Clinical trial NCT02090504: Comparative Study of Gamma-hydroxy Butyrate Versus Oxazepam in the Treatment of Alcohol Withdrawal Syndrome
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Alcohol Withdrawal Syndrome
Alcohol Dependence
Keywords: alcohol withdrawal syndrome
treatment
sodium oxybate
oxazepam
Lead sponsor: Catholic University of the Sacred Heart
Sponsor class: OTHER
Collaborators: name: CT Pharmaceutical Industries, Sanremo - Italy
name: University of Bologna
name: Medical University of Vienna
First posted: 2014-03-18
Enrollment: 127
Sex: ALL
Minimum age (years): 21
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Efficacy of GHB compared to oxazepam on alcohol withdrawal symptoms
timeFrame: day 1, day 10, day 20
Secondary outcomes:
measure: Course of alcohol abstinence
timeFrame: day 1, day 10, day 20
Other outcomes:
measure: Craving for study drug.
timeFrame: day 1, day 10, day 20
Locations:
city: Wien
country: Austria
facility: University of Wien
state: AT
city: Bologna
country: Italy
facility: "G. Fontana" Centre for the Study and Multidisciplinary Treatment of Alcohol Addiction, Department of Clinical Medicine, University of Bologna
state: BO
city: Rome
country: Italy
facility: Catholic University of Rome
state: Rm
Study officials:
affiliation: Department of Psychiatry, University of Wien
name: Otto Lesch, MD, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Internal Medicine, Catholic University of Rome
name: Giovanni Addolorato, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Caputo F, Skala K, Mirijello A, Ferrulli A, Walter H, Lesch O, Addolorato G. Sodium oxybate in the treatment of alcohol withdrawal syndrome: a randomized double-blind comparative study versus oxazepam. The GATE 1 trial. CNS Drugs. 2014 Aug;28(8):743-52. doi: 10.1007/s40263-014-0183-1.