Ignite Creation Date:
2025-12-25 @ 4:36 AM
Ignite Modification Date:
2026-03-05 @ 1:54 AM
Study NCT ID:
NCT03336918
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-07-02
First Post:
2017-10-05
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Lithium Effects on the Brain's Functional and Structural Connectome in the Treatment of Bipolar Disorder
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001714', 'term': 'Bipolar Disorder'}, {'id': 'D003863', 'term': 'Depression'}], 'ancestors': [{'id': 'D000068105', 'term': 'Bipolar and Related Disorders'}, {'id': 'D019964', 'term': 'Mood Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}, {'id': 'D001526', 'term': 'Behavioral Symptoms'}, {'id': 'D001519', 'term': 'Behavior'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D008094', 'term': 'Lithium'}, {'id': 'D016651', 'term': 'Lithium Carbonate'}, {'id': 'D019343', 'term': 'Citric Acid'}], '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': 'D002951', 'term': 'Citrates'}, {'id': 'D014233', 'term': 'Tricarboxylic Acids'}, {'id': 'D000144', 'term': 'Acids, Acyclic'}, {'id': 'D002264', 'term': 'Carboxylic Acids'}, {'id': 'D009930', 'term': 'Organic Chemicals'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Gene Expression RNA sequencing'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'OTHER'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 120}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2017-12-07', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-06', 'completionDateStruct': {'date': '2025-12-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-06-30', 'studyFirstSubmitDate': '2017-10-05', 'studyFirstSubmitQcDate': '2017-11-06', 'lastUpdatePostDateStruct': {'date': '2025-07-02', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2017-11-08', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-06-30', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Functional Connectivity (Fc) changes', 'timeFrame': '2, 8, 26 weeks', 'description': 'Investigate effects of lithium monotherapy treatment of BD on changes in Fc through fMRI imaging from baseline after 2, 8, and 26 weeks of treatment and test whether these changes correlate with improvement in state-related symptoms and longer term mood stability. Healthy controls will also be scanned at the same time points but not treated.'}, {'measure': 'Structural Connectivity (Sc) changes', 'timeFrame': '2, 8, 26 weeks', 'description': 'Investigate effects of lithium monotherapy treatment of BD depression on changes in the diffusion weighted imaging Sc through fMRI imaging from baseline after 2, 8, and 26 weeks and test whether these changes correlate with depression severity and mood stability. Healthy controls will also be scanned at the same time points but not treated.'}], 'secondaryOutcomes': [{'measure': 'Changes in peripheral gene expression', 'timeFrame': '2, 8, 26 weeks', 'description': 'An exploratory investigation of whether lithium-related changes in the functional and structural connectome over time represent a link between shifts in peripheral gene expression and improvement in illness-related measures.Lithium therapy will be associated with changes in gene expression pathways such as the mitochondrial-carnitine shuttle pathway, which in turn will be related to changes in the functional and structural connectome.'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Bipolar Disorder', 'Bipolar I and II Depression', 'Lithium', 'Depression'], 'conditions': ['Bipolar Disorder', 'Bipolar I Depression', 'Bipolar II Depression', 'Bipolar Depression', 'Depression', 'Major Depressive Episode']}, 'descriptionModule': {'briefSummary': 'Lithium is highly effective in the treatment of bipolar disorder. This study aims to investigate, for the first time, the impact of lithium monotherapy on the structural and functional connectivity of the brain using MRI imaging.', 'detailedDescription': 'The premise of this proposal is that the clinical efficacy of lithium in bipolar disorder, and its complex effects on multiple brain physiological functions, may be best deciphered using a network properties-metric approach. This approach is critical because it provides insight into the function of brain networks (e.g., resilience to disruption, central hubs), which is likely to be more closely linked to behavioral outcomes. Furthermore, we will conduct an exploratory investigation of the in vivo molecular effects of lithium by measuring peripheral gene expression. To bring these together, we will also explore whether connectome changes serve as mediator between molecular changes (i.e., gene expression) induced by lithium treatment and behavioral changes (e.g., depression, mood stability, suicidality).'