Ignite Creation Date:
2025-12-24 @ 6:38 PM
Ignite Modification Date:
2026-04-11 @ 5:37 AM
Study NCT ID:
NCT01880957
Status:
COMPLETED
Last Update Posted:
2022-07-20
First Post:
2013-06-17
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
PET and MRI Brain Imaging of Bipolar Disorder
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001714', 'term': 'Bipolar Disorder'}, {'id': 'D003866', 'term': 'Depressive Disorder'}], 'ancestors': [{'id': 'D000068105', 'term': 'Bipolar and Related Disorders'}, {'id': 'D019964', 'term': 'Mood Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D008094', 'term': 'Lithium'}, {'id': 'D016651', 'term': 'Lithium Carbonate'}, {'id': 'D000077213', 'term': 'Lamotrigine'}], 'ancestors': [{'id': 'D008672', 'term': 'Metals, Alkali'}, {'id': 'D004602', 'term': 'Elements'}, {'id': 'D007287', 'term': 'Inorganic Chemicals'}, {'id': 'D019565', 'term': 'Metals, Light'}, {'id': 'D008670', 'term': 'Metals'}, {'id': 'D002254', 'term': 'Carbonates'}, {'id': 'D000468', 'term': 'Alkalies'}, {'id': 'D002255', 'term': 'Carbonic Acid'}, {'id': 'D017554', 'term': 'Carbon Compounds, Inorganic'}, {'id': 'D018020', 'term': 'Lithium Compounds'}, {'id': 'D014227', 'term': 'Triazines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'Christine.Delorenzo@stonybrookmedicine.edu', 'phone': '(631) 638-1523', 'title': 'Dr. Christine DeLorenzo', 'organization': 'Stony Brook University'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': 'Limitations include: 1. a small sample size, which precludes investigation into interaction factors (e.g. sex/BPD subtype); 2. a short washout duration (3 weeks for ethical reasons), which may not be sufficient to abate treatment effects; 3. scans for both patients and controls conducted across multiple sites, though, importantly, all pre- and post-treatment scans within-participant were conducted at the same site.'}}, 'adverseEventsModule': {'timeFrame': 'Full study duration for participants: enrollment through final data collection (approximately 6 months)', 'description': 'Definitions for adverse event and/or serious adverse event used to collect adverse event information matches clinicaltrials.gov.', 'eventGroups': [{'id': 'EG000', 'title': 'Patients With Depression', 'description': 'Bipolar patients with this condition will receive lithium administered as follows: Day 1, 2 and 3, 300 mg bid; Days 4-7 lithium 300 qam and 600 qhs. Lithium level will be checked as close to Day 7 as possible and titrated to a therapeutic plasma level of 0.8-1.2 mEq/l. Subjects will not undergo lithium monotherapy if they have a documented history of at least two failed trials of lithium of at least 4 weeks duration with therapeutic blood levels for a major depressive episode\n\nLithium', 'otherNumAtRisk': 47, 'deathsNumAtRisk': 47, 'otherNumAffected': 0, 'seriousNumAtRisk': 47, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Healthy Volunteers', 'description': 'Participants in this group underwent baseline assessment for Hamilton Depression Rating Scale and Baseline PET and MRI Imaging. No treatment was provided for this group.', 'otherNumAtRisk': 29, 'deathsNumAtRisk': 29, 'otherNumAffected': 0, 'seriousNumAtRisk': 29, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Post-Lithium Treatment Hamilton Depression Rating Scale (HDRS)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '19', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Patients With BPD', 'description': 'Participants in this group included patients with bipolar depression who were subsequently treated with Lithium. Following baseline PET and MRI scans, treatment was initiated with lithium monotherapy. In brief: days 1-3: 300mg 2x/day, days 4-7: 300mg every morning and 600mg every night; titration to a therapeutic plasma level of 0.8-1.2 mEq/l. Following eight weeks of treatment, patients were rescanned with PET and MRI and reassessed with the HDRS-24.'}], 'classes': [{'categories': [{'measurements': [{'value': '-44.49', 'spread': '34.17', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '8 weeks', 'description': 'Patients will have a Hamilton Depression Rating Scale-24 (HDRS) score obtained at baseline. Minimum score 0, maximum possible score 75; the higher the score on the scale, the more severe the degree of depression. Participants must have an HDRS score of at least 15 to be eligible. After eight weeks of medication treatment, the HDRS score will be reevaluated with the HDRS-24 (and rescanned with PET and MRI). Participants who have a 50% or greater decrease in their HDRS-24 score will be considered responders (to Lithium treatment).', 'unitOfMeasure': 'Percent Change in HDRS-24 Score', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Pre-to-Post lithium treatment change in HDRS Score'}, {'type': 'PRIMARY', 'title': 'Prediction of Treatment Response', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14', 'groupId': 'OG000'}, {'value': '14', 'groupId': 'OG001'}, {'value': '14', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Prediction by Pre-treatment 5-HTT', 'description': 'Data analysis to determine whether pre-treatment 5-HTT binding potential along with pre-treatment HDRS-24 predicted treatment response (remission status).'