Prometa Protocol for Alcohol Dependence

February 8, 2019 updated by: Raymond F. Anton, Medical University of South Carolina

A Double Blind Evaluation of Flumazenil and Gabapentin for the Treatment of Alcohol Withdrawal and Relapse Prevention

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 2
  • Phase 3

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
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • MUSC-Center for Drug and Alcohol Programs

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 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age 18 - 70.
  2. 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.
  3. No more than 72 hours since last drink of alcohol. Rationale: to focus on symptoms occurring during the early alcohol cessation period.
  4. 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.
  5. Able to read and understand questionnaires and informed consent.
  6. Has stable housing for past 3 months.

Exclusion Criteria:

  1. Currently meets DSM-IV criteria for any other psychoactive substance dependence disorder except nicotine dependence.
  2. Any psychoactive substance abuse, except marijuana and nicotine, within the last 30 days as evidenced by subject report or urine drug screen.
  3. 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.
  4. No use of benzodiazepines in excess of three times in the past two weeks by self report and urine drug screen.
  5. Subjects must not be taking zolpidem (Ambien™), zaleplon (Sonata™), or eszopiclone (Lunesta™) in excess of three times in past two weeks.
  6. No history of delirium tremens or alcohol withdrawal seizures.
  7. Has current suicidal ideation with plan or homicidal ideation.
  8. Need for maintenance or acute treatment with any psychoactive medication including antiseizure medications.
  9. Use of disulfiram, naltrexone, acamprosate, or anticonvulsants in last 30 days.
  10. Clinically significant medical problems such as cardiovascular, renal, GI, or endocrine problem that would impair participation or limit medication ingestion.
  11. 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.
  12. Has current charges pending for a violent crime (not including DUI related offenses).
  13. Has taken gabapentin or flumazenil in the last month or has experienced adverse effects from it at any time in the past.
  14. Hepatocellular disease indicated by elevations of SGPT (ALT) and SGOT (AST) greater than 3 times normal at screening.
  15. Persons with metal implants or pacemaker since fMRI will be used.

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: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: I
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.
Drug: Flumazenil and Gabapentin
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.
Placebo Comparator: II
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.
Drug: Flumazenil and Gabapentin
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.
Drug: Placebo
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Subjects Completely Abstinent
Time Frame: 6 week trial
percent of subjects completely abstinent during the six week medication study study
6 week trial
Percent Days Abstinent
Time Frame: Weeks 1 to 6
percent days abstinent during treatment
Weeks 1 to 6

Collaborators and Investigators

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

Sponsor

Medical University of South Carolina

Investigators

  • Principal Investigator: Raymond F Anton, MD, Medical University of South Carolina

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

Helpful Links

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

December 1, 2005

Primary Completion (Actual)

February 1, 2008

Study Completion (Actual)

March 1, 2008

Study Registration Dates

First Submitted

December 5, 2005

First Submitted That Met QC Criteria

December 5, 2005

First Posted (Estimate)

December 7, 2005

Study Record Updates

Last Update Posted (Actual)

February 15, 2019

Last Update Submitted That Met QC Criteria

February 8, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15844

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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