New Medications to Treat Alcohol Dependence

NCT00223639 | Completed Phase 2 DMC

• 1 other identifier: 5R01AA014628-02
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief Summary

In the last decade, there has been an explosion of new knowledge of the neuroscientific basis of alcohol-seeking behavior. Briefly, medications that modulate mesolimbic dopamine pathways by facilitating gamma amino butyric function and inhibiting the action of excitatory amino acids should reliably diminish alcohol's rewarding effects. Topiramate (a sulfamate-substituted fructo-pyranose derivative) has these characteristics. In support of this concept, we have shown in a phase-II-type medications clinical trial that topiramate is significantly superior to placebo at improving drinking outcomes and decreasing craving among (N = 150) alcohol-dependent individuals. Using the carefully controlled environment of the human laboratory, we are submitting a revised application containing a set of systematic studies to assess directly the mechanistic neuropharmacological processes that are associated with topiramate's anti-drinking effects. This will provide a more comprehensive understanding of the neurobiology of alcohol-seeking behavior and aid in the development of even more effective compounds for the treatment of alcohol dependence. Thus, the specific aims of the project are to: 1) determine the dose-relationship of acute effects of topiramate to reduce alcohol effects related to its abuse and addiction potential. We hypothesize that topiramate will reduce alcohol-induced craving, reward, and euphoria; 2) determine whether chronic treatment with an acutely effective dose of topiramate produces substantial reductions in alcohol-related cue-induced craving, thereby decreasing the potential for treatment relapse. We hypothesize that chronic topiramate administration will desensitize (reduce) alcohol craving produced by alcohol-related sensory cues; and 3) determine whether topiramate interactions with and without alcohol are associated with neurocognitive impairment. Clinical studies including ours have suggested that topiramate use may be associated with neurocognitive effects such as loss of concentration and memory impairment. In our own study, these effects were mild and not associated with reduced treatment compliance. Since alcohol's ability to produce neurocognitive impairment may be mediated through similar ionic mechanisms to that of topiramate, the proposed human laboratory setting affords us the unique opportunity to more clearly delineate topiramate's neurocognitive effects in both the presence and absence of alcohol. This study supports NIAAA's goal to develop effective medications for treating alcoholism and to understand the basic underpinnings of the disease.

Conditions

Alcoholism

Keywords

alcoholism /alcohol abuse; alcoholism antagonist; anticonvulsant; cognition; neuropharmacology; substance abuse related behavior; craving; euphoria; relapse /recurrence; patient oriented research

Outcome Measures

Primary Outcomes (1)

• Reduction of alcohol-induced craving,reward,and euphoria

  During testing days

Secondary Outcomes (2)

• Reductions in alcohol-related cue-induced associated with relapse

  During testing days

• Determine whether topiramate interactions with and without alcohol are associated with neurocognitive impairment

  During testing days

Study Arms (2)

Topiramate

EXPERIMENTAL

Drug: Topiramate

Placebo

PLACEBO COMPARATOR

Drug: Topiramate

Interventions

Topiramate DRUG

200mg twice a day

Also known as: Topamax

Placebo; Topiramate

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• DSM-IV-R diagnosis of alcohol dependence.
• Drinking on average ≥14 and ≥21 drinks/week in the 30 days prior to enrollment for women and men, respectively, and describing a liking for and frequent use of beer as the alcohol-containing beverage.

You may not qualify if:

• Negative pregnancy test at intake. Women of childbearing potential will be placed on oral contraceptives and also will be expected to use barrier and spermicide as an additional form of contraception if sexually active.
• Literate in English language, and able to read, understand, and complete rating scales and questionnaires accurately.
• Willingness to comply with study procedures and protocol including agreement to overnight stay at the human laboratory. Compliance with the alcohol, tobacco, and drug-free environment regulations at the human laboratory is also a condition of enrollment.
• Written informed consent.
• Expression of desire for immediate treatment for alcohol or drug addiction.
• History of mental illness that warrants treatment or would preclude safe participation in the protocol except nicotine dependence, as determined by mental status and psychiatric interview using the Structured Clinical Interview for DSM-IV.
• Acute or chronic organic brain syndrome, schizophrenia, bipolar disorder, or any psychotic disorder.
• Significant medical illness (including hypertension) as determined by history and/or complete physical examination.
• Uncontrolled uterine or cervical bleeding.
• History of blood clots.
• Past problems with oral contraceptive pills.
• Gross neurological disease.
• Mental retardation.
• Neurocognitive functioning \>1.5 standard deviation below expected range
• Clinically significant abnormalities on the electrocardiogram that will preclude safe participation.

Sponsors & Collaborators

• Bankole Johnson: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (2)

UVA CARE

Charlottesville, Virginia, 22911, United States

Location

UVA CARE Richmond

Richmond, Virginia, 23294, United States

Location

MeSH Terms

Conditions

Alcoholism; Recurrence

Interventions

Topiramate

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Study Officials

• Bankole A Johnson, DSc,MD,PhD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chair of Psychiatry and Neurobehavioral Sciences

Study Record Dates

• First Submitted: September 19, 2005
• First Posted: September 22, 2005
• Study Start: September 1, 2005
• Primary Completion: July 1, 2008
• Study Completion: July 1, 2008
• Last Updated: February 7, 2012

Record last verified: 2012-02

Locations

US (2)