}, {'id': 'OG001', 'title': 'Prediction by Pre-treatment 5-HT1A', 'description': 'Data analysis to determine whether pre-treatment 5-HT1A binding potential along with pre-treatment HDRS-24 predicted treatment response (remission status).'}, {'id': 'OG002', 'title': 'Combinatorial Prediction Using Pre-Treatment 5-HTT & 5-HT1A', 'description': 'Data analysis to determine whether pre-treatment 5-HTT \\& 5-HT1A binding potential along with pre-treatment HDRS-24 predicted treatment response (remission status).'}], 'classes': [{'title': 'Prediction Accuracy = True positive + negative divided by the sum of true + false positive/negative', 'categories': [{'measurements': [{'value': '71.4', 'groupId': 'OG000'}, {'value': '85.7', 'groupId': 'OG001'}, {'value': '84.6', 'groupId': 'OG002'}]}]}, {'title': 'Prediction Specificity = True negatives divided by the sum of true negative and false positive', 'categories': [{'measurements': [{'value': '77.8', 'groupId': 'OG000'}, {'value': '87.5', 'groupId': 'OG001'}, {'value': '87.5', 'groupId': 'OG002'}]}]}, {'title': 'Prediction Sensitivity= True positives divided by the sum of true positive and false negative', 'categories': [{'measurements': [{'value': '60', 'groupId': 'OG000'}, {'value': '80', 'groupId': 'OG001'}, {'value': '60', 'groupId': 'OG002'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '8 Weeks', 'description': 'Outcome measures were generated following LASSO linear regression analysis using pretreament HDRS-24 AND..\n\n1. pre-treatment 5-HTT OR\n2. pretreatment 5-HT1A OR\n3. the combination of both 5-HTT and 5-HT1A binding potential\n\n * to predict post-treatment response defined by a dichotomous remission status variable (remitter vs. non-remitter, where remitter is defined a priori by HDRS-24 \\<10 post-treatment and a reduction of greater than or equal to 50% in HDRS-24 pre-to-post treatment). Outcome measure is reported as percent accuracy, sensitivity, or specificity in predicting remitter status outcomes.', 'unitOfMeasure': 'Percentage', 'reportingStatus': 'POSTED', 'populationDescription': 'Remission status prediction by groups: accuracy, specificity, and sensitivity. The analyzed population here must have completed both pre- and post-treatment scans for BOTH 5-HTT and 5-HT1A and have 8 weeks of HDRS-24 followup so the predictive power of each individual tracer could be assessed as well as the combination of the two tracers. This is a smaller population that each tracer individually or the outcome of the HDRS-24 scale alone.'}, {'type': 'SECONDARY', 'title': 'Group Differences in 5-HTT Binding Potential', 'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'OG000'}, {'value': '19', 'groupId': 'OG001'}, {'value': '14', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Healthy Volunteers', 'description': 'Control participants for baseline measures'}, {'id': 'OG001', 'title': 'Pre-treatment 5-HTT Binding Potential (Baseline)', 'description': 'Participants that presented with Bipolar depression upon enrollment into the study'}, {'id': 'OG002', 'title': 'Post-treatment 5-HTT Binding Potential (8 Weeks)', 'description': 'Participants that presented with Bipolar depression and were treated with Lithium for 8 weeks.'}], 'classes': [{'title': 'Grey Matter of Cerebellum', 'categories': [{'measurements': [{'value': '93.27', 'spread': '17.86', 'groupId': 'OG000'}, {'value': '88', 'spread': '1.87', 'groupId': 'OG001'}, {'value': '88.70', 'spread': '21.71', 'groupId': 'OG002'}]}]}, {'title': 'Midbrain', 'categories': [{'measurements': [{'value': '264.82', 'spread': '32.47', 'groupId': 'OG000'}, {'value': '81.73', 'spread': '18.59', 'groupId': 'OG001'}, {'value': '181.13', 'spread': '90.20', 'groupId': 'OG002'}]}]}, {'title': 'Anterior Cingulate', 'categories': [{'measurements': [{'value': '131.80', 'spread': '26.99', 'groupId': 'OG000'}, {'value': '187.48', 'spread': '60.73', 'groupId': 'OG001'}, {'value': '130.04', 'spread': '30.73', 'groupId': 'OG002'}]}]}, {'title': 'Amygdala', 