Clinical Medication Development for Bipolar Disorder and Alcohol Use Disorders
|Alcohol Use Disorder Bipolar Disorder||Drug: Placebo Drug: Citicoline Drug: Pregnenolone||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
|Official Title:||Clinical Medication Development for Bipolar Disorder and Alcohol Use Disorders|
- Timeline Followback (TLFB) [ Time Frame: 12 weeks ]The Timeline Followback is used to assess recent alcohol use (and if present, other substance use).
|Study Start Date:||May 2016|
|Estimated Study Completion Date:||December 2021|
|Estimated Primary Completion Date:||January 2020 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
Matching placebo given beginning at 1 capsule BID increasing to 2 capsules BID at week 1, 3 capsules BID at week 2, and 4 capsules BID at weeks 3-12.
Inactive ingredient matching the active comparators in appearance.
Other Name: Sugar pill
Citicoline will be given beginning at 250 mg BID with an increase to 500 mg BID at week 1, 750 mg BID at week 2, and 1000 mg BID at weeks 3-12.
Citicoline is an over-the-counter nutritional supplement that is used for neuroprotective effects. It is a naturally occurring neurochemical in the human body.
Pregnenolone will be given beginning at 50 mg BID with an increase to 100 mg BID at week 1, 150 mg BID at week 2, and 250 mg BID at weeks 3-12.
Pregnenolone is a naturally occurring neurosteroid that is synthesized from cholesterol in the adrenal glands and also in the brain. Pregnenolone produces other neuroactive steroids.
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, depressed mood state 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02582905
|Contact: Collette B. Bice, MSemail@example.com|
|United States, Florida|
|University of Miami||Recruiting|
|Miami, Florida, United States, 33136|
|Contact: Yamila Carmona, MS 305-243-2686 firstname.lastname@example.org|
|Principal Investigator: Ihsan M. Salloum, MD, MPH|
|United States, Texas|
|UT Southwestern Medical Center||Recruiting|
|Dallas, Texas, United States, 75390|
|Contact: Collette B. Bice, MS 214-645-6954 email@example.com|
|Principal Investigator: E. Sherwood Brown, M.D., Ph.D.|