NCT00262639

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Dec 2005

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2005

Completed
4 days until next milestone

First Submitted

Initial submission to the registry

December 5, 2005

Completed
2 days until next milestone

First Posted

Study publicly available on registry

December 7, 2005

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2008

Completed
29 days until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2008

Completed
1.5 years until next milestone

Results Posted

Study results publicly available

August 14, 2009

Completed
Last Updated

February 15, 2019

Status Verified

February 1, 2019

Enrollment Period

2.2 years

First QC Date

December 5, 2005

Results QC Date

July 6, 2009

Last Update Submit

February 8, 2019

Conditions

Keywords

AlcoholismAlcohol DependenceAlcohol WithdrawalTreatmentPharmacotherapy

Outcome Measures

Primary Outcomes (2)

  • Percent Subjects Completely Abstinent

    percent of subjects completely abstinent during the six week medication study study

    6 week trial

  • Percent Days Abstinent

    percent days abstinent during treatment

    Weeks 1 to 6

Study Arms (2)

I

EXPERIMENTAL

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

II

PLACEBO COMPARATOR

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 GabapentinDrug: Placebo

Interventions

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.

III

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.

II

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

MUSC-Center for Drug and Alcohol Programs

Charleston, South Carolina, 29425, United States

Location

Related Publications (2)

  • 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.

  • 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.

Related Links

MeSH Terms

Conditions

Alcoholism

Interventions

FlumazenilGabapentin

Condition Hierarchy (Ancestors)

Alcohol-Related DisordersSubstance-Related DisordersChemically-Induced DisordersMental Disorders

Intervention Hierarchy (Ancestors)

BenzodiazepinonesBenzodiazepinesBenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsAminesOrganic Chemicalsgamma-Aminobutyric AcidAminobutyratesButyratesAcids, AcyclicCarboxylic AcidsCyclohexanecarboxylic AcidsAcids, CarbocyclicCyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsAmino AcidsAmino Acids, Peptides, and Proteins

Results Point of Contact

Title
Raymond F. Anton, M.D.
Organization
Medical University of South Carolina

Study Officials

  • Raymond F Anton, MD

    Medical University of South Carolina

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Distinguished University Professor

Study Record Dates

First Submitted

December 5, 2005

First Posted

December 7, 2005

Study Start

December 1, 2005

Primary Completion

February 1, 2008

Study Completion

March 1, 2008

Last Updated

February 15, 2019

Results First Posted

August 14, 2009

Record last verified: 2019-02

Locations