search
Back to results

Prometa Protocol for Alcohol Dependence

Primary Purpose

Alcohol Dependence

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Flumazenil and Gabapentin
Placebo
Sponsored by
Medical University of South Carolina
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alcohol Dependence focused on measuring Alcoholism, Alcohol Dependence, Alcohol Withdrawal, Treatment, Pharmacotherapy

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age 18 - 70. Participants will meet criteria for primary DSM IV alcohol dependence, drink on at least 70% of days in the last 30 days prior to assessment, and drink at least 5 drinks per drinking day. No more than 72 hours since last drink of alcohol. Rationale: to focus on symptoms occurring during the early alcohol cessation period. Low CIWA-Ar group: have a CIWA-Ar score less than or equal to 6; High CIWA-Ar group: have a CIWA-Ar score greater than or equal to 7 but less than or equal to 15. Able to read and understand questionnaires and informed consent. Has stable housing for past 3 months. Exclusion Criteria: Currently meets DSM-IV criteria for any other psychoactive substance dependence disorder except nicotine dependence. Any psychoactive substance abuse, except marijuana and nicotine, within the last 30 days as evidenced by subject report or urine drug screen. Meets DSM-IV criteria for current axis I disorders of major depression, panic disorder, obsessive-compulsive disorder, generalized anxiety disorder, post-traumatic stress syndrome, bipolar affective disorder, schizophrenia, or any other psychotic disorder or organic mental disorder. The rationale for excluding them is that symptoms from these disorders may affect dependent variables and complicate interpretation of the data. No use of benzodiazepines in excess of three times in the past two weeks by self report and urine drug screen. Subjects must not be taking zolpidem (Ambien™), zaleplon (Sonata™), or eszopiclone (Lunesta™) in excess of three times in past two weeks. No history of delirium tremens or alcohol withdrawal seizures. Has current suicidal ideation with plan or homicidal ideation. Need for maintenance or acute treatment with any psychoactive medication including antiseizure medications. Use of disulfiram, naltrexone, acamprosate, or anticonvulsants in last 30 days. Clinically significant medical problems such as cardiovascular, renal, GI, or endocrine problem that would impair participation or limit medication ingestion. Sexually active females of child-bearing potential who are pregnant (by -beta HCG), nursing, or who are not using a reliable form of birth control. Has current charges pending for a violent crime (not including DUI related offenses). Has taken gabapentin or flumazenil in the last month or has experienced adverse effects from it at any time in the past. Hepatocellular disease indicated by elevations of SGPT (ALT) and SGOT (AST) greater than 3 times normal at screening. Persons with metal implants or pacemaker since fMRI will be used.

Sites / Locations

  • MUSC-Center for Drug and Alcohol Programs

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

I

II

Arm Description

2 mg flumazenil given over 20 minutes on Day 1 and Day 2. Gabapentin 300 mg Day 1; gabapentin 600 mg Day 2; gabapentin 900 mg Day 3; gabapentin 1200 mg Day 4 to 30; gabapentin 900 mg day 31-33; gabapentin 600 mg day 34-36; gabapentin 300 mg day 37-39.

20 mg Saline infused slowly over 20 minutes. Placebo 1 capsule Day 1, 2 capsules Day 2, 3 capsules Day 3, 4 capsules days 4 to 30; 3 capsules Day 31 to 33; 2 capsules day 34 to 36 and 1 capsule 37 to 39.