'categories': [{'measurements': [{'value': '198.56', 'spread': '27.64', 'groupId': 'OG000'}, {'value': '116.94', 'spread': '28.73', 'groupId': 'OG001'}, {'value': '166.73', 'spread': '61.75', 'groupId': 'OG002'}]}]}], 'paramType': 'MEAN', 'timeFrame': '8 Weeks', 'description': 'Differences in mean of 5-HTT binding potential between patients with depression pre-treatment, post-treatment, compared to healthy volunteers. Broadly, binding potential is defined as the ratio of the tracer concentration in tissue to the free plasma concentration. It is a measure of the density of "available" targets (e.g. 5-HTT) \\& the affinity of the ligand (tracer) to that target.', 'unitOfMeasure': 'Weighted Mean Binding Potential', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Comparison of mean binding potential across patients pre-treatment, post-treatment, and controls.'}, {'type': 'SECONDARY', 'title': 'Group Differences in 5-HT1A Binding Potential', 'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'OG000'}, {'value': '17', 'groupId': 'OG001'}, {'value': '13', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Healthy Volunteers', 'description': 'Control participants for baseline measures'}, {'id': 'OG001', 'title': 'Pre-treatment 5-HT1A Binding Potential (Baseline)', 'description': 'Participants that presented with Bipolar depression upon enrollment into the study'}, {'id': 'OG002', 'title': 'Post-treatment 5-HT1A Binding Potential (8 Weeks)', 'description': 'Participants that presented with Bipolar depression and were treated with Lithium for 8 weeks.'}], 'classes': [{'title': 'Raphe Nucleus', 'categories': [{'measurements': [{'value': '8.91', 'spread': '3.15', 'groupId': 'OG000'}, {'value': '9.62', 'spread': '1.79', 'groupId': 'OG001'}, {'value': '8.57', 'spread': '2.58', 'groupId': 'OG002'}]}]}, {'title': 'Parahippocampal Gyrus', 'categories': [{'measurements': [{'value': '12.48', 'spread': '2.41', 'groupId': 'OG000'}, {'value': '14.88', 'spread': '3.13', 'groupId': 'OG001'}, {'value': '15.79', 'spread': '3.75', 'groupId': 'OG002'}]}]}, {'title': 'Amygdala', 'categories': [{'measurements': [{'value': '20.8', 'spread': '5.26', 'groupId': 'OG000'}, {'value': '17.86', 'spread': '4.39', 'groupId': 'OG001'}, {'value': '14.01', 'spread': '3.41', 'groupId': 'OG002'}]}]}, {'title': 'Hippocampus', 'categories': [{'measurements': [{'value': '27.06', 'spread': '8.40', 'groupId': 'OG000'}, {'value': '30.17', 'spread': '7.84', 'groupId': 'OG001'}, {'value': '28.39', 'spread': '7.73', 'groupId': 'OG002'}]}]}], 'paramType': 'MEAN', 'timeFrame': '8 Weeks', 'description': 'Differences in mean of 5-HT1A binding potential between patients with depression pre-treatment, post-treatment, compared to healthy volunteers. Broadly, binding potential is defined as the ratio of the tracer concentration in tissue to the free plasma concentration. It is a measure of the density of "available" targets (e.g. 5-HT1A) \\& the affinity of the ligand (tracer) to that target.', 'unitOfMeasure': 'Weighted Mean Binding Potential', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Comparison of mean binding potential across patients pre-treatment, post-treatment, and controls.'}, {'type': 'SECONDARY', 'title': 'Relationship Between Change in 5-HTT or 5-HT1A Binding Potential Pre- to Post Treatment and Lithium Treatment Response', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14', 'groupId': 'OG000'}, {'value': '13', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Change in 5-HTT Binding Potential vs. Treatment Response', 'description': 'Data analysis to determine whether there is relationship between the change in 5-HTT binding potential and treatment response.'}, {'id': 'OG001', 'title': 'Change in 5-HT1A Binding Potential and Treatment Response', 'description': 'Data analysis to determine whether there is relationship between the change in 5-HTT binding potential and treatment response.'}], 'classes': [{'title': 'R-Squared: 5-HTT Midbrain', 'categories': [{'measurements': [{'value': '0.061', 'groupId': 'OG000'}, {'value': 'NA', 'comment': 'Region not analyzed for this tracer due to lack of target.', 'groupId': 'OG001'}]}]}, {'title': 'R-Squared: 5-HT1A Raphe', 'categories': [{'measurements': [{'value': 'NA', 'comment': 'Region not analyzed for this tracer due to lack of target.', 'groupId': 'OG000'}, {'value': '0.086', 'groupId': 'OG001'}]}]}, {'title': 'R-Squared: 5-HT1A Hippocampus', 'categories': [{'measurements': [{'value': 'NA', 'comment': 'Region not analyzed for this tracer due to lack of target.', 'groupId': 'OG000'}, {'value': '0.073', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '8 weeks', 'description': 'Linear regression \\& correlation to assess the relationship between between change in binding potential pre- to post treatment vs. treatment response', 'unitOfMeasure': 'Percent Change in Binding Potential', 'reportingStatus': 'POSTED', 'populationDescription': 'Linear regression between change in PET binding potential pre and post treatment and treatment response.