Clinical Medication Development for Bipolar Disorder and Alcohol Use Disorders

Investigator: Ihsan Salloum

Institutional Protocol #: 20150701

National Clinical Trials Identifier: NCT02582905

Funding Agency/Sponsor: National Institute on Alcohol Abuse and Alcoholism

Division: Psychiatry

Therapeutic Area: Other

Phase: Phase I/II

Enrolling Sites: University of Miami Medical Group

Enrolling Since: 3/26/2016


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, mood state currently depressed. 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.

Eligibility Criteria:

Inclusion Criteria:

- Outpatient men and women age 18-65 years old with bipolar I or II disorder (currently

- English or Spanish speaking

- Current diagnosis of alcohol use disorder with at least moderate severity (DSM-5

- Alcohol use of at least 28 drinks a week if male or an average of 21 drinks per week
if female and 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 but anxiety disorders will be

- Baseline HRSD17 or YMRS scores ≥ 35 to exclude those with very severe mood symptoms at

- Evidence of clinically significant alcohol withdrawal symptoms defined as a CIWA-Ar
score of ≥ 10

- Current (last 28 days) treatment with naltrexone, acamprosate, disulfiram, topiramate
or 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

Gender: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Accepts healthy volunteers: No

Please note that this is written for scientific review, and if there are any questions or clarifications needed, please contact

Yamila Carmona, Sr. Clinical Research Coordinator
(305) 243 2686


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