Alcoholism
Conditions
Keywords
mecamylamine, treatment, alcohol dependence, smoking
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.
Interventions
DRUGmecamylamine
mecamylamine 10mg/day
DRUGPlacebo
Placebo
Sponsors
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mecamylamine-Smoker mecamylamine: mecamylamine 10mg/day | 41 |
| Mecamylamine-Non-Smoker | 27 |
| Placebo-Smoker Placebo: Placebo | 40 |
| Placebo- Non-Smoker | 28 |
| Total | 136 |
Baseline characteristics
| Characteristic | Mecamylamine-Smoker | Mecamylamine-Non-Smoker | Placebo-Smoker | Placebo- Non-Smoker | Total |
|---|---|---|---|---|---|
| Age, Continuous | 45.83 years STANDARD_DEVIATION 8.42 | 50.93 years STANDARD_DEVIATION 9.55 | 47.28 years STANDARD_DEVIATION 8.69 | 51.14 years STANDARD_DEVIATION 10.28 | 48.4 years STANDARD_DEVIATION 9.3 |
| Race/Ethnicity, Customized Black | 17 participants | 14 participants | 18 participants | 18 participants | 67 participants |
| Race/Ethnicity, Customized Other | 1 participants | 0 participants | 1 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized White | 23 participants | 13 participants | 21 participants | 10 participants | 67 participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 6 Participants | 4 Participants | 20 Participants |
| Sex: Female, Male Male | 35 Participants | 23 Participants | 34 Participants | 24 Participants | 116 Participants |
| Veteran Status Non-Veteran | 22 participants | 18 participants | 22 participants | 20 participants | 82 participants |
| Veteran Status Veteran | 19 participants | 9 participants | 18 participants | 8 participants | 54 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 0 / 27 | 0 / 40 | 0 / 28 |
| other Total, other adverse events | 41 / 41 | 27 / 27 | 40 / 40 | 28 / 28 |
| serious Total, serious adverse events | 3 / 41 | 0 / 27 | 1 / 40 | 1 / 28 |
Outcome results
Primary
Percent Heavy Drinking Days During Active Treatment Phase
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.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mecamylamine- Smokers | Percent Heavy Drinking Days During Active Treatment Phase | 16.75 days | Standard Error 4.33 |
| Mecamylamine- Non-Smoker | Percent Heavy Drinking Days During Active Treatment Phase | 24.28 days | Standard Error 5.3 |
| Placebo-Smoker | Percent Heavy Drinking Days During Active Treatment Phase | 20.51 days | Standard Error 4.57 |
| Placebo- Non-Smoker | Percent Heavy Drinking Days During Active Treatment Phase | 21.78 days | Standard Error 5.11 |
Primary
Self-report Average Number of Cigarettes Per Day
self-report from only the smoking population for cigarettes per day
Time frame: 12 weeks
Population: only smokers
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mecamylamine- Smokers | Self-report Average Number of Cigarettes Per Day | 8.055 cigarettes | Standard Error 1.163 |
| Mecamylamine- Non-Smoker | Self-report Average Number of Cigarettes Per Day | 10.681 cigarettes | Standard Error 1.258 |
Primary
Self-report Weekly Craving Via Obsessive Compulsive Drinking Scale (OCDS)
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.
Time frame: 12 weeks
Population: Scores presented are total, and then by subgroup.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mecamylamine- Smokers | Self-report Weekly Craving Via Obsessive Compulsive Drinking Scale (OCDS) | Total | 8.772 units on a scale | Standard Error 1.165 |
| Mecamylamine- Smokers | Self-report Weekly Craving Via Obsessive Compulsive Drinking Scale (OCDS) | Non-Smokers | 10.575 units on a scale | Standard Error 1.851 |
| Mecamylamine- Smokers | Self-report Weekly Craving Via Obsessive Compulsive Drinking Scale (OCDS) | Smokers | 6.969 units on a scale | Standard Error 1.713 |
| Mecamylamine- Non-Smoker | Self-report Weekly Craving Via Obsessive Compulsive Drinking Scale (OCDS) | Total | 8.032 units on a scale | Standard Error 1.146 |
| Mecamylamine- Non-Smoker | Self-report Weekly Craving Via Obsessive Compulsive Drinking Scale (OCDS) | Non-Smokers | 8.352 units on a scale | Standard Error 1.676 |
| Mecamylamine- Non-Smoker | Self-report Weekly Craving Via Obsessive Compulsive Drinking Scale (OCDS) | Smokers | 7.712 units on a scale | Standard Error 1.563 |
Primary
Self-report Weekly Smoking Craving
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.
Time frame: 12 weeks
Population: Smokers only
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mecamylamine- Smokers | Self-report Weekly Smoking Craving | Desire to Smoke | 27.741 units on a scale | Standard Error 1.311 |
| Mecamylamine- Smokers | Self-report Weekly Smoking Craving | Anticipation of a positive outcome | 28.705 units on a scale | Standard Error 1.718 |
| Mecamylamine- Smokers | Self-report Weekly Smoking Craving | Relief | 22.557 units on a scale | Standard Error 1.604 |
| Mecamylamine- Smokers | Self-report Weekly Smoking Craving | Intention to smoke | 31.108 units on a scale | Standard Error 1.793 |
| Mecamylamine- Non-Smoker | Self-report Weekly Smoking Craving | Intention to smoke | 32.549 units on a scale | Standard Error 1.946 |
| Mecamylamine- Non-Smoker | Self-report Weekly Smoking Craving | Desire to Smoke | 28.047 units on a scale | Standard Error 1.442 |
| Mecamylamine- Non-Smoker | Self-report Weekly Smoking Craving | Relief | 24.032 units on a scale | Standard Error 1.73 |
| Mecamylamine- Non-Smoker | Self-report Weekly Smoking Craving | Anticipation of a positive outcome | 28.273 units on a scale | Standard Error 1.857 |