Ignite Creation Date:
2025-12-24 @ 7:32 PM
Ignite Modification Date:
2025-12-27 @ 4:24 PM
Study NCT ID:
NCT00419003
Status:
COMPLETED
Last Update Posted:
2019-07-31
First Post:
2007-01-04
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Research Study for Major Depressive Disorder: Investigation of Glutamate Medications
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003865', 'term': 'Depressive Disorder, Major'}], 'ancestors': [{'id': 'D003866', 'term': 'Depressive Disorder'}, {'id': 'D019964', 'term': 'Mood Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077213', 'term': 'Lamotrigine'}, {'id': 'D007649', 'term': 'Ketamine'}, {'id': 'D019782', 'term': 'Riluzole'}], 'ancestors': [{'id': 'D014227', 'term': 'Triazines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D003510', 'term': 'Cyclohexanes'}, {'id': 'D003516', 'term': 'Cycloparaffins'}, {'id': 'D006840', 'term': 'Hydrocarbons, Alicyclic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D013844', 'term': 'Thiazoles'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D052160', 'term': 'Benzothiazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'sjmathew@bcm.edu', 'phone': '7137985439', 'title': 'Dr. Sanjay Mathew', 'organization': 'Baylor College of Medicine'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': "The open-label administration of ketamine limits interpretation of phase 1 results. The sample size was too small to detect moderators and mediators of response. Third,lack of placebo-controlled efficacy data supporting riluzole's use in depression."}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'Riluzole Group', 'description': 'Patients who met enrolment criteria for phase 1 were randomly allocated to lamotrigine or placebo by a permuted block procedure consisting of blocks of two or four patients. The randomization list was created by a biostatistician with no patient contact. Following baseline ratings, 2 h prior to i.v. ketamine infusion, patients received 300 mg lamotrigine or placebo by mouth.', 'otherNumAtRisk': 6, 'otherNumAffected': 6, 'seriousNumAtRisk': 6, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Placebo', 'description': 'Patients who met enrolment criteria for phase 1 were randomly allocated to lamotrigine or placebo by a permuted block procedure consisting of blocks of two or four patients. The randomization list was created by a biostatistician with no patient contact. Following baseline ratings, 2 h prior to i.v. ketamine infusion, patients received 300 mg lamotrigine or placebo by mouth.', 'otherNumAtRisk': 8, 'otherNumAffected': 5, 'seriousNumAtRisk': 8, 'seriousNumAffected': 0}, {'id': 'EG002', 'title': 'Ketamine', 'description': 'IV infusion of 0.5 mg/kg of Ketamine Hydrochloride', 'otherNumAtRisk': 26, 'otherNumAffected': 26, 'seriousNumAtRisk': 26, 'seriousNumAffected': 0}, {'id': 'EG003', 'title': 'Lamotrigine Pre-Treatment', 'description': 'Patients who met enrolment criteria for phase 1 were randomly allocated to lamotrigine or placebo by a permuted block procedure consisting of blocks of two or four patients. The randomization list was created by a biostatistician with no patient contact. Following baseline ratings, 2 h prior to i.v. ketamine infusion, patients received 300 mg lamotrigine or placebo by mouth.', 'otherNumAtRisk': 13, 'otherNumAffected': 5, 'seriousNumAtRisk': 13, 'seriousNumAffected': 0}, {'id': 'EG004', 'title': 'Placebo Pre-Treatment', 'description': 'Patients who met enrolment criteria for phase 1 were randomly allocated to lamotrigine or placebo by a permuted block procedure consisting of blocks of two or four patients. The randomization list was created by a biostatistician with no patient contact. Following baseline ratings, 2 h prior to i.v. ketamine infusion, patients received 300 mg lamotrigine or placebo by mouth.', 'otherNumAtRisk': 13, 'otherNumAffected': 0, 'seriousNumAtRisk': 13, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 6, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 26, 'numAffected': 26}, {'groupId': 'EG003', 'numAtRisk': 13, 'numEvents': 5, 'numAffected': 5}, {'groupId': 'EG004', 'numAtRisk': 13, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Dizziness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 2, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 26, 'numEvents': 26, 'numAffected': 26}, {'groupId': 'EG003', 'numAtRisk': 13, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 13, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 26, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 13, 'numEvents': 5, 'numAffected': 5}, {'groupId': 'EG004', 'numAtRisk': 13, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Montgomery-Asberg Depression Rating Scale (MARDS) Score (Acute Response to IV Ketamine in Patients With Treatment Resistant Major Depression)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}, {'value': '13', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riluzole Group', 'description': 'Patients who responded (n=14) to the ketamine infusion (in either the lamotrigine or placebo pre-treatment groups) were randomized into phase II for treatment with either riluzole or placebo. One patient in the riluzole group was discontinued/withdrew consent before completing the study.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Patients who responded (n=14) to the ketamine infusion (in either the lamotrigine or placebo pre-treatment groups) were randomized into phase II for treatment with either riluzole or placebo.'}], 'classes': [{'categories': [{'measurements': [{'value': '24.4', 'groupId': 'OG000', 'lowerLimit': '15.9', 'upperLimit': '33.0'}, {'value': '22.0', 'groupId': 'OG001', 'lowerLimit': '14.9', 'upperLimit': '29.1'}]}]}], 'paramType': 'MEAN', 'timeFrame': '24 Hours', 'description': 'Montgomery-Asberg Depression Rating Scale, each of the ten items can be scored from 0 (absence of symptoms to 6 most severe) and has a total score range of 0-60. A lower score on a MADRS indicates a less severe depression. The primary outcome for the initial phase of the trial was the 24-h MADRS score, which included all 10 MADRS items.', 'unitOfMeasure': 'scores on a scale', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Efficacy of Lamotrigine in Decreasing IV Ketamine Psychotomimetic Side Effects', 'timeFrame': '24, 48, or 72-hrs', 'description': 'Response rate and side effect differences to IV ketamine infusion based on lamotrigine and placebo pretreatment groups', 'reportingStatus': 'NOT_POSTED', 'denomUnitsSelected': 'Participants'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Lamotrigine Pre-Treatment (Phase I)/Riluzole (Phase II)', 'description': 'Patients who met enrolment criteria for phase 1 were randomly allocated to lamotrigine or placebo by a permuted block procedure consisting of blocks of two or four patients. The randomization list was created by a biostatistician with no patient contact. Following baseline ratings, 2 h prior to i.v. ketamine infusion, patients received 300 mg lamotrigine or placebo by mouth. All non responders were exited from the study. All responders (in both the lamotrigine and placebo pre-treatment groups were treated as one group and randomized into either treatment with riluzole or placebo for Phase II)'}, {'id': 'FG001', 'title': 'Placebo Pre-Treatment (Phase I)/Placebo (Phase II)', 'description': 'Patients who met enrolment criteria for phase 1 were randomly allocated to lamotrigine or placebo by a permuted block procedure consisting of blocks of two or four patients. The randomization list was created by a biostatistician with no patient contact. Following baseline ratings, 2 h prior to i.v. ketamine infusion, patients received 300 mg lamotrigine or placebo by mouth. All non responders were exited from the study. All responders (in both the lamotrigine and placebo pre-treatment groups were treated as one group and randomized into either treatment with riluzole or placebo for Phase II)'}], 'periods': [{'title': 'Phase I, Ketamine Infusion', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '13'}, {'groupId': 'FG001', 'numSubjects': '13'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '7'}, {'groupId': 'FG001', 'numSubjects': '7'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '6'}]}], 'dropWithdraws': [{'type': 'Lack of Efficacy', 'reasons': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '6'}]}]}, {'title': 'Phase 2, Riluzole/Placebo Follow-Up', 'milestones': [{'type': 'STARTED', 'achievements': [{'comment': "14 completers of phase I didn't split up evenly (same way as phase I) in the riluzole/placebo phase.", 'groupId': 'FG000', 'numSubjects': '6'}, {'comment': "14 completers of phase I didn't split up evenly (same way as phase I) in the riluzole/placebo phase.", 'groupId': 'FG001', 'numSubjects': '8'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '5'}, {'groupId': 'FG001', 'numSubjects': '8'}]}, {'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': 'The intent-to-treat sample (n=26) was