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Patients With Depression', 'description': 'Patients in this condition will receive lithium administered as follows: Day 1, 2 and 3, 300 mg bid; Days 4-7 lithium 300 qam and 600 qhs. Lithium level will be checked as close to Day 7 as possible and titrated to a therapeutic plasma level of 0.8-1.2 mEq/l. Subjects will not undergo lithium monotherapy if they have a documented history of at least two failed trials of lithium of at least 4 weeks duration with therapeutic blood levels for a major depressive episode\n\nLithium'}, {'id': 'FG001', 'title': 'Healthy Volunteers', 'description': 'Participants in this group underwent baseline assessment for Hamilton Depression Rating Scale and Baseline PET and MRI Imaging. No treatment was provided for this group.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '47'}, {'groupId': 'FG001', 'numSubjects': '29'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '19'}, {'groupId': 'FG001', 'numSubjects': '29'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '28'}, {'groupId': 'FG001', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Diagnosis: Unipolar Depression', 'reasons': [{'groupId': 'FG000', 'numSubjects': '12'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '11'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Poor Tolerance to Lithium/Declined Treatment', 'reasons': [{'groupId': 'FG000', 'numSubjects': '5'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Dates of Recruitment: 11/2011 - 05/2017 Location: University Medical Centers (Columbia, Stony Brook University)', 'preAssignmentDetails': '1. Inclusion/Exclusion Criteria must be met prior to beginning study protocols.\n2. Wash-out Period: For participants in the patient group, all were required to be 3 weeks medication free before beginning the study.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '31', 'groupId': 'BG000'}, {'value': '23', 'groupId': 'BG001'}, {'value': '54', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Patients With Depression', 'description': 'Patients with Bipolar depression will receive lithium administered as follows: Day 1, 2 and 3, 300 mg bid; Days 4-7 lithium 300 qam and 600 qhs. Lithium level will be checked as close to Day 7 as possible and titrated to a therapeutic plasma level of 0.8-1.2 mEq/l. Subjects will not undergo lithium monotherapy if they have a documented history of at least two failed trials of lithium of at least 4 weeks duration with therapeutic blood levels for a major depressive episode\n\nLithium'}, {'id': 'BG001', 'title': 'Healthy Volunteers', 'description': 'Participants in this group underwent baseline assessment for Hamilton Depression Rating Scale and Baseline PET and MRI Imaging. No treatment was provided for this group.'}, {'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': '31', 'groupId': 'BG000'}, {'value': '23', 'groupId': 'BG001'}, {'value': '54', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '15', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '27', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '16', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '27', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '7', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '23', 'groupId': 'BG000'}, {'value': '16', 'groupId': 'BG001'}, {'value': '39', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '6', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Hamilton Depression Rating Sale', 'classes': [{'categories': [{'measurements': [{'value': '26.19', 'spread': '5.86', 'groupId': 'BG000'}, {'value': '1.62', 'spread': '2.10', 'groupId': 'BG001'}, {'value': '16.71', 'spread': '13.27', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'Patients will have a Hamilton Depression Rating Scale-24 (HDRS) score obtained at baseline. Minimum score 0, maximum possible score 75; the higher the score on the scale, the more severe the degree of depression. Participants must have an HDRS score of at least 15 to be eligible.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION'}], 'populationDescription': 'The number of participants reflected in each group are those that were available for both PET and HDRS-24 baseline measures that also met quality control standards for the imaging data. This number differs slightly from total participants enrolled.'