Comparative Study of Gamma-hydroxy Butyrate Versus Oxazepam in the Treatment of Alcohol Withdrawal Syndrome (GATE I)

March 17, 2014 updated by: Giovanni Addolorato, Catholic University of the Sacred Heart

The Gamma Hydroxybutyric Acid in Alcohol-dependence Treatment Efficacy (GATE) I Trial: a Comparative Study Versus Oxazepam in the Treatment of Alcohol Withdrawal Syndrome

Benzodiazepines (BDZs) are the gold standard in the treatment of alcohol withdrawal syndrome (AWS). Gamma-Hydroxybutyric acid also known as sodium oxybate (SMO) has been tested as a treatment for AWS with encouraging results. Aim of this phase IV, multicenter randomized double-blind, double dummy study is to evaluate the efficacy of SMO in comparison to oxazepam in the treatment of alcohol withdrawal symptoms (AWS).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a phase IV, multicenter randomized (1:1), active drug-controlled study (double-blind, double dummy) with parallel groups evaluating the efficacy of SMO versus oxazepam in the treatment of AWS in alcohol-dependent patients.

A placebo-controlled design was considered but excluded, given that a gold standard treatment for AWS is available (i.e., BDZs).

Furthermore, considering that SMO and oxazepam have two different pharmaceutical formulation (suspension and tablets, respectively), a double-dummy design was adopted.

Thus, all subjects will receive both medications, tablets (oxazepam or placebo) and suspension (SMO or placebo), at the same time.

Study Type

Interventional

Enrollment (Actual)

127

Phase

  • Phase 4

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

  • Austria
    • AT
      • Wien, AT, Austria
        • University of Wien
  • Italy
    • BO
      • Bologna, BO, Italy
        • "G. Fontana" Centre for the Study and Multidisciplinary Treatment of Alcohol Addiction, Department of Clinical Medicine, University of Bologna
    • Rm
      • Rome, Rm, Italy, 00168
        • Catholic University of Rome

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

21 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • age range 21-75,
  • diagnosis of alcohol dependence according to DSM-IV criteria
  • the presence of AWS as assessed by Clinical Institute Withdrawal Assessment for Alcohol-revised (CIWA-Ar) scale, a scoring system for quantitative evaluation of physical symptoms of AWS.20 Only subjects with a CIWA-Ar score equal to or higher than 10 (defined as moderate or severe AWS requiring pharmacological treatment) were ultimately enrolled in the study.

Exclusion criteria:

  • ≤55 kg of body weight;
  • history of withdrawal fits within 24 hours pre-study;
  • history of epilepsy or epileptics seizures not properly controlled by established anti-epileptic treatment;
  • dependence from narcotics, BDZs or other drugs of abuse;
  • documented pre-existent hypersensitivity to SMO or to BDZs,
  • renal failure (blood creatinine >2•5 mg/dl and/or documented proteinuria >500 mg/die),
  • heart failure,
  • severe respiratory failure
  • hepatic encephalopathy stage II-IV;
  • psychiatric disorders requiring treatment with psychoactive medications before the start of the study;
  • treatment with clonidine, haloperidol, bromocriptine during the last 3 months prior to participation in the study;
  • participation to other clinical investigations in the previous month prior to recruitment;
  • females whose could not assure not to become pregnant during the 1 month period of treatment, and during the subsequent 3 weeks;
  • subjects without a stable social condition or homeless.

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: Sodium oxybate (SMO)

Patients randomized to the first arm of the study will receive:

  • SMO (sodium oxybate 175 mg/ml suspension): 10ml at 8.00 a.m., 10ml at 12.00 p.m., 10ml at 7.00 p.m. from day 1 to day 5, 5ml at 8.00 a.m., 5ml at 12.00 p.m., 5ml at 7.00 pm, on days 6 and 7, and 2.5ml at 8.00 a.m., 2.5 ml at 12.00 p.m., 2.5ml at 7.00 p.m. from day 8 to day 10 (If patient's weight is > 75 kg the dosage will be of 12ml instead of 10 ml, 6ml instead of 5ml, 3 ml instead of 2.5ml);
  • placebo (tablets): 1 tablet at 8.00 a.m., 1 tablet at 12.00 p.m., 1 tablet at 7.00 p.m. from day 1 to day 10.
Drug: Sodium Oxybate (SMO)
Other Names:
  • Gamma-hydroxy butyrate (GHB)
Active Comparator: Oxazepam

Patients randomized to the second arm of the study will receive:

  • OXAZEPAM (tablets): 60mg at 8.00 a.m., 60mg at 12.00 p.m., 90mg at 7.00 p.m. from day 1 to day 5, 30mg at 8.00 a.m., 30mg at 12.00 p.m., 30mg at 7.00 pm, on days 6 and 7, and 15mg at 8.00 a.m., 15mg at 12.00 p.m., 15mg at 7.00 p.m. from day 8 to day 10;
  • placebo (suspension): 10ml at 8.00 a.m., 10ml at 12.00 p.m., 10ml at 7.00 p.m. from day 1 to day 5, 5ml at 8.00 a.m., 5ml at 12.00 p.m., 5ml at 7.00 pm, on days 6 and 7, and 2.5ml at 8.00 a.m., 2.5 ml at 12.00 p.m., 2.5ml at 7.00 p.m. from day 8 to day 10, (If patient's weight is > 75 kg the dosage will be of 12ml instead of 10 ml, 6ml instead of 5ml, 3 ml instead of 2.5ml).
Drug: Oxazepam

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of GHB compared to oxazepam on alcohol withdrawal symptoms
Time Frame: day 1, day 10, day 20
The primary outcome was the reduction of symptoms of AWS reflected by the course of the total CIWA-Ar scores from the start (baseline) to the end of the study (day 10) and to the end of follow up (day 20, 10 days after drugs discontinuation).
day 1, day 10, day 20

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Course of alcohol abstinence
Time Frame: day 1, day 10, day 20
Secondary outcome variables included the course of alcohol abstinence. In order to confirm daily alcohol abstinence, a breath analyzer was used. In addition, to define those subjects remaining abstinent throughout the whole treatment period, carbohydrate-deficient transferrin (%CDT) was evaluated at the time of screening and at the end of the treatment period.
day 1, day 10, day 20

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Craving for study drug.
Time Frame: day 1, day 10, day 20
Assessment of craving for the study drug.
day 1, day 10, day 20

Collaborators and Investigators

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

Sponsor

Catholic University of the Sacred Heart

Collaborators

Medical University of Vienna
University of Bologna
CT Pharmaceutical Industries, Sanremo - Italy

Investigators

  • Principal Investigator: Otto Lesch, MD, Prof., Department of Psychiatry, University of Wien
  • Study Director: Giovanni Addolorato, MD, Department of Internal Medicine, Catholic University of Rome

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

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

February 1, 2002

Primary Completion (Actual)

April 1, 2009

Study Completion (Actual)

May 1, 2009

Study Registration Dates

First Submitted

March 17, 2014

First Submitted That Met QC Criteria

March 17, 2014

First Posted (Estimate)

March 18, 2014

Study Record Updates

Last Update Posted (Estimate)

March 18, 2014

Last Update Submitted That Met QC Criteria

March 17, 2014

Last Verified

March 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GATE-I

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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