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

May 24, 2019 updated by: Yale University

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

136

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • West Haven, Connecticut, United States, 06516
        • VA Connecticut Healthcare System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Mecamylamine- Smoker
Drug: mecamylamine
mecamylamine 10mg/day
Placebo Comparator: Placebo-Smoker
Drug: Placebo
Placebo
Experimental: Mecamylamine- Non-Smoker
Drug: mecamylamine
mecamylamine 10mg/day
Placebo Comparator: Placebo-Non-Smoker
Drug: Placebo
Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Heavy Drinking Days During Active Treatment Phase
Time Frame: 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.
12 weeks
Self-report Weekly Craving Via Obsessive Compulsive Drinking Scale (OCDS)
Time Frame: 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.
12 weeks
Self-report Weekly Smoking Craving
Time Frame: 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.
12 weeks
Self-report Average Number of Cigarettes Per Day
Time Frame: 12 weeks
self-report from only the smoking population for cigarettes per day
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yale University

Investigators

  • Principal Investigator: Ismene Petrakis, M.D., Yale University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2004

Primary Completion (Actual)

July 1, 2015

Study Completion (Actual)

July 1, 2015

Study Registration Dates

First Submitted

June 19, 2006

First Submitted That Met QC Criteria

June 19, 2006

First Posted (Estimate)

June 21, 2006

Study Record Updates

Last Update Posted (Actual)

June 4, 2019

Last Update Submitted That Met QC Criteria

May 24, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 26364

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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