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2019-12-13', 'size': 982168, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2022-03-21T21:14', 'hasProtocol': True}, {'date': '2017-12-14', 'size': 248933, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2022-03-22T23:31', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 76}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2011-11-08', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-07', 'completionDateStruct': {'date': '2017-06-23', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2022-07-11', 'studyFirstSubmitDate': '2013-06-17', 'resultsFirstSubmitDate': '2022-03-23', 'studyFirstSubmitQcDate': '2013-06-18', 'lastUpdatePostDateStruct': {'date': '2022-07-20', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2022-06-03', 'studyFirstPostDateStruct': {'date': '2013-06-19', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2022-06-29', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2017-06-23', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Post-Lithium Treatment Hamilton Depression Rating Scale (HDRS)', 'timeFrame': '8 weeks', 'description': 'Patients will have a Hamilton Depression Rating Scale-24 (HDRS) score obtained at baseline. Minimum score 0, maximum possible score 75; the higher the score on the scale, the more severe the degree of depression. Participants must have an HDRS score of at least 15 to be eligible. After eight weeks of medication treatment, the HDRS score will be reevaluated with the HDRS-24 (and rescanned with PET and MRI). Participants who have a 50% or greater decrease in their HDRS-24 score will be considered responders (to Lithium treatment).'}, {'measure': 'Prediction of Treatment Response', 'timeFrame': '8 Weeks', 'description': 'Outcome measures were generated following LASSO linear regression analysis using pretreament HDRS-24 AND..\n\n1. pre-treatment 5-HTT OR\n2. pretreatment 5-HT1A OR\n3. the combination of both 5-HTT and 5-HT1A binding potential\n\n * to predict post-treatment response defined by a dichotomous remission status variable (remitter vs. non-remitter, where remitter is defined a priori by HDRS-24 \\<10 post-treatment and a reduction of greater than or equal to 50% in HDRS-24 pre-to-post treatment). Outcome measure is reported as percent accuracy, sensitivity, or specificity in predicting remitter status outcomes.'}], 'secondaryOutcomes': [{'measure': 'Group Differences in 5-HTT Binding Potential', 'timeFrame': '8 Weeks', 'description': 'Differences in mean of 5-HTT binding potential between patients with depression pre-treatment, post-treatment, compared to healthy volunteers. Broadly, binding potential is defined as the ratio of the tracer concentration in tissue to the free plasma concentration. It is a measure of the density of "available" targets (e.g. 5-HTT) \\& the affinity of the ligand (tracer) to that target.'}, {'measure': 'Group Differences in 5-HT1A Binding Potential', 'timeFrame': '8 Weeks', 'description': 'Differences in mean of 5-HT1A binding potential between patients with depression pre-treatment, post-treatment, compared to healthy volunteers. Broadly, binding potential is defined as the ratio of the tracer concentration in tissue to the free plasma concentration. It is a measure of the density of "available" targets (e.g. 5-HT1A) \\& the affinity of the ligand (tracer) to that target.'}, {'measure': 'Relationship Between Change in 5-HTT or 5-HT1A Binding Potential Pre- to Post Treatment and Lithium Treatment Response', 'timeFrame': '8 weeks', 'description': 'Linear regression \\& correlation to assess the relationship between between change in binding potential pre- to post treatment vs. treatment response'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['bipolar disorder', 'bipolar depression', 'serotonin transporter', 'serotonin receptors', 'binding potential', 'brain imaging', 'unipolar depression'], 'conditions': ['Bipolar Disorder', 'Bipolar Depression', 'Unipolar Depression']}, 'referencesModule': {'references': [{'pmid': '32055965', 'type': 'DERIVED', 'citation': 'Ananth M, Bartlett EA, DeLorenzo C, Lin X, Kunkel L, Vadhan NP, Perlman G, Godstrey M, Holzmacher D, Ogden RT, Parsey RV, Huang C. Prediction of lithium treatment response in bipolar depression using 5-HTT and 5-HT1A PET. Eur J Nucl Med Mol Imaging. 2020 Sep;47(10):2417-2428. doi: 10.1007/s00259-020-04681-6. Epub 2020 Feb 13.'