NCT02090504

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).

Trial Health

90
On Track

Trial Health Score

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

Enrollment
127

participants targeted

Target at P50-P75 for phase_4

Timeline
Completed

Started Feb 2002

Longer than P75 for phase_4

Geographic Reach
2 countries

3 active sites

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

February 1, 2002

Completed
7.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2009

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2009

Completed
4.9 years until next milestone

First Submitted

Initial submission to the registry

March 17, 2014

Completed
1 day until next milestone

First Posted

Study publicly available on registry

March 18, 2014

Completed
Last Updated

March 18, 2014

Status Verified

March 1, 2014

Enrollment Period

7.2 years

First QC Date

March 17, 2014

Last Update Submit

March 17, 2014

Conditions

Alcohol Withdrawal SyndromeAlcohol Dependence

Keywords

alcohol withdrawal syndrometreatmentsodium oxybateoxazepam

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (1)

  • Course of alcohol abstinence

    day 1, day 10, day 20

Other Outcomes (1)

  • Craving for study drug.

    day 1, day 10, day 20

Study Arms (2)

Sodium oxybate (SMO)

EXPERIMENTAL

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)

Oxazepam

ACTIVE COMPARATOR

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

Interventions

Sodium Oxybate (SMO)DRUG
Also known as: Gamma-hydroxy butyrate (GHB)
Sodium oxybate (SMO)
OxazepamDRUG
Oxazepam

Eligibility Criteria

Age21 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • ≤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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

University of Wien

Vienna, AT, Austria

Location

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

Bologna, BO, Italy

Location

Catholic University of Rome

Rome, Rm, 00168, Italy

Location

Related Publications (2)

  • 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.

    PMID: 24283802BACKGROUND

  • 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.

    PMID: 24996524DERIVED

MeSH Terms

Conditions

Alcoholism

Interventions

Sodium OxybateOxazepam

Condition Hierarchy (Ancestors)

Alcohol-Related DisordersSubstance-Related DisordersChemically-Induced DisordersMental Disorders

Intervention Hierarchy (Ancestors)

HydroxybutyratesButyratesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsHydroxy AcidsBenzodiazepinonesBenzodiazepinesBenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Otto Lesch, MD, Prof.

    Department of Psychiatry, University of Wien

    PRINCIPAL INVESTIGATOR

  • Giovanni Addolorato, MD

    Department of Internal Medicine, Catholic University of Rome

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 4
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
Professor of Internal Medicine

Study Record Dates

First Submitted

March 17, 2014

First Posted

March 18, 2014

Study Start

February 1, 2002

Primary Completion

April 1, 2009

Study Completion

May 1, 2009

Last Updated

March 18, 2014

Record last verified: 2014-03

Locations

IT(2)AU(1)