Outcomes

Primary Outcome Measures

Percent Subjects Completely Abstinent
percent of subjects completely abstinent during the six week medication study study
Percent Days Abstinent
percent days abstinent during treatment

Secondary Outcome Measures

Full Information

First Posted
December 5, 2005
Last Updated
February 8, 2019
Sponsor
Medical University of South Carolina
search

1. Study Identification

Unique Protocol Identification Number
NCT00262639
Brief Title
Prometa Protocol for Alcohol Dependence
Official Title
A Double Blind Evaluation of Flumazenil and Gabapentin for the Treatment of Alcohol Withdrawal and Relapse Prevention
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
December 2005 (undefined)
Primary Completion Date
February 2008 (Actual)
Study Completion Date
March 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of South Carolina

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a placebo controlled trial (some people receive active and some people receive inactive medication) to evaluate the effectiveness of a new protocol to treat alcohol dependence. Two main medications (plus ancillary non-placebo controlled medications) and their placebos (inactive drugs) will be utilized to treat both alcohol withdrawal, promote abstinence, and reduce drinking over approximately a six-week treatment period. All participants will meet criteria for Alcohol Dependence and be drinking heavily up until 72 hours prior to receiving the first study drug. They will be injected one drug (flumazenil or placebo) over a two day period and receive the second one (gabapentin or placebo) by mouth for 39 days. The main hypothesis is that this protocol will reduce early alcohol withdrawal symptoms and will reduce relapse to drinking and promote abstinence compared to the placebo (inactive) drug group. Secondary outcomes that will be evaluated include reduction in craving, improvement in sleep, brain activity and mood.
Detailed Description
Approximately 60 alcohol dependent individuals who are drinking heavily up until 72 hours, or less, prior to study participation will be randomized to receive either flumazenil (intravenously)on two successive days and gabapentin (orally)for 39 days or their matching placebos. They also will receive hydroxyzine and vitamins. Individuals will be evaluated for alcohol withdrawal, their response to acoustic startle, cognitive ability, craving, mood, sleep and drinking during the first week. They will then be seen weekly for about 6 weeks during which they take gabapentin or placebo and are provided with Combined Behavioral Intervention Therapy (counseling) once a week, or more, as required. Over this period they will be evaluated weekly for alcohol consumption, craving, sleep, mood, and biological markers of alcohol consumption ( percent carbohydrate deficient transferrin and gamma-glutamyl transferase). Blood will be obtained on week 3 and 6 for general health (liver, blood count etc.) screening. After the end of treatment, subjects will be followed-up at 4 weeks and again at 8 weeks after treatment to evaluate alcohol consumption, craving, sleep, mood. Subjects will undergo a functional magnetic resonance imaging (MRI) procedure sometime during the second or third week of study medication to assess cue induced regional brain activation to investigate the effect of medication on brain response to alcohol visual cues.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Dependence
Keywords
Alcoholism, Alcohol Dependence, Alcohol Withdrawal, Treatment, Pharmacotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
I
Arm Type
Experimental
Arm Description
2 mg flumazenil given over 20 minutes on Day 1 and Day 2. Gabapentin 300 mg Day 1; gabapentin 600 mg Day 2; gabapentin 900 mg Day 3; gabapentin 1200 mg Day 4 to 30; gabapentin 900 mg day 31-33; gabapentin 600 mg day 34-36; gabapentin 300 mg day 37-39.
Arm Title
II
Arm Type
Placebo Comparator
Arm Description
20 mg Saline infused slowly over 20 minutes. Placebo 1 capsule Day 1, 2 capsules Day 2, 3 capsules Day 3, 4 capsules days 4 to 30; 3 capsules Day 31 to 33; 2 capsules day 34 to 36 and 1 capsule 37 to 39.
Intervention Type
Drug
Intervention Name(s)
Flumazenil and Gabapentin
Intervention Description
2 mg flumazenil for infusion given slowly over 20 minutes given day 1 and day 2 gabapentin 300 mg increasing to 1200 mg over 4 days and continuing to day 30. Gabapentin 900 mg Day 31 to Day 33 gabapentin 600 mg Day 34 to 36 and gabapentin 300 mg Day 37 to 39.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
20 mg Saline infused slowly over 20 minutes. Placebo 1 capsule Day 1, 2 capsules Day 2, 3 capsules Day 3, 4 capsules days 4 to 30; 3 capsules Day 31 to 33; 2 capsules day 34 to 36 and 1 capsule 37 to 39.
Primary Outcome Measure Information:
Title
Percent Subjects Completely Abstinent
Description
percent of subjects completely abstinent during the six week medication study study
Time Frame
6 week trial
Title
Percent Days Abstinent
Description
percent days abstinent during treatment
Time Frame
Weeks 1 to 6