}]}, 'descriptionModule': {'briefSummary': 'The primary aims of this study are to:\n\n1. Quantify serotonin transporter (5-HTT) binding potential (BP) in vivo in bipolar disorder patients (BPD) during a major depressive episode (MDE).\n2. Assess the effect of lithium treatment of bipolar disorder on 5-HTT.\n3. Assess the effect of lithium treatment of bipolar disorder on 5-HT1A BP.\n4. Assess the effect of lamotrigine treatment of bipolar disorder on 5-HTT and 5-HT1A BP.\n5. Assess the effect of lithium treatment of unipolar depression on 5-HTT BP.', 'detailedDescription': 'PET and MRI imaging will be used to investigate the aims described above in patients who have bipolar disorder or unipolar depression and are currently experiencing a depressive episode. Both healthy controls and depressed participants with bipolar disorder or unipolar depression will be recruited. Patients who are on medication before enrolling in the study will have a three week washout. At baseline, healthy controls and patients will have an MRI consisting of both structural and functional sequences. Psychological measures will also be obtained at baseline. Within one week of the MRI, both patients and healthy controls will have one CUMI and one DASB PET scan.\n\nFollowing the baseline PET scans, patient participants will begin medication treatment with either lithium or lamotrigine, based on the clinical judgement of the treating psychiatrist. Psychological measures will be obtained every 2 weeks. After 6 weeks of medication treatment at a therapeutic dose, patients will be assessed for remission (defined as a 50% decrease in the HDRS score from baseline). If this criteria is met, patient participants will then have follow-up PET scans (one CUMI and one DASB). If this criteria is not met, the patient will be switched to the other medication under study and will be reevaluated after an additional 4 weeks of medication treatment. Patients who still do not demonstrate a 50% decrease in their HDRS will be considered non-responders and will have repeat CUMI and DASB scans.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'PATIENTS\n\nBIPOLAR\n\nInclusion Criteria:\n\n* Bipolar patients suffering from a major depressive episode currently or recently (in the month prior to scanning). Patients on psychiatric medication will have failed their current regimen for the treatment of their depression: they will meet criteria for depression, be seeking treatment for it, and have been on an adequate dose of antidepressant or mood stabilizer (as defined by the Antidepressant Treatment Form-see Oquendo et al., 2003) for 4 weeks or more.\n* Of sufficient severity to score at least 15 on the first 17 items of the Hamilton Depression Rating Scale or a score of 10 to 14 on the first 17 items of the Hamilton Depression Scale in conjunction with a score of at least 29 on the Beck Depression Inventory.\n* Age range 18-65 years.\n* Off all psychotropic and other types of drugs likely to interact with serotonin transporters and 5-HT1A receptors for at least 21 days. Allowed short-acting benzodiazepines for distressing anxiety or insomnia (up to 24 hours prior to each PET scan). Patients will be off neuroleptics for 3 weeks and off fluoxetine for 6 weeks prior to study. Off serotonin depleting drugs such as reserpine for 3 months. Patient will also be off anti-coagulant/anti-platelet treatment such as coumadin, with the exception of aspirin for 10 days.\n* Willing to travel for PET scanning\n\nExclusion Criteria:\n\n* Other major psychiatric disorders such as schizophrenia, schizoaffective illness; current drug or alcohol abuse (within past 2 months), or drug or alcohol dependence \\<6mos ago; anorexia nervosa or bulimia nervosa in the past year; IV drug use or ecstasy use more than two times.\n* A first-degree family history of schizophrenia if the subject is less than 33 years old (mean age of onset for schizophrenia plus two standard deviations).\n* Significant active physical illness particularly those that may affect the brain or serotonergic system including blood dyscrasias lymphomas, hypersplenism, endocrinopathies, renal failure or chronic obstructive lung disease, autonomic neuropathies, peripheral vascular disease, diabetes, low hemoglobin and malignancy, significant anemic disease or blood loss and the lab parameters platelet count \\< 80,000.\n* Lacks capacity to consent.\n* Actively suicidal-begins expressing a plan for suicide during the washout phase or develop suicidal ideation that warrants admission or requires medication or treatment intervention.\n* Electroconvulsive therapy (ECT) within the past 6 months.