recruited from media/internet advertising (14), psychiatrist referral (8), or self-referral from the New York Mood Disorders Support Group (4). Patients had marked depressive severity, chronicity, and anxiety comorbidity, and were highly pharmacotherapy-resistant.', 'preAssignmentDetails': '2-wk psychotropic medication washout period (4 wk for fluoxetine)'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'BG000'}, {'value': '13', 'groupId': 'BG001'}, {'value': '26', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Lamotrigine Pre-Treatment', 'description': 'Patients who met enrolment criteria for phase 1 were randomly allocated to lamotrigine or placebo by a permuted block procedure consisting of blocks of two or four patients. The randomization list was created by a biostatistician with no patient contact. Following baseline ratings, 2 h prior to i.v. ketamine infusion, patients received 300 mg lamotrigine or placebo by mouth.'}, {'id': 'BG001', 'title': 'Placebo Pre-Treatment', 'description': 'Patients who met enrolment criteria for phase 1 were randomly allocated to lamotrigine or placebo by a permuted block procedure consisting of blocks of two or four patients. The randomization list was created by a biostatistician with no patient contact. Following baseline ratings, 2 h prior to i.v. ketamine infusion, patients received 300 mg lamotrigine or placebo by mouth.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '48.2', 'spread': '11.8', 'groupId': 'BG000'}, {'value': '48.2', 'spread': '11.8', 'groupId': 'BG001'}, {'value': '48.2', 'spread': '11.8', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '5', 'groupId': 'BG001'}, {'value': '10', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '8', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '16', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '13', 'groupId': 'BG000'}, {'value': '13', 'groupId': 'BG001'}, {'value': '26', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'FACTORIAL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 26}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2006-12'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-07', 'completionDateStruct': {'date': '2008-09', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2019-07-16', 'studyFirstSubmitDate': '2007-01-04', 'resultsFirstSubmitDate': '2013-09-05', 'studyFirstSubmitQcDate': '2007-01-04', 'lastUpdatePostDateStruct': {'date': '2019-07-31', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2016-02-19', 'studyFirstPostDateStruct': {'date': '2007-01-05', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2016-03-21', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2008-07', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Efficacy of Lamotrigine in Decreasing IV Ketamine Psychotomimetic Side Effects', 'timeFrame': '24, 48, or 72-hrs', 'description': 'Response rate and side effect differences to IV ketamine infusion based on lamotrigine and placebo pretreatment groups'}], 'primaryOutcomes': [{'measure': 'Montgomery-Asberg Depression Rating Scale (MARDS) Score (Acute Response to IV Ketamine in Patients With Treatment Resistant Major Depression)', 'timeFrame': '24 Hours', 'description': 'Montgomery-Asberg Depression Rating Scale, each of the ten items can be scored from 0 (absence of symptoms to 6 most severe) and has a total score range of 0-60. A lower score on a MADRS indicates a less severe depression. The primary outcome for the initial phase of the trial was the 24-h MADRS score, which included all 10 MADRS items.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'conditions': ['Major Depression']}, 'referencesModule': {'references': [{'pmid': '25271445', 'type': 'DERIVED', 'citation': 'Wan LB, Levitch CF, Perez AM, Brallier JW, Iosifescu DV, Chang LC, Foulkes A, Mathew SJ, Charney DS, Murrough JW. Ketamine safety and tolerability in clinical trials for treatment-resistant depression. J Clin Psychiatry. 2015 Mar;76(3):247-52. doi: 10.4088/JCP.13m08852.'}, {'pmid': '19545857', 'type': 'DERIVED', 'citation': 'Price RB, Nock MK, Charney DS, Mathew SJ. Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression. Biol Psychiatry. 2009 Sep 1;66(5):522-6. doi: 10.1016/j.biopsych.2009.04.029. Epub 2009 Jul 9.'}, {'pmid': '19288975', 'type': 'DERIVED', 'citation': 'Mathew SJ, Murrough JW, aan het Rot M, Collins KA, Reich DL, Charney DS. Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression: a pilot randomized, placebo-controlled continuation trial. Int J Neuropsychopharmacol. 