Clinical trial NCT00342563: Treatment With Mecamylamine in Smoking and Non-smoking Alcohol Dependent Patients
Official title: Treatment With Mecamylamine in Smoking and Non-smoking Alcohol Dependent Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alcoholism
Keywords: mecamylamine
treatment
alcohol dependence
smoking
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2006-06-21
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percent Heavy Drinking Days During Active Treatment Phase
timeFrame: 12 weeks
measure: Self-report Weekly Craving Via Obsessive Compulsive Drinking Scale (OCDS)
timeFrame: 12 weeks
measure: Self-report Weekly Smoking Craving
timeFrame: 12 weeks
measure: Self-report Average Number of Cigarettes Per Day
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: West Haven
country: United States
facility: VA Connecticut Healthcare System
state: Connecticut
Study officials:
affiliation: Yale University
name: Ismene Petrakis, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gandelman E, Petrakis I, Kachadourian L, Ralevski E. Negative Affect Intensity and Hostility in Individuals With Alcohol Use Disorder With or Without Posttraumatic Stress Disorder. J Dual Diagn. 2018 Apr-Jun;14(2):96-101. doi: 10.1080/15504263.2018.1434264. Epub 2018 Apr 25.