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

Primary Purpose

Alcohol Withdrawal Syndrome, Alcohol Dependence

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Sodium Oxybate (SMO)
Oxazepam
Sponsored by
Catholic University of the Sacred Heart
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alcohol Withdrawal Syndrome focused on measuring alcohol withdrawal syndrome, treatment, sodium oxybate, oxazepam

Eligibility Criteria

21 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Sodium oxybate (SMO)

Oxazepam

Arm Description

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.

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).

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.

Full Information

First Posted
March 17, 2014
Last Updated
March 17, 2014
Sponsor
Catholic University of the Sacred Heart
Collaborators
CT Pharmaceutical Industries, Sanremo - Italy, University of Bologna, Medical University of Vienna
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1. Study Identification

Unique Protocol Identification Number
NCT02090504
Brief Title
Comparative Study of Gamma-hydroxy Butyrate Versus Oxazepam in the Treatment of Alcohol Withdrawal Syndrome
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
February 2002 (undefined)
Primary Completion Date
April 2009 (Actual)
Study Completion Date
May 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Catholic University of the Sacred Heart
Collaborators
CT Pharmaceutical Industries, Sanremo - Italy, University of Bologna, Medical University of Vienna

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Withdrawal Syndrome, Alcohol Dependence
Keywords
alcohol withdrawal syndrome, treatment, sodium oxybate, oxazepam

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
127 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sodium oxybate (SMO)
Arm Type
Experimental
Arm Description
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.
Arm Title
Oxazepam
Arm Type
Active Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Sodium Oxybate (SMO)
Other Intervention Name(s)
Gamma-hydroxy butyrate (GHB)
Intervention Type
Drug
Intervention Name(s)
Oxazepam
Primary Outcome Measure Information:
Title
Efficacy of GHB compared to oxazepam on alcohol withdrawal symptoms
Description
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).
Time Frame
day 1, day 10, day 20
Secondary Outcome Measure Information:
Title
Course of alcohol abstinence
Description
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.
Time Frame
day 1, day 10, day 20
Other Pre-specified Outcome Measures:
Title
Craving for study drug.
Description
Assessment of craving for the study drug.
Time Frame
day 1, day 10, day 20

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Otto Lesch, MD, Prof.
Organizational Affiliation
Department of Psychiatry, University of Wien
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Giovanni Addolorato, MD
Organizational Affiliation
Department of Internal Medicine, Catholic University of Rome
Official's Role
Study Director
Facility Information:
Facility Name
University of Wien
City
Wien
State/Province
AT
Country
Austria
Facility Name
"G. Fontana" Centre for the Study and Multidisciplinary Treatment of Alcohol Addiction, Department of Clinical Medicine, University of Bologna
City
Bologna
State/Province
BO
Country
Italy
Facility Name
Catholic University of Rome
City
Rome
State/Province
Rm
ZIP/Postal Code
00168
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
24283802
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.
Results Reference
background
PubMed Identifier
24996524
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.
Results Reference
derived

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

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