Comparative Study of Gamma-hydroxy Butyrate Versus Oxazepam in the Treatment of Alcohol Withdrawal Syndrome

Alcohol Dependence Clinical Trial

— GATE I  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02090504
• Other study ID #: GATE-I
• Status: Completed
• Phase: Phase 4
• First received: March 17, 2014
• Last updated: March 17, 2014
• Start date: February 2002
• Est. completion date: May 2009

Study information

• Verified date: March 2014
• Source: Catholic University of the Sacred Heart
• Contact: n/a
• Is FDA regulated: No
• Health authority: European Union: European Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 127
• Est. completion date: May 2009
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alcohol Dependence
• Alcohol Withdrawal Syndrome
• Alcoholism
• Substance Withdrawal Syndrome
• Syndrome

Intervention

Drug:
• Sodium Oxybate (SMO)

• Oxazepam

Locations

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

Sponsors (4)

Lead Sponsor	Collaborator
Catholic University of the Sacred Heart	CT Pharmaceutical Industries, Sanremo - Italy, Medical University of Vienna, University of Bologna

Countries where clinical trial is conducted

Austria,  Italy, 

References & Publications (1)

Skala K, Caputo F, Mirijello A, Vassallo G, Antonelli M, Ferrulli A, Walter H, Lesch O, Addolorato G. Sodium oxybate in the treatment of alcohol dependence: from the alcohol withdrawal syndrome to the alcohol relapse prevention. Expert Opin Pharmacother. 2014 Feb;15(2):245-57. doi: 10.1517/14656566.2014.863278. Epub 2013 Nov 28. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Craving for study drug.	Assessment of craving for the study drug.	day 1, day 10, day 20	No
Primary	Efficacy of GHB compared to oxazepam on alcohol withdrawal symptoms	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	No
Secondary	Course of alcohol abstinence	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	Yes