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '60 Years', 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Bipolar disorder and healthy controls', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion criteria for BD subjects:\n\n* ages 18-60 years (inclusive) and able to give voluntary informed consent;\n* Satisfy criteria for Diagnostic and Statistical Manual 5th edition (DSM-V) for BD I or II, current Depressive Episode;\n* 17-item Hamilton Depression Rating Scale (HAM-D) score \\>15 and \\<25;\n* Young Mania Rating Scale (YMRS) \\< 8;\n* no psychotropics in the last 2 weeks (if previously on fluoxetine then medication free for 5 weeks) OR on stable psychotropic medications for 12 weeks\n* no lithium treatment for past 6 months;\n* satisfy criteria to undergo an MRI scan based on MRI screening questionnaire;\n* able to be managed as outpatients during the study as ascertained by Clinical Global Severity Scale \\< 5 (i.e., moderately ill) and no significant suicidal or homicidal ideation or gross disability.\n\nExclusion criteria for BD subjects are:\n\n* meeting DSM-IV criteria for schizophrenia, schizoaffective disorder, or an anxiety disorder as\n* a primary diagnosis;\n* requiring inpatient treatment;\n* meeting DSM-V criteria for substance dependence within the past 3 months, except caffeine or nicotine;\n* positive urinary toxicology screening at screening visit;\n* use of alcohol in the past 1 week;\n* serious medical or neurological illness;\n* current pregnancy or breast feeding;\n* metallic implants or other contraindications to MRI.\n\nInclusion criteria for healthy subjects:\n\n* ages 18-60 years and ability to give voluntary informed consent;\n* no history of psychiatric illness or substance abuse or dependence;\n* no significant family history of psychiatric or neurological illness in first degree relative;\n* not currently taking any prescription or centrally acting medications;\n* no use of alcohol in the past 1 week;\n* and no serious medical or neurological illness.\n\nExclusion criteria for healthy subjects are:\n\n* under 18 years of age;\n* pregnant or breast-feeding;\n* metallic implants or other contraindication to MRI.'}, 'identificationModule': {'nctId': 'NCT03336918', 'briefTitle': "Lithium Effects on the Brain's Functional and Structural Connectome in the Treatment of Bipolar Disorder", 'organization': {'class': 'OTHER', 'fullName': "Brigham and Women's Hospital"}, 'officialTitle': "Lithium Effects on the Brain's Functional and Structural Connectome in the Treatment of Bipolar Disorder", 'orgStudyIdInfo': {'id': '17-441'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Bipolar Disorder I or II Depressed', 'description': 'DSM-V Bipolar I or II Depressed treated with lithium', 'interventionNames': ['Drug: Lithium']}, {'label': 'Healthy Controls', 'description': 'Healthy Controls with no psychiatric history'}], 'interventions': [{'name': 'Lithium', 'type': 'DRUG', 'otherNames': ['Lithium carbonate or citrate or Lithium extended release'], 'description': 'Open-label lithium treatment for Bipolar Disorder Subjects\n\nHealthy Controls only repeat testing - no intervention', 'armGroupLabels': ['Bipolar Disorder I or II Depressed']}]}, 'contactsLocationsModule': {'locations': [{'zip': '44195', 'city': 'Cleveland', 'state': 'Ohio', 'country': 'United States', 'facility': 'Cleveland Clinic Foundation Center for Behavioral Health', 'geoPoint': {'lat': 41.4995, 'lon': -81.69541}}], 'overallOfficials': [{'name': 'Amit Anand, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'The Cleveland Clinic'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': "Brigham and Women's Hospital", 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal Investigator', 'investigatorFullName': 'Amit Anand', 'investigatorAffiliation': "Brigham and Women's Hospital"}}}}