\n* Pregnancy, currently lactating; planning to conceive during the course of study participation or abortion in the past two months.\n* Metal implants, pacemaker or metal prostheses or orthodontic appliances, the presence of shrapnel\n* Current, past or anticipated exposure to radiation, that may include: being badged for radiation exposure in the workplace, participation in nuclear medicine procedures, including research protocols in the last year.\n* A neurological disease or loss of consciousness for more than a few minutes\n* Medicinal Patch (participants will be asked to remove before MRI)\n* Patients who are responding satisfactorily to psychiatric medications, because they will not be washed-out for purposes of this study\n* A documented history of a lack of response to a trial of adequate dose and duration of both lithium and lamotrigine defined as minimal clinical response to lamotrigine 200 mgs for at least 4 weeks or lithium serum levels of at least 0.8 (or dose \\>= 900 mgs) for at least 4 weeks.\n* Patient is unlikely to be able to tolerate medication washout\n* Claustrophobia\n* Blood donation within 8 weeks of the start of the study.\n* History of bleeding disorder or are currently taking anticoagulants.\n\nUNIPOLAR\n\nInclusion:\n\n* Unipolar patients suffering from a major depressive episode currently or recently (in the month prior to scanning). Patients on psychiatric medication will have failed their current regimen for the treatment of their depression: they will meet criteria for depression, be seeking treatment for it, and have been on an adequate dose of antidepressant or mood stabilizer (as defined by the Antidepressant Treatment Form-see Oquendo et al., 2003) for 4 weeks or more.\n* Of sufficient severity to score at least 15 on the first 17 items of the Hamilton Depression Rating Scale or a score of 10 to 14 on the first 17 items of the Hamilton Depression Scale in conjunction with a score of at least 29 on the Beck Depression Inventory.\n* Age range 18-65 years.\n* Off all psychotropic and other types of drugs likely to interact with serotonin transporters and 5-HT1A receptors for at least 21 days. Allowed short-acting benzodiazepines for distressing anxiety or insomnia (up to 24 hours prior to each PET scan). Patients will be off neuroleptics for 3 weeks and off fluoxetine for 6 weeks prior to study. Off serotonin depleting drugs such as reserpine for 3 months. Patient will also be off anti-coagulant/anti-platelet treatment such as coumadin, with the exception of aspirin for 10 days.\n* Willing to travel for PET scanning\n\nExclusion:\n\n* Other major psychiatric disorders such as schizophrenia, schizoaffective illness; current drug or alcohol abuse (within past 2 months), or drug or alcohol dependence \\<6mos ago; anorexia nervosa or bulimia nervosa in the past year; IV drug use or ecstasy use more than two times.\n* A first-degree family history of schizophrenia if the subject is less than 33 years old (mean age of onset for schizophrenia plus two standard deviations).\n* Significant active physical illness particularly those that may affect the brain or serotonergic system including blood dyscrasias lymphomas, hypersplenism, endocrinopathies, renal failure or chronic obstructive lung disease, autonomic neuropathies, peripheral vascular disease, diabetes, low hemoglobin and malignancy, significant anemic disease or blood loss and the lab parameters platelet count \\< 80,000.\n* Lacks capacity to consent.\n* Actively suicidal-begins expressing a plan for suicide during the washout phase or develop suicidal ideation that warrants admission or requires medication or treatment intervention.\n* Electroconvulsive therapy (ECT) within the past 6 months.\n* Pregnancy, currently lactating; planning to conceive during the course of study participation or abortion in the past two months.\n* Metal implants, pacemaker or metal prostheses or orthodontic appliances, the presence of shrapnel\n* Current, past or anticipated exposure to radiation, that may include: being badged for radiation exposure in the workplace, participation in nuclear medicine procedures, including research protocols in the last year.\n* A neurological disease or loss of consciousness for more than a few minutes\n* Medicinal Patch (participants will be asked to remove before MRI)\n* Patients who are responding satisfactorily to psychiatric medications, because they will not be washed-out for purposes of this study\n* A documented history of a lack of response to a trial of adequate dose and duration of both lithium and lamotrigine defined as minimal clinical response to lamotrigine 200 mgs for at least 4 weeks or lithium serum levels of at least 0.8 (or dose \\>= 900 mgs) for at least 4 weeks.