Treatment of Alcohol Dependence and Comorbid Bipolar Disorder

NCT01015586 | Completed Phase 4 Results DMC

• 2 other identifiers: HR#19550K23AA017666
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

The study will determine if individuals with co-occurring bipolar disorder and alcohol dependence report reduced alcohol consumption, improvement in mood symptoms, and cognitive performance if treated with lamotrigine plus their usual mood stabilizing medications relative to subjects treated with placebo plus usual mood stabilizing medications over a 16 week period.

Conditions

Alcohol Dependence; Bipolar Disorder; Depression; Mania; Psychosis

Keywords

Alcohol; Bipolar Disorder; Manic depression; Addiction; Alcoholism; Cognitive impairment; Executive function; Anxiety; Depression; Mania; Affective disorder; Psychosis; Carbohydrate deficient transferrin; Gammaglutamyltransferase; California Verbal Learning Test; Montgomery Asberg Depression Rating Scale; Young Mania Rating Scale; Timeline Follow Back

Outcome Measures

Primary Outcomes (1)

• Percent Days Abstinent From Alcohol

  Percentage of days in trial without consumption of alcoholic beverages per participant self-report; minimum = 0, maximum = 100; higher numbers indicate better outcome. Percent days abstinent was calculated as: (number of days abstinent per self-report / total number of days in trial)\*100.

  12 weeks

Secondary Outcomes (6)

• Percent Heavy Drinking Days

  12 weeks

• Biomarkers of Alcohol Use: Carbohydrate-deficient Transferrin (CDT)

  12 weeks after randomization

• Biomarkers of Alcohol Use: Gamma-glutamyltransferase (GGT)

  12 weeks after randomization

• Montgomery-Asberg Depression Rating Scale (MADRS) Score

  Baseline and 12 weeks

• Young Mania Rating Scale (YMRS) Scores

  Baseline and 12 weeks

Study Arms (2)

Lamotrigine

EXPERIMENTAL

Add-on lamotrigine plus pre-existing mood stabilizing medication regimen. Active fixed-dose drug titration from 25-200 mg/day over first six weeks, 200 mg/day fixed-dose maintenance for second six weeks

Drug: Lamotrigine

Placebo

PLACEBO COMPARATOR

Add-on placebo plus pre-existing mood stabilization regimen for 12 weeks

Drug: Placebo

Interventions

Lamotrigine DRUG

Six week titration from 25 mg/day to 200 mg/day, then 200 mg/day maintenance for additional six weeks

Lamotrigine

Placebo DRUG

Placebo once daily for 12 weeks

Placebo

Eligibility Criteria

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

You may qualify if:

• Age 18-65
• Meet DSM-IV-TR criteria for current alcohol dependence with active alcohol use in the past 30 days
• Meet DSM-IV-TR criteria for bipolar I or bipolar II disorder
• Have average alcohol consumption of at least 35 drinks/week for men, 28 drinks/week for women in the last 4 weeks of active drinking prior to enrollment.
• Able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of the assessment instruments.
• Must consent to random assignment and be willing to commit to medication treatment and follow-up assessments.
• Currently under the care of a psychiatrist.
• Must consent to sign a release of information allowing investigators to communicate with his/her psychiatrist to verify treatment history and facilitate care should treatment-emergent psychiatric symptoms develop during the trial.
• Currently taking a therapeutic dosage of one or more mood stabilizing medications as defined by one or more of the following:
• Lithium level of 0.6 - 1.2 mEq/L
• Prescribed daily use of first generation antipsychotic agents including chlorpromazine, fluphenazine, or haloperidol or their injectible depot (decanoate) equivalents at a dose adequate to maintain clinical stability as documented by the subject's outpatient psychiatric provider c) Prescribed daily use of second generation antipsychotic agents including olanzapine, risperidone, paliperidone, quetiapine, aripiprazole, or ziprasidone or their injectible depot equivalent at a dose adequate to maintain clinical stability as documented by the subject's outpatient psychiatric provider
• Stable psychiatric symptoms as defined by no changes to psychotropic drug regimen for 30 days
• Must agree to identify collateral individuals for contact to facilitate follow-up appointments

You may not qualify if:

• A primary psychiatric diagnosis other than bipolar disorder
• Any uncontrolled neurologic condition (e.g. epilepsy) that could confound the results of the study
• Any history of Stevens-Johnson syndrome or other severe rash requiring hospitalization
• Any history of head injury with loss of consciousness greater than 30 minutes
• Any history of learning disability, alcoholic dementia, or electroconvulsive therapy in the past 3 months
• Any uncontrolled medical condition that may adversely affect the conduct of the trial or jeopardize the safety of the subject
• Plasma levels of liver transaminases (AST, ALT) greater than 3 times the normal range
• Concomitant use of valproic acid
• Concomitant use of carbamazepine, oxcarbazepine, phenytoin, primidone, or phenobarbital
• Concomitant use of disulfiram, naltrexone, acamprosate, or topiramate
• Concomitant use of benzodiazepines or any other medications not allowed per the protocol
• Women of childbearing potential who are pregnant, lactating, or refuse adequate forms of contraception
• Current suicidal or homicidal risk
• Baseline scores of more than 35 on the Montgomery-Asberg Depression Rating Scale or more than 16 on the Young Mania Rating Scale

Sponsors & Collaborators

• Medical University of South Carolina: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

Clinical Neuroscience Division, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

MeSH Terms

Conditions

Alcoholism; Bipolar Disorder; Depression; Mania; Psychotic Disorders; Behavior, Addictive; Cognitive Dysfunction; Anxiety Disorders; Mood Disorders

Interventions

Lamotrigine

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Bipolar and Related Disorders; Behavioral Symptoms; Behavior; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Schizophrenia Spectrum and Other Psychotic Disorders; Compulsive Behavior; Impulsive Behavior; Cognition Disorders; Neurocognitive Disorders

Intervention Hierarchy (Ancestors)

Triazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Relatively small sample size, suboptimal retention rate (58% of all randomized subjects)

Results Point of Contact

• Title: Bryan K. Tolliver, MD PhD
• Organization: Medical University of South Carolina

tollive@musc.edu

843-792-4869

Study Officials

• Bryan K Tolliver, MD, PhD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

• Kathleen T Brady, M.D., Ph.D.

  Medical University of South Carolina

  STUDY DIRECTOR

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

Study Record Dates

• First Submitted: November 17, 2009
• First Posted: November 18, 2009
• Study Start: February 1, 2010
• Primary Completion: May 1, 2014
• Study Completion: September 1, 2014
• Last Updated: January 9, 2019
• Results First Posted: January 9, 2019

Record last verified: 2019-01

Locations

US (1)