Evaluation of the Efficacy of Sodium Oxybate in the Long-term Maintenance of Abstinence in Alcoholic Patients

Alcohol Dependence Clinical Trial

— GATE2  

Official title:

Multinational, Multicentre, Double-blind, Placebo-controlled Evaluation of the Efficacy of GHB in the Long-term Maintenance of Abstinence in Alcoholic Patients After the Initial Weaning Phase, Stratified by Lesch's Taxonomy (GATE 2)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04648423
• Other study ID #: GHBCR00/2
• Status: Completed
• Phase: Phase 4
• Start date: July 23, 2001
• Est. completion date: January 2012

Study information

• Verified date: November 2020
• Source: Laboratorio Farmaceutico Ct S.r.l.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Additional pharmacotherapies in the treatment of alcohol dependence are needed. Sodium oxybate showed efficacy in the maintenance of abstinence in alcohol-dependent patients in several small randomized trials of short duration. The aim of the present phase III/IV study is to confirm in a randomized-controlled study the efficacy and safety of oral sodium oxybate in the maintenance of abstinence.

Description:

Alcohol dependence (AD) is the most severe form of alcohol use disorder. It occurs in 2.6% of people aged 15+ years worldwide and can result in a reduction of life-expectancy by several years as compared with the general population. Currently, disulfiram, acamprosate and naltrexone are the main medicinal products registered for the maintenance of abstinence in AD patients. Although effective on the group level, effects sizes are limited, and many AD patients fail to respond to these medications. Therefore, additional pharmacological treatments are needed. Sodium oxybate 50mg/kg/day showed evidence of efficacy compared to placebo and naltrexone in the maintenance of abstinence in AD patients in a series of open label and blinded randomized controlled trials (RCTs). However, studies were generally small and did not investigate the sustainability of the Sodium oxybate effect post-treatment. The present phase III/IV RCT (GATE 2) aimed to confirm the efficacy and safety of oral Sodium oxybate in the maintenance of abstinence. Secondary aims included the assessment of sustained SMO effects during the 6-month medication free period immediately following the 6-month treatment period and monitoring the risk of Sodium oxybate dependence.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 314
• Est. completion date: January 2012
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 75 Years

Eligibility

Inclusion Criteria:

The following subjects were recruited:

• males and females;
• of any ethnic group;
• age between 21 and 75 years at recruitment;
• documented alcohol dependency before weaning detected according to the CAGE instrument, classified according to the DSM-IV and ICD-10 and severity rated according to the MALT instrument;
• classified according to Lesch typology;
• having successfully undergone a detoxification program, encompassing a 10-day treatment period and a subsequent 10-day untreated follow-up;
• with a responsible relative or caregiver;
• having issued the informed consent.

Exclusion Criteria:

• subjects who did not quit alcohol drinking after the detoxification period;
• subjects with history of epilepsy or epileptics seizures not properly controlled by established anti-epileptic treatment;
• subjects with dependence from narcotics or other drugs of abuse;
• subjects without a stable address;
• subjects without a reference relative or caregiver;
• subjects with renai failure (blood creatinine >2.5 mg/dL and/or documented proteinuria >500 mg/day);
• subjects with heart failure or severe respiratory failure;
• subjects with hepatic encephalopathy stage lI-IV;
• subjects with severe psychiatric disorders requiring treatment with psychoactive medications (excluding short-term benzodiazepine treatments);
• subjects under treatment with clonidine, disulfiram (after the end of the detoxification period), haloperidol, bromocryptine, serotonine re-uptake inhibitors or other serotoninergic agents;
• female subjects who cannot assure not to become pregnant during the 7-month period covering treatment and the first treatment-free month of follow-up;
• documented pre-existent hypersensitivity to GHB;
• subjects unable or unwilling to issue the informed consent;
• participating to another clinica! investigation in the previous month prior to recruitment; 15. any other medicai condition which, according to the investigator, justifies the patient's exclusion from the study.

Related Conditions & MeSH terms

• Alcohol Dependence
• Alcohol Use Disorder (AUD)
• Alcoholism

Intervention

Drug:
• Sodium Oxybate
solution for oral administration
• Placebo
solution for oral administration

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Laboratorio Farmaceutico Ct S.r.l.

References & 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. — View Citation

van den Brink W, Addolorato G, Aubin HJ, Benyamina A, Caputo F, Dematteis M, Gual A, Lesch OM, Mann K, Maremmani I, Nutt D, Paille F, Perney P, Rehm J, Reynaud M, Simon N, Söderpalm B, Sommer WH, Walter H, Spanagel R. Efficacy and safety of sodium oxybate — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative Abstinence Duration (CAD)	to demonstrate that sodium oxybate is superior to placebo in the CAD during the treatment period.	6-month treatment period
Secondary	CAD stratified	CAD during treatment period according to subtype patients stratified by Lesch's categories.	6-month treatment period
Secondary	Assessment of the exposure-corrected CAD	assessment of the exposure-corrected cumulative abstinence duration (CCAD) during treatment.	6-month treatment period
Secondary	CAD during the whole study	CAD during the whole observation period	12 months: 6-month treatment period + 6-month follow-up
Secondary	Proportion of abstinent patients	proportion of abstinent patients at the end of the 6-month treatment period and at the end of the entire observation period.	12 months: 6-month treatment period + 6-month follow-up
Secondary	Time to the first relapse	assessment of the time to the first relapse during the treatment period.	6-month treatment period
Secondary	Change from baseline in the craving for alcohol intensity and frequency by the Lubecker Craving Risiko Ruckfall (LCRR) questionnaire.	The LCRR provides the patient's current state about his craving for alcohol. The clinician interviews the patient to rate the intensity of the desire for alcohol (item-1) on a 4-point scale ranging from 1 (no desire) to 4 (very strong desire), and to rate the frequency of the desire for alcohol (item-2) on a 6-point scale ranging from 1 (never) to 6 (nearly continuous).; Higher scores mean a worse outcome.	12 months: 6-month treatment period + 6-month follow-up
Secondary	Assessment of the time course of ?-GT as biological marker of alcohol abuse, during treatment and at the end of follow-up.	?-GT values	Month 6
Secondary	Adverse events	evaluation of the frequency, nature and severity of adverse clinical events, including mortality and morbidity	6-month treatment period
Secondary	Number of participants with Adverse Events (AEs)	Overview of AEs.	6-month treatment period
Secondary	Risk of Secondary Dependence - treatment period	Evaluation of the risk of onset of dependence from the medication, by means of a 2-item questionnaire. The first to rate the intensity of the desire for medication since the last visit in a scale ranging from 0 to 100. The second to rate the approach to the next dose in a scale ranging from 1 (I just waited for the time to come) to 6 (I took the dose sooner than planned).; Higher scores mean a worse outcome.	6-month treatment period
Secondary	Assessment of the time course of MCV as biological marker of alcohol abuse, during treatment and at the end of follow-up.	MCV values	Month 6