Clinical Medication Development for Bipolar Disorder and Alcohol Use Disorders

072014-005

Preclinical and clinical data as well as mechanistic justification have been presented suggesting citicoline and pregnenolone are each promising treatments for alcohol use in BPD. Both appear to have favorable side effect profiles and no known drug-drug interactions. Thus, they have the potential to be safely used in a dual diagnosis population already taking other medications. A 12-week, randomized, double-blind, parallel-group, placebo-controlled adaptive design study of citicoline and pregnenolone is proposed in 199 persons with alcohol use disorder and bipolar I or II disorder or schizoaffective disorder (bipolar type). The primary aim will be to assess change in alcohol use. Biomarkers of alcohol use, alcohol craving, mood and cognition will also be assessed. Relationships between neurosteroid and choline levels and the outcome measures will be explored.

2016-05-01

2023-05-01

2023-05-01

Completed

Early phase I

96

Inclusion Criteria: * Outpatient men and women age 18-70 years old with bipolar I or II disorder or schizoaffective disorder (bipolar type) * English or Spanish speaking * Current diagnosis of alcohol use disorder with at least moderate severity (DSM-5 terminology) * Alcohol use of at least an average of 28 drinks a week if male or an average of 21 drinks per week if female and an average of 3 drinking days a week in the 28 days prior to intake * Current mood stabilizer therapy (defined as lithium, lamotrigine, carbamazepine, oxcarbazepine or an atypical antipsychotic) with stable dose for ≥ 28 days prior to randomization or valproate/divalproex at a stable dose for ≥ 90 days (longer period due to data suggesting valproate may decrease alcohol use in BPD) * Diagnosis of substance use disorder other than alcohol, caffeine or nicotine is allowed if 1) alcohol is the self-identified substance of choice and 2) severity of other substance use disorder is ≤ moderate Exclusion Criteria: * Mood disorders other than bipolar I or II disorders or schizoaffective disorder bipolar type (e.g. bipolar NOS, cyclothymic disorders, schizophrenia, schizoaffective disorder depressive type, or unipolar depression based on the SCID); other disorders (e.g. anxiety, will be allowed) * Baseline HRSD17 or YMRS scores ≥ 35 to exclude those with very severe mood symptoms at baseline * Evidence of clinically significant alcohol withdrawal symptoms defined as a CIWA-Ar score of ≥ 10 * Current (last 28 days) treatment with naltrexone, acamprosate, disulfiram, or topiramate as these may also decrease alcohol use * Oral contraceptives and hormone replacement therapy. This exclusion is due to a possible interaction with pregnenolone. * Women with hormone sensitive conditions such as breast cancer, uterine cancer, ovarian cancer, endometriosis, uterine fibroids. These persons are excluded because pregnenolone is converted to estrogens. * Vulnerable populations (e.g. pregnant, nursing, cognitively impaired, incarcerated) * High risk for suicide defined as \> 1 attempt in past 12 months that required medical attention, any attempt in the past 3 months or current suicidal ideation with plan and intent such that outpatient care is precluded * Intensive outpatient treatment (defined as ≥3 visits each week) for substance abuse (AA, NA meetings, or less intensive counseling at baseline will be allowed) * Severe/unstable condition (e.g. cirrhosis, poorly controlled hypertension) or laboratory/physical exam findings consistent with serious illness (e.g. abnormal electrolytes) or AST or ALT \>3 times normal

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 96, 'type': 'ACTUAL'}}

2023-10-03