Ignite Creation Date:
2025-12-24 @ 11:56 PM
Ignite Modification Date:
2026-02-22 @ 3:56 PM
Study NCT ID:
NCT02134951
Status:
COMPLETED
Last Update Posted:
2018-08-17
First Post:
2014-05-07
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Biomarker Assessment of Glutamatergic Target Engagement
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D007649', 'term': 'Ketamine'}, {'id': 'D000077330', 'term': 'Saline Solution'}, {'id': 'D012965', 'term': 'Sodium Chloride'}], 'ancestors': [{'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': 'D000077324', 'term': 'Crystalloid Solutions'}, {'id': 'D007552', 'term': 'Isotonic Solutions'}, {'id': 'D012996', 'term': 'Solutions'}, {'id': 'D004364', 'term': 'Pharmaceutical Preparations'}, {'id': 'D002712', 'term': 'Chlorides'}, {'id': 'D006851', 'term': 'Hydrochloric Acid'}, {'id': 'D017606', 'term': 'Chlorine Compounds'}, {'id': 'D007287', 'term': 'Inorganic Chemicals'}, {'id': 'D017670', 'term': 'Sodium Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'mc157@columbia.edu', 'phone': '646-774-8436', 'title': 'Marlene Carlson', 'organization': 'New York State Psychiatric Institute'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'Ketamine', 'otherNumAtRisk': 39, 'deathsNumAtRisk': 39, 'otherNumAffected': 6, 'seriousNumAtRisk': 39, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Placebo', 'otherNumAtRisk': 20, 'deathsNumAtRisk': 20, 'otherNumAffected': 0, 'seriousNumAtRisk': 20, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'ketamine psychological effect', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numEvents': 6, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 20, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Glutamate + Glutamine (Glx) Response', 'denoms': [{'units': 'Participants', 'counts': [{'value': '31', 'groupId': 'OG000'}, {'value': '16', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ketamine', 'description': 'IV infusion of ketamine 0.23mg/kg bolus over 1 minutes followed by 0.58 mg/kg/hr over 30 minutes then 0.29mg/kg/hr over 64 minutes\n\nKetamine: intravenous infusion of saline solution with ketamine'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Placebo group will receive normal saline\n\nNormal saline: Normal saline will be used for placebo in this group'}], 'classes': [{'categories': [{'measurements': [{'value': '0.015', 'spread': '.002', 'groupId': 'OG000'}, {'value': '0.007', 'spread': '.003', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Day 1', 'description': 'Compare changes in Glx response to infusion of ketamine vs placebo, as measured by proton magnetic resonance spectroscopy (¹H MRS). Calculated by post-pre changes in the Glx over creatinine ratios, with higher values indicating higher Glx/creatinine ratios.', 'unitOfMeasure': 'Glx over creatinine ratio', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Glx response in 1st 15 minutes post ketamine'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Pharmacological Blood-oxygen-level Dependent (pharmacoBOLD) Response', 'denoms': [{'units': 'Participants', 'counts': [{'value': '34', 'groupId': 'OG000'}, {'value': '19', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ketamine', 'description': 'IV infusion of ketamine 0.23mg/kg bolus over 1 minutes followed by 0.58 mg/kg/hr over 30 minutes then 0.29mg/kg/hr over 64 minutes\n\nKetamine: intravenous infusion of saline solution with ketamine'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Placebo group will receive normal saline\n\nNormal saline: Normal saline will be used for placebo in this group'}], 'classes': [{'categories': [{'measurements': [{'value': '.91', 'spread': '.1', 'groupId': 'OG000'}, {'value': '-0.27', 'spread': '0.14', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Day 14', 'description': 'Compare changes inpharmacoBOLD in response to infusion of ketamine vs. placebo, as measured by resting state functional magnetic resonance imaging. Calculated by post-pre changes, with higher values indicating higher response', 'unitOfMeasure': 'BOLD signal units', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Ketamine', 'description': 'IV infusion of ketamine 0.23mg/kg bolus over 1 minutes followed by 0.58 mg/kg/hr over 30 minutes then 0.29mg/kg/hr over 64 minutes\n\nKetamine: intravenous infusion of saline solution with ketamine'}, {'id': 'FG001', 'title': 'Placebo', 'description': 'Placebo group will receive normal saline\n\nNormal saline: Normal saline will be used for placebo in this group'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '39'}, {'groupId': 