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Mecamylamine for the Treatment of Patients With Depression and Alcohol Dependence

Primary Purpose

Alcohol Dependence, Depression

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Mecamylamine
Placebo
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alcohol Dependence focused on measuring treatment, alcohol dependence, depression, mecamylamine

Eligibility Criteria

21 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Individuals with the DSM-IV diagnosis of Major Depression (MD) and Alcohol Dependence (AD) (using the SCID).
  2. Individuals who have been on a stable SSRI dose for 2 weeks.
  3. Smokers and non-smokers (smokers are defined as smoking more than 5 cigarettes per day).
  4. Individuals who have a history of substance dependence (other than alcohol, tobacco and cocaine) but have not met criteria for substance dependence in the past 30 days will be included (using the SCID).
  5. Women of childbearing potential must have a negative pregnancy test and use an acceptable method of contraception.
  6. Individuals who are able to participate psychologically and physically; give informed consent; complete the assessments; take the study medication; and otherwise participate in the trial. A post-consent test will be given to assess patient's capacity to give informed consent.

Exclusion Criteria:

  1. Females who are pregnant or lactating.
  2. Patients may not be taking medications thought to influence drinking behavior, including: acamprosate, disulfiram, naltrexone, or ondansetron.
  3. Patients with significant underlying medical conditions, such as cerebral, renal, thyroid, hepatic or cardiac pathology, which in the opinion of the physician would preclude the patient from fully cooperating or be of potential harm during the course of the study.
  4. Patients with a history of glaucoma, prostatic hypertrophy, urethral obstruction, cerebral arteriosclerosis, pyloric stenosis, or a history of hypersensitivity to mecamylamine.
  5. Patients who meet current SCID criteria for the following major Axis I diagnosis (Posttraumatic Stress Disorders (PTSD), Bipolar Disorders, Schizophrenia and Schizophrenia-type Disorders).
  6. Patients with a current unstable medical condition such as neurological, cardiovascular, endocrine, renal, liver, or thyroid pathology (LFT more than 5 times normal, abnormal BUN and creatinine, and unmanaged hypertension with BP higher than 200/120).
  7. Patients on pharmacological treatments for alcohol and/or nicotine dependence. (8) Patients taking bethanechol. (9) Patients at risk for suicide.

Sites / Locations

  • VA Connecticut Healthcare System

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Mecamylamine

Placebo

Arm Description

Mecamylamine is a noncompetitive, high-affinity nAChR antagonist with low selectivity for the alpha-7 receptor. Those receiving mecamylamine started at 2.5mg once daily (second dose was placebo). The dose was increased to 5.0 mg twice daily over 3 weeks.

Placebo capsules were prepared by the pharmacy and were identical in size and color to the medication capsules.

Outcomes

Primary Outcome Measures

Number of Drinking Days
Measured with time line follow back measures
Depression - Measured Using the HAMD Total Score
The Hamilton Depression Rating Scale (HAM-D) has proven useful for many years as a way of determining a patient's level of depression before, during, and after treatment. It should be administered by a clinician experienced in working with psychiatric patients. Although the HAM-D form lists 21 items, the scoring is based on the first 17. It generally takes 15-20 minutes to complete the interview and score the results. The Scale ranges from 0 (normal) to >23 (Very Severe Depression)

Secondary Outcome Measures

Mean Percentage of Number of Drinking Days by Smoking Status
Two-way interaction between smoking and medication for percentage of drinking days captured by time line follow back surveys. Data are calculated as number of drinking days over the number of days in the study for smokers and nonsmokers receiving either mecamylamine or placebo.
Mean Percentage of Heavy Drinking Days by Smoking
The two-way interaction between medication by smoking status to measure percentage of heavy drinking days measured by time line follow back survey. 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) over the number of days in the study for smokers and non smokers receiving either mecamylamine or placebo.

Full Information

First Posted
November 21, 2007
Last Updated
March 21, 2016
Sponsor
Yale University
Collaborators
National Alliance for Research on Schizophrenia and Depression
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1. Study Identification

Unique Protocol Identification Number
NCT00563797
Brief Title
Mecamylamine for the Treatment of Patients With Depression and Alcohol Dependence
Official Title
Mecamylamine for the Treatment of Patients With Depression and Alcohol Dependence
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
August 2007 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
July 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
Collaborators
National Alliance for Research on Schizophrenia and Depression

