Last updated on March 2018

Clinical Medication Development for Bipolar Disorder and Alcohol Use Disorders


Brief description of study

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.

Detailed Study Description

A 12-week, randomized, double-blind, parallel-group, placebo-controlled adaptive, Drop The Loser (DTL) design clinical trial of citicoline and pregnenolone will be conducted in 199 outpatients with bipolar I or II disorder or schizoaffective disorder (bipolar type) and current alcohol use disorder. Potential participants will be identified and an appointment will be arranged. At this appointment, informed consent will be obtained, and assessment procedures, including a review of inclusion and exclusion criteria, will be performed.

A structured clinical interview for Diagnostic Statistical Manual (DSM-5), Structured Clinical Interview for Disorders (SCID) will be performed to establish the diagnoses of bipolar I or II disorder and alcohol use disorder. Recent alcohol use (and, if present, other substance use) will be assessed using the Timeline Followback (TLFB) method. Drinking severity and withdrawal symptoms will be assessed through a variety of measures (e.g., Clinical Institute Withdrawal Assessment of Alcohol Use-Revised (CIWA-Ar), Penn Alcohol Craving Scale (PACS), Short Index of Problems (SIP)). Length of problem alcohol use will be assessed by asking "When did alcohol first start causing you problems?" Blood will be drawn for laboratory analyses including a complete blood count (CBC) and Comprehensive Metabolic Panel (includes a liver panel with AST, ALT as well as lipids and electrolytes), and GGT and carbohydrate-deficient transferrin (CDT) will be added at baseline (week 0) and weeks 6 and 12. Cognition, including the domains of memory, decision making, impulsivity, attention, and executive functioning will also be assessed at baseline and week 12 using the World Health Organization/University of California at Los Angeles Auditory-Verbal Learning Test (WHO-UCLA AVLT), Trail Making Test (TMT), and the Golden Stroop Color Word Test. Women of childbearing potential will receive a urine pregnancy test at baseline, week 6, and week 12 and will be counseled about effective contraceptive methods. A psychiatrist (PI or Co-I) will assess participants at baseline and weekly follow-up visits and will participate in the informed consent process. The active medication or placebo capsules will be initiated at baseline and increased weekly in weeks 1, 2 and 3 to achieve the target doses for citicoline (2000 mg/day) or pregnenolone (500 mg/day). Side effects will be managed in a blinded fashion. Safety and side effects will be assessed with the Systematic Assessment for Treatment Emergent Events (SAFTEE). At weekly visits, mood and suicidality will be assessed through various measures (e.g. Hamilton Rating Scale for Depression (HRSD17), Columbia Suicide Severity Rating Scale (CSSRS) and assessment of alcohol use will again be evaluated. All participants will receive Medical Monitoring (MM) as a psychosocial platform. After study completion, participants will be provided standard psychiatric care until outside referral is arranged.

Clinical Study Identifier: NCT02582905

Contact Investigators or Research Sites near you

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Ihsan M. Salloum, MD, MPH

University of Miami
Miami, FL United States
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E. Sherwood Brown, M.D., Ph.D.

UT Southwestern Medical Center
Dallas, TX United States
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