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18 - 70. Participants will meet criteria for primary DSM IV alcohol dependence, drink on at least 70% of days in the last 30 days prior to assessment, and drink at least 5 drinks per drinking day. No more than 72 hours since last drink of alcohol. Rationale: to focus on symptoms occurring during the early alcohol cessation period. Low CIWA-Ar group: have a CIWA-Ar score less than or equal to 6; High CIWA-Ar group: have a CIWA-Ar score greater than or equal to 7 but less than or equal to 15. Able to read and understand questionnaires and informed consent. Has stable housing for past 3 months. Exclusion Criteria: Currently meets DSM-IV criteria for any other psychoactive substance dependence disorder except nicotine dependence. Any psychoactive substance abuse, except marijuana and nicotine, within the last 30 days as evidenced by subject report or urine drug screen. Meets DSM-IV criteria for current axis I disorders of major depression, panic disorder, obsessive-compulsive disorder, generalized anxiety disorder, post-traumatic stress syndrome, bipolar affective disorder, schizophrenia, or any other psychotic disorder or organic mental disorder. The rationale for excluding them is that symptoms from these disorders may affect dependent variables and complicate interpretation of the data. No use of benzodiazepines in excess of three times in the past two weeks by self report and urine drug screen. Subjects must not be taking zolpidem (Ambien™), zaleplon (Sonata™), or eszopiclone (Lunesta™) in excess of three times in past two weeks. No history of delirium tremens or alcohol withdrawal seizures. Has current suicidal ideation with plan or homicidal ideation. Need for maintenance or acute treatment with any psychoactive medication including antiseizure medications. Use of disulfiram, naltrexone, acamprosate, or anticonvulsants in last 30 days. Clinically significant medical problems such as cardiovascular, renal, GI, or endocrine problem that would impair participation or limit medication ingestion. Sexually active females of child-bearing potential who are pregnant (by -beta HCG), nursing, or who are not using a reliable form of birth control. Has current charges pending for a violent crime (not including DUI related offenses). Has taken gabapentin or flumazenil in the last month or has experienced adverse effects from it at any time in the past. Hepatocellular disease indicated by elevations of SGPT (ALT) and SGOT (AST) greater than 3 times normal at screening. Persons with metal implants or pacemaker since fMRI will be used.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Raymond F Anton, MD
Organizational Affiliation
Medical University of South Carolina
Official's Role
Principal Investigator
Facility Information:
Facility Name
MUSC-Center for Drug and Alcohol Programs
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19593171
Citation
Anton RF, Myrick H, Baros AM, Latham PK, Randall PK, Wright TM, Stewart SH, Waid R, Malcolm R. Efficacy of a combination of flumazenil and gabapentin in the treatment of alcohol dependence: relationship to alcohol withdrawal symptoms. J Clin Psychopharmacol. 2009 Aug;29(4):334-42. doi: 10.1097/JCP.0b013e3181aba6a4.
Results Reference
result
PubMed Identifier
21631542
Citation
Schacht JP, Randall PK, Waid LR, Baros AM, Latham PK, Wright TM, Myrick H, Anton RF. Neurocognitive performance, alcohol withdrawal, and effects of a combination of flumazenil and gabapentin in alcohol dependence. Alcohol Clin Exp Res. 2011 Nov;35(11):2030-8. doi: 10.1111/j.1530-0277.2011.01554.x. Epub 2011 Jun 1.
Results Reference
result
Links:
URL
http://www.muschealth.com/cdap/
Description
Main Web Page for the MUSC-Center for Drug and Alcohol Programs

Learn more about this trial

Prometa Protocol for Alcohol Dependence

We'll reach out to this number within 24 hrs