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The objective of this study is to evaluate the efficacy of mecamylamine (MEC, 10 mg/day) versus placebo in reducing depressive and alcohol symptoms in patients with depression and co-morbid alcohol dependence. The researchers hypothesize that MEC will significantly reduce depressive symptoms and decrease alcohol consumption compared to placebo in patients with depression and alcohol dependence who are on a stable dose of a selective serotonin reuptake inhibitor (SSRI).
Detailed Description
Depression with co-morbid alcohol dependence is very prevalent and it is very costly to treat. The co occurrence of the two disorders leads to greater severity and worse long-term outcome, including suicide. Although a number of treatment strategies have been implemented for depressed patients with alcohol dependence the controversy concerning best treatment options for those patients persists. The clinical relationship between depression and alcohol dependence suggests some common mechanism underlying both disorders. It has been hypothesized that medications that block presynaptic nAChR may be effective in the treatment of alcoholism and depression. Mecamylamine (Inversine ®) is a noncompetitive, high affinity nAChR antagonist with low selectivity for the alpha-7 receptor. Mecamylamine has never been investigated as an effective adjunct treatment for dually diagnosed patients with depression and alcohol dependence. Methods: Thirty participants with a current diagnosis of depression and alcohol dependence will be recruited for this 12-week treatment study. Fifteen participants will be randomized to mecamylamine and fifteen to placebo. Participants will be included in the study if: they meet current DSM-IV criteria for Major Depression and Alcohol Dependence and have been on a stable SSRI dose for 2 weeks. All participants will come weekly to take their medications and complete weekly assessments. Weekly assessments will consist of questioners that will assess depressive symptoms and alcohol consumption over the entire treatment period. Significance: This study is the first to evaluate the efficacy of mecamylamine as an augmenting agent for treatment of depression and alcohol dependence.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Dependence, Depression
Keywords
treatment, alcohol dependence, depression, mecamylamine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Mecamylamine
Arm Type
Experimental
Arm Description
Mecamylamine is a noncompetitive, high-affinity nAChR antagonist with low selectivity for the alpha-7 receptor. Those receiving mecamylamine started at 2.5mg once daily (second dose was placebo). The dose was increased to 5.0 mg twice daily over 3 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo capsules were prepared by the pharmacy and were identical in size and color to the medication capsules.
Intervention Type
Drug
Intervention Name(s)
Mecamylamine
Intervention Description
mecamylamine 10mg/day for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo pill
Primary Outcome Measure Information:
Title
Number of Drinking Days
Description
Measured with time line follow back measures
Time Frame
25 weeks
Title
Depression - Measured Using the HAMD Total Score
Description
The Hamilton Depression Rating Scale (HAM-D) has proven useful for many years as a way of determining a patient's level of depression before, during, and after treatment. It should be administered by a clinician experienced in working with psychiatric patients. Although the HAM-D form lists 21 items, the scoring is based on the first 17. It generally takes 15-20 minutes to complete the interview and score the results. The Scale ranges from 0 (normal) to >23 (Very Severe Depression)
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Mean Percentage of Number of Drinking Days by Smoking Status
Description
Two-way interaction between smoking and medication for percentage of drinking days captured by time line follow back surveys. Data are calculated as number of drinking days over the number of days in the study for smokers and nonsmokers receiving either mecamylamine or placebo.
Time Frame
25 weeks
Title
Mean Percentage of Heavy Drinking Days by Smoking
Description
The two-way interaction between medication by smoking status to measure percentage of heavy drinking days measured by time line follow back survey. 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) over the number of days in the study for smokers and non smokers receiving either mecamylamine or placebo.
Time Frame
25 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Individuals with the DSM-IV diagnosis of Major Depression (MD) and Alcohol Dependence (AD) (using the SCID). Individuals who have been on a stable SSRI dose for 2 weeks. Smokers and non-smokers (smokers are defined as smoking more than 5 cigarettes per day). Individuals who have a history of substance dependence (other than alcohol, tobacco and cocaine) but have not met criteria for substance dependence in the past 30 days will be included (using the SCID). Women of childbearing potential must have a negative pregnancy test and use an acceptable method of contraception. Individuals who are able to participate psychologically and physically; give informed consent; complete the assessments; take the study medication; and otherwise participate in the trial. A post-consent test will be given to assess patient's capacity to give informed consent. Exclusion Criteria: Females who are pregnant or lactating. Patients may not be taking medications thought to influence drinking behavior, including: acamprosate, disulfiram, naltrexone, or ondansetron. Patients with significant underlying medical conditions, such as cerebral, renal, thyroid, hepatic or cardiac pathology, which in the opinion of the physician would preclude the patient from fully cooperating or be of potential harm during the course of the study. Patients with a history of glaucoma, prostatic hypertrophy, urethral obstruction, cerebral arteriosclerosis, pyloric stenosis, or a history of hypersensitivity to mecamylamine. Patients who meet current SCID criteria for the following major Axis I diagnosis (Posttraumatic Stress Disorders (PTSD), Bipolar Disorders, Schizophrenia and Schizophrenia-type Disorders). Patients with a current unstable medical condition such as neurological, cardiovascular, endocrine, renal, liver, or thyroid pathology (LFT more than 5 times normal, abnormal BUN and creatinine, and unmanaged hypertension with BP higher than 200/120). Patients on pharmacological treatments for alcohol and/or nicotine dependence. (8) Patients taking bethanechol. (9) Patients at risk for suicide.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elizabeth Ralevski, Ph.D.
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Connecticut Healthcare System
City
West Haven
State/Province
Connecticut
ZIP/Postal Code
06516
Country
United States

12. IPD Sharing Statement

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