Acamprosate vs. Placebo in Bipolar Alcoholics

A Double-Blind, Randomized, Placebo-Controlled Trial of Acamprosate in Alcohol-Dependent Individuals With Comorbid Bipolar Disorder

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00466661

Enrollment

Registered

2007-04-27

Start date

2007-04-30

Completion date

2010-02-28

Last updated

2018-12-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Alcohol Dependence, Bipolar Disorder

Keywords

Acamprosate, Alcoholism, Bipolar disorder, Comorbidity, Craving, Depression, GABA, Glutamate, Mania, Pharmacotherapy, Withdrawal

Brief summary

To conduct a double-blind, randomized, placebo-controlled outpatient clinical trial of acamprosate in individuals with alcohol dependence and bipolar disorder who are also receiving mood stabilizing medication. The study will assess the safety and efficacy of acamprosate in alcohol-dependent bipolar patients as measured by its effects on alcohol use and mood symptoms relative to placebo. The primary hypothesis to be tested is whether individuals with comorbid bipolar disorder and alcohol dependence who receive acamprosate plus mood stabilizer will have greater improvement in alcohol-related outcomes than those who receive mood stabilizer alone. A secondary hypothesis that will be explored is that alcohol-dependent bipolar individuals treated with acamprosate will have greater mood stability as compared to those treated with mood stabilizers alone.

Interventions

DRUGAcamprosate

666 mg po TID

DRUGPlacebo

2 tabs po TID

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

1. Adults ages 18-65 2. Meet DSM-IV criteria for current (past 90 days) alcohol dependence 3. Meet DSM-IV criteria for bipolar I or bipolar II disorder 4. Currently on a mood stabilizing medication regimen, including the use of lithium, valproic acid, lamotrigine, carbamazepine, and/or antipsychotic agent FDA approved to treat bipolar disorder without any dosage adjustments in the past 30 days 5. Must be able to remain free from alcohol for at least 3 days prior to medication initiation 6. Subjects must be able to adequately provide informed consent and function at an intellectual level sufficient to allow the accurate completion of all assessment instruments 7. Subjects must consent to random assignment and be willing to commit to medication treatment and follow-up assessments

Exclusion criteria

1. Individuals with a primary psychiatric disorder other than bipolar disorder 2. Individuals with an uncontrolled neurologic condition that could confound the results of the study 3. Individuals with an uncontrolled medical condition that may adversely affect the conduct of this trial or jeopardize the subject's safety 4. Participants with creatinine clearance less than or equal to half of normal value as indicated by chem. 7 results conducted at screening visit. 5. Concomitant use of other psychotropic medications not allowed per the protocol 6. Women of childbearing potential who are pregnant, lactating or refuse to use adequate forms of birth control 7. Current suicidal or homicidal risk 8. Baseline scores of \> 35 on the Montgomery Asberg Depression Rating Scale and/or \> 25 on the Young Mania Rating Scale

Design outcomes

Primary

Measure	Time frame	Description
Time to First Drink (Days)	8 weeks	Number of days after randomization until consumption of first alcoholic beverage per self-report.

Secondary

Measure	Time frame	Description
Percent Heavy Drinking Days	8 weeks	Percentage of drinking days that are heavy drinking days (5 or more standard drinks/day for males, 4 or more standard drinks/day for females)
Percent Carbohydrate-deficient Transferrin	8 weeks	Measured level of validated serum alcohol biomarker
Gamma-glutamyltransferase	8 weeks	Measured levels of validated serum alcohol biomarker
Percent Days Abstinent	8 weeks	Percentage of days in trial with no alcohol consumption
Montgomery Asberg Depression Rating Scale Score	8 weeks	MADRS scores at study endpoint. Higher scores indicate a worse outcome. Minimum score = 0, maximum score = 60.
Young Mania Rating Scale Score	8 weeks	YMRS scores at study endpoint. Higher scores indicate a worse outcome. Minimum score = 0, maximum score = 60.
Clinical Global Impression Scale Score	8 weeks	Higher values indicate worse outcomes; minimum value = 1, maximum value = 7
Obsessive Compulsive Drinking Scale Score	8 weeks	Higher scores indicate worse outcome; minimum score = 0, maximum score = 40

Countries

United States

Participant flow

Recruitment details

Recruitment by clinical referral

Pre-assignment details

Two week lead-in (Screening, Baseline)

Participants by arm

Arm	Count
Acamprosate 666 mg p.o. TID	16
Placebo Matching placebo	17
Total	33

Baseline characteristics

Characteristic	Acamprosate	Placebo	Total
Age, Continuous	40.8 years STANDARD_DEVIATION 6.7	43.7 years STANDARD_DEVIATION 11.3	42.1 years STANDARD_DEVIATION 9.3
Region of Enrollment United States	16 participants	17 participants	33 participants
Sex: Female, Male Female	6 Participants	8 Participants	14 Participants
Sex: Female, Male Male	10 Participants	9 Participants	19 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 14	0 / 16
other Total, other adverse events	6 / 14	8 / 16
serious Total, serious adverse events	3 / 14	3 / 16

Outcome results

Primary