2010 Feb;13(1):71-82. doi: 10.1017/S1461145709000169. Epub 2009 Mar 17.'}]}, 'descriptionModule': {'briefSummary': 'This study is examining the safety and effectiveness of two medications, ketamine and riluzole, in treating patients with treatment resistant major depressive disorder. This study will also examine the effectiveness of an FDA approved drug called lamotrigine in decreasing the potential side effects associated with ketamine.', 'detailedDescription': 'This research proposal will investigate a glutamate-modulating agent, riluzole, in treatment-resistant patients who exhibit an acute, sustained response to a single dose of intravenous (IV) racemic ketamine. Fifty ketamine-responders will be randomized to riluzole or placebo in a 4-week, randomized, double-blind, continuation-phase study.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '21 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n1. Male or female patients, 21- 70 years of age\n2. Subjects have a history of at least one previous episode of depression prior to the current episode (recurrent major depressive disorder) or have chronic major depressive disorder (at least two years' duration)\n3. Subjects have not responded to an adequate trial of one antidepressant in the current episode\n\nExclusion Criteria:\n\n1. Female subjects who are either pregnant or nursing\n2. Serious, unstable illnesses\n3. Any previous use or treatment with ketamine, or riluzole\n4. Past intolerance to lamotrigine, including drug rash"}, 'identificationModule': {'nctId': 'NCT00419003', 'briefTitle': 'Research Study for Major Depressive Disorder: Investigation of Glutamate Medications', 'organization': {'class': 'OTHER', 'fullName': 'Baylor College of Medicine'}, 'officialTitle': 'Continuation Riluzole in the Prevention of Relapse Following Ketamine in Major Depression', 'orgStudyIdInfo': {'id': '05-0850'}, 'secondaryIdInfos': [{'id': '5M01RR000071-46', 'link': 'https://reporter.nih.gov/quickSearch/5M01RR000071-46', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Lamotrigine Pre-Treatment', 'description': 'Patients who met enrolment criteria for phase 1 were randomly allocated to lamotrigine or placebo by a permuted block procedure consisting of blocks of two or four patients. The randomization list was created by a biostatistician with no patient contact. 300 mg of lamotrigine 2 hrs prior to ketamine infusion. Responders were randomized to one of two continuation pharmacotherapy groups, receiving either two capsules of riluzole 50 mg each (100 mg/d) or matching pill placebo under double-blind conditions.', 'interventionNames': ['Drug: Lamotrigine', 'Drug: Ketamine', 'Drug: Riluzole']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo Pre-Treatment', 'description': '2 hours prior to ketamine infusion each patient received three capsules of placebo identical in size, weight, appearance, and taste to the lamotrigine tablets. Responders were randomized to one of two continuation pharmacotherapy groups, receiving either two capsules of riluzole 50 mg each (100 mg/d) or matching pill placebo under double-blind conditions.', 'interventionNames': ['Drug: Ketamine', 'Drug: Riluzole']}], 'interventions': [{'name': 'Lamotrigine', 'type': 'DRUG', 'otherNames': ['lamictal'], 'description': 'anticonvulsant medication', 'armGroupLabels': ['Lamotrigine Pre-Treatment']}, {'name': 'Ketamine', 'type': 'DRUG', 'otherNames': ['ketalar'], 'description': 'subanesthetic dose of NMDAR antagonist', 'armGroupLabels': ['Lamotrigine Pre-Treatment', 'Placebo Pre-Treatment']}, {'name': 'Riluzole', 'type': 'DRUG', 'otherNames': ['rilutek'], 'description': 'glutamate release inhibitor', 'armGroupLabels': ['Lamotrigine Pre-Treatment', 'Placebo Pre-Treatment']}]}, 'contactsLocationsModule': {'locations': [{'zip': '10029', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'Mount Sinai School of Medicine', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}], 'overallOfficials': [{'name': 'Sanjay Mathew, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Baylor College of Medicine'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Baylor College of Medicine', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Alliance for Research on Schizophrenia and Depression', 'class': 'OTHER'}, {'name': 'National Center for Research Resources (NCRR)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'MD', 'investigatorFullName': 'Sanjay Johan Mathew', 'investigatorAffiliation': 'Baylor College of Medicine'}}}}