Treatment With Mecamylamine in Smoking and Non-smoking Alcohol Dependent Patients

Phase 2

Completed

Conditions: Alcoholism

Interventions: Drug: mecamylamine
Drug: Placebo

Registration Number: NCT00342563

Lead Sponsor: Yale University

Brief Summary: The purpose of the study will be to evaluate the efficacy of mecamylamine in reducing alcohol consumption in smoking and non-smoking alcohol dependent patients.

We hypothesize that mecamylamine will result in a greater reduction of alcohol consumption than placebo. We further hypothesize that mecamylamine will be effective in reducing both alcohol consumption and smoking in a subset of alcoholics who also smoke.

Detailed Description: RESEARCH PLAN: Although there are two FDA approved medications for the treatment of alcohol dependence (naltrexone and disulfiram), the robust efficacy of both compounds in reducing alcohol consumption has recently been called into question. Given the high rates of alcohol dependence among the general population, development and testing of novel medications is of great importance.

Mecamylamine, a noncompetitive NACh receptor antagonist has been shown to be useful in smoking cessation when used in combination with transdermal nicotine. To our knowledge, clinical studies examining the effectiveness of mecamylamine in alcoholism have not been conducted. However, there is evidence from animal research that mecamylamine can block the effects of alcohol. Infusion of mecamylamine into the ventral tegmental area antagonized ethanol-induced dopamine release in rats. More importantly, mecamylamine decreased alcohol intake and preference in alcohol-preferring rats. In two studies with healthy volunteers mecamylamine was effective in attenuating the euphoric effects of alcohol and reducing the craving for alcohol.

This is the first study designed to test the clinical efficacy of mecamylamine in a sample of alcohol dependent patients who either do or do not smoke.

For the proposed project we will recruit 60 treatment seeking patients between the ages of 18 and 60 who meet criteria for alcohol dependence and may or may not smoke. Patients will be randomized into two groups (30 patients in each group): one dose of mecamylamine (10mg) or placebo in a double-blind fashion for 12 weeks. Patients will be asked to come for follow up 3 months after completing the study. Patients will be excluded if they: take medications thought to influence drinking behavior, have a significant underlying medical conditions, such as cerebral, renal, thyroid, hepatic or cardiac pathology; have a history of glaucoma, prostatic hypertrophy, urethral obstruction, cerebral arteriosclerosis, pyloric stenosis, or a history of hypersensitivity to mecamylamine; or meet current criteria for Bipolar Disorders, Schizophrenia and Schizophrenia-type Disorders, Major Depression or Posttraumatic Stress Disorders (PTSD). Females who are pregnant or lactating will also be excluded.

We hypothesize that mecamylamine will result in a greater reduction of alcohol consumption than placebo among the alcohol dependent patients. We further hypothesize that mecamylamine will be effective in reducing both alcohol consumption and smoking in a subgroup of alcoholics who also smoke.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 136

Inclusion Criteria

individuals with DSM-IV diagnosis of alcohol dependence
smokers and non-smokers
patients who do not require psychotropic medication for the management of their psychiatric symptoms
individuals with a history of substance dependence (other than alcohol and tobacco) but have not met criteria for substance dependence in the past 30 days
women with acceptable method of contraception

Exclusion Criteria

pregnant women
medications thought to influence drinking behavior including: acamprosate, disulfiram, naltrexone and ondansetron
underlying medical conditions
history of glaucoma, prostatic hypertrophy, urethral obstruction, cerebral arteriosclerosis, pyloric stenosis, or a history of hypersensitivity to mecamylamine
DSM-IV diagnosis of bipolar disorder, schizophrenia, and schizophrenia-type disorders
unstable medical conditions
patients who require psychotropic medication for the management of an active psychiatric disorder
patients on pharmacological treatment for alcohol and/or nicotine dependence

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mecamylamine- Smoker	mecamylamine	-
Placebo-Smoker	Placebo	-
Mecamylamine- Non-Smoker	mecamylamine	-
Placebo-Non-Smoker	Placebo	-

Primary Outcome Measures

Name	Time	Method
Percent Heavy Drinking Days During Active Treatment Phase	12 weeks	Data were calculated as number of heavy drinking days (heavy drinking days is defined as 5 drinks on a single occasion for men and 4 for women) average during 90 days of treatment.
Self-report Weekly Craving Via Obsessive Compulsive Drinking Scale (OCDS)	12 weeks	The OCDS is a 14-item (rated 0-4), self-administered questionnaire for characterizing and quantifying the obsessive and compulsive cognitive aspects of craving and heavy (alcoholic) drinking, such as drinking-related thought, urges to drink, and the ability to resist those thoughts and urges. A higher total score indicates higher craving and ranges from 0-48.
Self-report Weekly Smoking Craving	12 weeks	Questionnaire of smoking urges (QSU). It has 32 questions that range from 1 to 7, there are 8 questions per sub-scale. The total range is 32 to 224. Each sub-scale ranges from 8- 56, with a higher score indicating higher craving.
Self-report Average Number of Cigarettes Per Day	12 weeks	self-report from only the smoking population for cigarettes per day