'FG001', 'numSubjects': '20'}]}, {'type': 'COMPLETED', 'achievements': [{'comment': 'number of subjects with at least one valid scan', 'groupId': 'FG000', 'numSubjects': '39'}, {'comment': 'number of subjects with at least one valid scan', 'groupId': 'FG001', 'numSubjects': '20'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'preAssignmentDetails': '65 subjects were randomized, with results (Number started) reported for the 59 subjects randomized subjects with at least one valid scan'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '39', 'groupId': 'BG000'}, {'value': '20', 'groupId': 'BG001'}, {'value': '59', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Ketamine', 'description': 'randomized to ketamine'}, {'id': 'BG001', 'title': 'Placebo', 'description': 'randomized to placebo'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '31.1', 'spread': '9.6', 'groupId': 'BG000'}, {'value': '32.2', 'spread': '10.2', 'groupId': 'BG001'}, {'value': '31.5', 'spread': '9.8', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '21', 'groupId': 'BG000'}, {'value': '16', 'groupId': 'BG001'}, {'value': '37', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '18', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '22', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 65}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2014-05'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-08', 'completionDateStruct': {'date': '2015-11', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2018-08-15', 'studyFirstSubmitDate': '2014-05-07', 'resultsFirstSubmitDate': '2017-06-08', 'studyFirstSubmitQcDate': '2014-05-07', 'lastUpdatePostDateStruct': {'date': '2018-08-17', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2018-02-12', 'studyFirstPostDateStruct': {'date': '2014-05-09', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2018-02-13', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2015-10', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Pharmacological Blood-oxygen-level Dependent (pharmacoBOLD) Response', 'timeFrame': 'Day 14', 'description': 'Compare changes inpharmacoBOLD in response to infusion of ketamine vs. placebo, as measured by resting state functional magnetic resonance imaging. Calculated by post-pre changes, with higher values indicating higher response'}], 'primaryOutcomes': [{'measure': 'Glutamate + Glutamine (Glx) Response', 'timeFrame': 'Day 1', 'description': 'Compare changes in Glx response to infusion of ketamine vs placebo, as measured by proton magnetic resonance spectroscopy (¹H MRS). Calculated by post-pre changes in the Glx over creatinine ratios, with higher values indicating higher Glx/creatinine ratios.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'conditions': ['Healthy Controls']}, 'referencesModule': {'references': [{'pmid': '29167877', 'type': 'DERIVED', 'citation': 'Javitt DC, Carter CS, Krystal JH, Kantrowitz JT, Girgis RR, Kegeles LS, Ragland JD, Maddock RJ, Lesh TA, Tanase C, Corlett PR, Rothman DL, Mason G, Qiu M, Robinson J, Potter WZ, Carlson M, Wall MM, Choo TH, Grinband J, Lieberman JA. Utility of Imaging-Based Biomarkers for Glutamate-Targeted Drug Development in Psychotic Disorders: A Randomized Clinical Trial. JAMA Psychiatry. 2018 Jan 1;75(1):11-19. doi: 10.1001/jamapsychiatry.2017.3572.'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to assess the relative feasibility of 2 potential functional measures of target engagement (Glx MRS, BOLD fMRI) to systematically assess mGluR 2/3 in drug development for psychotic spectrum disorders.', 'detailedDescription': 'This is a pilot study of healthy subject to assess the feasibility of Glx MRS and BOLD fMRI to measure ketamine induced changes in glutamatergic indices. The investigators will randomize 18 subjects at each site. Subjects will be randomized to ketamine or placebo in a 2:1 ratio and receive two drug challenges separated by at least two weeks. Ketamine challenge is used to induce a "glutamate surge" within prefrontal brain regions that can be detected using neurochemical and functional imaging techniques. Each subject will receive MRS and BOLD fMRI during each challenge day. The goal of the pilot study is to assess the feasibility of both the proposed ketamine challenge paradigm and of the proposed imaging-based biomarkers. Specific indices to be used in assessing feasibility will include effect size, cross-site and cross-subject reliability, safety, and subject tolerability as similar studies will be performed independently at Yale and UC Davis. Second this information will be used to select and refine final study parameters for a subsequent full proof-of-clinical mechanism (POCM) study investigating the effect of Pomaglumetad on ketamine-induced MRS and fMRI effects.