 'type': 'BACKGROUND', 'citation': 'Blumberger DM, Vila-Rodriguez F, Thorpe KE, Feffer K, Noda Y, Giacobbe P, Knyahnytska Y, Kennedy SH, Lam RW, Daskalakis ZJ, Downar J. Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Lancet. 2018 Apr 28;391(10131):1683-1692. doi: 10.1016/S0140-6736(18)30295-2. Epub 2018 Apr 26.'}, {'pmid': '25165441', 'type': 'BACKGROUND', 'citation': 'Oberman LM, Pascual-Leone A, Rotenberg A. Modulation of corticospinal excitability by transcranial magnetic stimulation in children and adolescents with autism spectrum disorder. Front Hum Neurosci. 2014 Aug 13;8:627. doi: 10.3389/fnhum.2014.00627. eCollection 2014.'}, {'pmid': '26849202', 'type': 'BACKGROUND', 'citation': 'Wall CA, Croarkin PE, Maroney-Smith MJ, Haugen LM, Baruth JM, Frye MA, Sampson SM, Port JD. Magnetic Resonance Imaging-Guided, Open-Label, High-Frequency Repetitive Transcranial Magnetic Stimulation for Adolescents with Major Depressive Disorder. J Child Adolesc Psychopharmacol. 2016 Sep;26(7):582-9. doi: 10.1089/cap.2015.0217. Epub 2016 Feb 5.'}, {'pmid': '29274805', 'type': 'BACKGROUND', 'citation': 'Weigand A, Horn A, Caballero R, Cooke D, Stern AP, Taylor SF, Press D, Pascual-Leone A, Fox MD. Prospective Validation That Subgenual Connectivity Predicts Antidepressant Efficacy of Transcranial Magnetic Stimulation Sites. Biol Psychiatry. 2018 Jul 1;84(1):28-37. doi: 10.1016/j.biopsych.2017.10.028. Epub 2017 Nov 10.'}, {'pmid': '29730251', 'type': 'BACKGROUND', 'citation': 'Li CT, Chen MH, Juan CH, Liu RS, Lin WC, Bai YM, Su TP. Effects of prefrontal theta-burst stimulation on brain function in treatment-resistant depression: A randomized sham-controlled neuroimaging study. Brain Stimul. 2018 Sep-Oct;11(5):1054-1062. doi: 10.1016/j.brs.2018.04.014. Epub 2018 Apr 23.'}]}, 'descriptionModule': {'briefSummary': 'This work will mark the first step in understanding the neural targets for rTMS in youth with difficult to treat depressive symptoms, creating benchmarks for optimizing the safety and efficacy of rTMS for pediatric populations through precision targeting, and encourage funding applications for larger sham- controlled randomized clinical studies.', 'detailedDescription': 'Problem Statement: Depression is a global health problem with limited novel and targeted solutions. Currently available interventions (medication and psychotherapy) have failed to provide adequate clinical improvement in 40% of adolescents with depression and only produce remission in 30% of youth. There is a clear need to develop better targeted interventions for this growing population of youth.\n\nSpecific Aims Aim 1: To examine the efficacy of a targeting strategy to optimize repetitive transcranial magnetic stimulation (rTMS) delivered to the left dorsolateral prefrontal cortex (DLPFC) to reduce depressive symptoms in adolescents between 12-17 years of age. Hypothesis 1: Six weeks of open-label daily intermittent theta-burst stimulation (iTBS) sessions delivered to the left DLPFC will be effective at reducing depressive symptoms between baseline and 10- week follow-up. Hypothesis 2: iTBS over left DLPFC will decrease functional connectivity between left DLPFC and subcallosal cingulate cortex (SCC) and will reduce depression-related hyperconnectivity between nodes of the default mode network (DMN). Hypothesis 3: Higher anti-correlation between left DLPFC and SCC and lower cingulate glutamate concentrations will predict better clinical outcome following iTBS.\n\nAim 2: To determine the tolerability of iTBS in adolescents between 12-17 years of age. Hypothesis 1: iTBS will be well tolerated without any more than minimal side effects. Hypothesis 2: iTBS will result in sufficient cortical excitability, as measured by 64-channel-EEG pre, during, and post iTBS, to induce an antidepressant effect but not induce seizures or other adverse events.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '21 Years', 'minimumAge': '12 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* 10 participants ages 12-21 years of age\n* with at least moderate to severe depressive symptoms confirmed by the Children's Depression Rating Scale-Revised (CDRS-R\\>40) or Hamilton Rating Scale for Depression (HRSD-17 ≥ 18)\n* able to commit to protocol schedule and provide Informed consent by a legal guardian and assent by a youth participant\n* have had at least one prior antidepressant treatment failure with adequate dose and duration\n\nExclusion Criteria:\n\n* prior neurological diagnosis (neurodevelopmental disorders, strokes/traumatic brain injuries, brain tumor, epilepsy)\n* contraindications for TMS or MRI e.g. have any implanted metal\n* unstable medical conditions\n* acute suicide risk, defined as an attempt in past 6 months that required medical treatment, or history of ≥2 suicide attempts in the past 12 months, or has a clear cut plan for suicide\n* pregnancy, suspected pregnancy or not on birth control if sexually active; 6) Inability to locate and quantify a motor threshold\n* any factor that the PI determines to be reason for exclusion."}, 'identificationModule': {'nctId': 'NCT03845504', 'briefTitle': 'iTBS in Refractory Pediatric Depression', 'organization': {'class': 'OTHER', 'fullName': 'Stanford University'}, 'officialTitle': 'Evaluating the Efficacy and Tolerability of Targeted Transcranial Magnetic Stimulation in Youth', 'orgStudyIdInfo': {'id': '45848'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Open Label', 'description': 'Open-label rTMS sessions will occur within \\~2 days after the baseline session with daily sessions delivered to left DLPFC over 2-6 weeks.', 'interventionNames': ['Device: Intermittent Theta Burst Stimulation']}], 'interventions': [{'name': 'Intermittent Theta Burst Stimulation', 'type': 'DEVICE', 'description': 'Stimulation will be administered using the MagVenture MagPro rTMS Research System at currently FDA approved parameters (www.magvitatms.com). The TBS parameters will be 3-pulse 50-Hz bursts given every 200 ms (at 5 Hz) and an intensity of 80% active motor threshold, as measured from the right first dorsal interosseous muscle by a hand-held 700-mm figure-of-eight coil. rTMS will be applied for 9 min delivering a total of 1800 pulses/session.', 'armGroupLabels': ['Open Label']}]}, 'contactsLocationsModule': {'locations': [{'zip': '94305', 'city': 'Stanford', 'state': 'California', 'country': 'United States', 'facility': 'Stanford University Pediatric Mood Disorders Program', 'geoPoint': {'lat': 37.42411, 'lon': -122.16608}}], 'overallOfficials': [{'name': 'Manpreet K Singh, MD MS', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Associate Professor'}, {'name': 'Nolan Williams, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Assistant Professor'}, {'name': 'Hugh B Solvason, PhD MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Associate Professor'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'Small pilot study that will be the start of setting up a larger treatment trial that will be publically available. If feasible, results of the pilot study will be published in scientific journals.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Stanford University', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}