\n* Patient is unlikely to be able to tolerate medication washout\n* Claustrophobia\n* Blood donation within 8 weeks of the start of the study.\n* History of bleeding disorder or are currently taking anticoagulants.\n* Past unsuccessful treatment of Lithium of adequate dose and duration.\n\nHEALTHY CONTROLS\n\nInclusion:\n\n* No lifetime history of Axis I disorders\n* Age range 18-65 years.\n* Willing to travel for PET scanning.\n\nExclusion:\n\n* Past or present alcohol/substance abuse or dependence; IV drug use or ecstasy use more than two times.\n* A first-degree relative with history of major depression, schizophrenia, schizoaffective disorder, or suicide attempt; two or more first degree relatives with a history of substance dependence.\n* Significant active physical illness particularly those that may affect the brain or serotonergic system including blood dyscrasias lymphomas, hypersplenism, endocrinopathies, renal failure or chronic obstructive lung disease, autonomic neuropathies, peripheral vascular disease, diabetes, low hemoglobin and malignancy, significant anemic disease or blood loss, and the following lab parameters: platelet count \\< 80,000\n* Lacks capacity to consent\n* Pregnancy, currently lactating; planning to conceive during the course of study participation or abortion in the past two months\n* Metal implants, pacemaker or metal prostheses or orthodontic appliances, the presence of shrapnel\n* Current, past or anticipated exposure to radiation, that may include: being badged for radiation exposure in the workplace, participation in nuclear medicine procedures, including research protocols in the last year.\n* A neurological disease or loss of consciousness for more than a few minutes\n* Medicinal Patch (participants will be asked to remove before MRI)\n* Subjects on drugs or medication that affect the serotonin system\n* Claustrophobia\n* Blood donation within 8 weeks of the start of the study.\n* History of bleeding disorder or are currently taking anticoagulants.'}, 'identificationModule': {'nctId': 'NCT01880957', 'briefTitle': 'PET and MRI Brain Imaging of Bipolar Disorder', 'organization': {'class': 'OTHER', 'fullName': 'Stony Brook University'}, 'officialTitle': 'Pathophysiology and Treatment of Bipolar Disorder as Assessed by in Vivo Imaging', 'orgStudyIdInfo': {'id': '2012-1826-F'}, 'secondaryIdInfos': [{'id': '7R01MH090276-03', 'link': 'https://reporter.nih.gov/quickSearch/7R01MH090276-03', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'OTHER', 'label': 'Lithium', 'description': 'Patients in this condition will receive lithium administered as follows: Day 1, 2 and 3, 300 mg bid; Days 4-7 lithium 300 qam and 600 qhs. Lithium level will be checked as close to Day 7 as possible and titrated to a therapeutic plasma level of 0.8-1.2 mEq/l. Subjects will not undergo lithium monotherapy if they have a documented history of at least two failed trials of lithium of at least 4 weeks duration with therapeutic blood levels for a major depressive episode', 'interventionNames': ['Drug: Lithium']}, {'type': 'OTHER', 'label': 'Lamotrigine', 'description': 'Patients who have not respond to adequate prior lithium treatment while depressed, or who refuse lithium, will be given lamotrigine. Lamotrigine will be started at 25 mg bid and increased to 50 mg bid after 2 weeks and again increased to 100 mg bid after an additional 2 weeks.', 'interventionNames': ['Drug: Lamotrigine']}], 'interventions': [{'name': 'Lithium', 'type': 'DRUG', 'otherNames': ['lithium carbonate'], 'armGroupLabels': ['Lithium']}, {'name': 'Lamotrigine', 'type': 'DRUG', 'otherNames': ['Lamictal'], 'armGroupLabels': ['Lamotrigine']}]}, 'contactsLocationsModule': {'locations': [{'zip': '11794', 'city': 'Stony Brook', 'state': 'New York', 'country': 'United States', 'facility': 'Stony Brook University Hospital', 'geoPoint': {'lat': 40.92565, 'lon': -73.14094}}], 'overallOfficials': [{'name': 'Ramin Parsey, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Stony Brook University'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Stony Brook University', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Institute of Mental Health (NIMH)', 'class': 'NIH'}, {'name': 'The Dana Foundation', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor and Chair of the Department of Psychiatry and Director of Positron Emission Tomography (PET) Research', 'investigatorFullName': 'Ramin Parsey', 'investigatorAffiliation': 'Stony Brook University'}}}}