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '55 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age 18-55\n* Negative Urine Toxicology\n* No present or past psychiatric conditions (including substance abuse or dependence, with the exception of nicotine dependence)\n* No family history of schizophrenia in a first-degree relative\n\nExclusion Criteria:\n\n* Any current DSM IV Axis I disorder and/or past substance abuse of dependence (nicotine dependence is allowed)\n* Any current use of amphetamines, opiates, cocaine, sedative-hypnotics, or cannabis\n* Current (i.e., within the last 3 months) treatment with any psychotropic medications\n* Pregnancy, lactation, or lack of use of effective birth control\n* Presence of positive history of significant medical or neurological illness (including any history of seizure), including high blood pressure (SBP \\>140, DBP \\>90), low blood pressure (SBP \\<100, DBP \\<60), orthostatic BP change\\>20% (1/3 SBP + 2/3 DBP) or cardiac illness or resting heart rate \\>100 or \\<50\n* History of significant violent behavior\n* History of recreational ketamine use, recreational PCP use, or an adverse reaction to ketamine. Subjects who have participated prior research ketamine studies will be eligible providing they have participated in no more than 5 previous research ketamine infusions. Subjects can have infusions not more frequently than biweekly and not more than 1/month on average, therefore subjects entering the study will need to wait 1 month if they had a single infusion and 6 weeks if they have had two closely spaced infusions.\n* Contraindication to MRI scanning, including metal implants or claustrophobia. Metal implants, pacemaker, other metal (e.g. shrapnel or surgical prostheses) or paramagnetic objects contained within the body which may present a risk to the subject or interfere with the MR scan, as determined in consultation with a neuroradiologist and according to the guidelines set forth in the following reference book commonly used by neuroradiologists: "Guide to MR procedures and metallic objects", F.G. Shellock, Lippincott Williams and Wilkins NY 2001\n* Color Blindness'}, 'identificationModule': {'nctId': 'NCT02134951', 'briefTitle': 'Biomarker Assessment of Glutamatergic Target Engagement', 'organization': {'class': 'OTHER', 'fullName': 'New York State Psychiatric Institute'}, 'officialTitle': 'Biomarker Assessment of Glutamatergic Target Engagement', 'orgStudyIdInfo': {'id': '6925'}, 'secondaryIdInfos': [{'id': 'HHS-N-271-2012-0000-7-I', 'type': 'OTHER', 'domain': 'NIH/NIMH contract number'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'ketamine', 'description': 'IV infusion of ketamine 0.23mg/kg bolus over 1 minutes followed by 0.58 mg/kg/hr over 30 minutes then 0.29mg/kg/hr over 64 minutes', 'interventionNames': ['Drug: Ketamine']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Placebo group will receive normal saline', 'interventionNames': ['Drug: Normal saline']}], 'interventions': [{'name': 'Ketamine', 'type': 'DRUG', 'otherNames': ['ketamine hydrochloride'], 'description': 'intravenous infusion of saline solution with ketamine', 'armGroupLabels': ['ketamine']}, {'name': 'Normal saline', 'type': 'DRUG', 'otherNames': ['saline'], 'description': 'Normal saline will be used for placebo in this group', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '95817', 'city': 'Sacramento', 'state': 'California', 'country': 'United States', 'facility': 'University of California Davis', 'geoPoint': {'lat': 38.58157, 'lon': -121.4944}}, {'zip': '06511', 'city': 'New Haven', 'state': 'Connecticut', 'country': 'United States', 'facility': 'Yale University', 'geoPoint': {'lat': 41.30815, 'lon': -72.92816}}, {'zip': '10032', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'New York State Psychiatric Institute', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}], 'overallOfficials': [{'name': 'Jeffrey A Lieberman, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'New York State Psychiatric Institute'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'New York State Psychiatric Institute', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Institute of Mental Health (NIMH)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Manager', 'investigatorFullName': 'Marlene Carlson', 'investigatorAffiliation': 'New York State Psychiatric Institute'}}}}