Clinical Medication Development for Bipolar Disorder and Alcohol Use Disorders

NCT02582905 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 072014-005
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Alcohol Use Disorder; Bipolar Disorder; Schizoaffective Disorder Bipolar Type

Keywords

Alcohol Use Disorder; Bipolar Disorder; Mood; Alcohol craving; Pregnenolone; Citicoline

Outcome Measures

Primary Outcomes (1)

• Baseline-to-Exit Change in Drinks Per Drinking Day (TLFB)

  The Timeline Follow Back (TLFB) - Alcohol is a clinician-completed assessment calendar that allows for an estimate of an individual's daily drinking habits over time (i.e., "prior 30 days" at baseline and "since last visit" during the study). Drinks per drinking day is calculated as the average number of standard drinks consumed, per each day indicated as a day during which alcohol was consumed, adjusted for the period of time being assessed (e.g., 30 days at baseline). Baseline-to-Exit Change in Drinks per Drinking Day (TLFB) was calculated as Drinks/Drinking Day (Exit) - Drinks/Drinking Day (Baseline), with negative scores indicating a decrease in the number of drinks per drinking day. The TLFB (Timeline Followback) is a method of assessment of alcohol consumption and is not a scale with minimum and maximum values.

  12 weeks

Secondary Outcomes (1)

• Examine the Use of an Adaptive Design in a Clinical Trial for Alcohol Use Disorder.

  Study Month 30

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Matching placebo given beginning at 1 capsule twice daily (BID) increasing to 2 capsules BID at week 1, 3 capsules BID at week 2, and 4 capsules BID at weeks 3-12.

Drug: Placebo

Citicoline

EXPERIMENTAL

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.

Dietary Supplement: Citicoline

Pregnenolone

EXPERIMENTAL

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.

Drug: Pregnenolone

Interventions

Placebo DRUG

Inactive ingredient matching the active comparators in appearance.

Also known as: Sugar pill

Placebo

Citicoline DIETARY_SUPPLEMENT

Citicoline is an over-the-counter nutritional supplement that is used for neuroprotective effects. It is a naturally occurring neurochemical in the human body.

Also known as: CDP-Choline, cytidine diphosphate-choline

Citicoline

Pregnenolone DRUG

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.

Also known as: pregn-5-en-3β-ol-20-one

Pregnenolone

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Sherwood Brown, MD, PhD: lead
• University of Miami: collaborator
• University of Texas Rio Grande Valley: collaborator

Study Sites (3)

University of Miami

Miami, Florida, 33136, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

The University of Texas Rio Grande Valley

Edinburg, Texas, 78539, United States

Location

MeSH Terms

Conditions

Alcoholism; Bipolar Disorder

Interventions

Sugars; Cytidine Diphosphate Choline; Pregnenolone

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Bipolar and Related Disorders; Mood Disorders

Intervention Hierarchy (Ancestors)

Carbohydrates; Choline; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Cytidine Diphosphate; Cytosine Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Limitations and Caveats

Due to low enrollment, the secondary aim (Examine the use of an adaptive design in a clinical trial for BPD and alcohol use disorder) was untested. Phase 1 of the adaptive design could not be completed as we were unable to enroll n = 99 participants. Therefore, we never reached the point of dropping a group and could not test the design.

Results Point of Contact

• Title: E. Sherwood Brown, MD PhD MBA
• Organization: University of Texas Southwestern Medical Center

sherwood.brown@utsouthwestern.edu

214-645-6950

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Psychiatry

Study Record Dates

• First Submitted: October 20, 2015
• First Posted: October 21, 2015
• Study Start: May 1, 2016
• Primary Completion: May 1, 2023
• Study Completion: May 1, 2023
• Last Updated: October 9, 2024
• Results First Posted: October 9, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)