Back to resultsEvaluation of the Efficacy of Sodium Oxybate in the Long-term Maintenance of Abstinence in Alcoholic Patients (GATE2)
Primary Purpose
Alcohol Use Disorder (AUD), Alcohol Dependence
Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Sodium Oxybate
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Alcohol Use Disorder (AUD) focused on measuring alcoholism, alcohol, alcohol dependence, relapse prevention
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
sodium oxybate
placebo
Arm Description
Sodium oxybate solution for oral administration (175 mg/mL). Dose (body weight ≤ 65 kg): 19.0 mL daily, in 3 administrations, for 6 months Dose (body weight > 65 kg): 22.5 mL daily, in 3 administrations, for 6 months
Placebo solution for oral administration. Dose (body weight ≤ 65 kg): 19.0 mL daily, in 3 administrations, for 6 months Dose (body weight > 65 kg): 22.5 mL daily, in 3 administrations, for 6 months
Outcomes
Primary Outcome Measures
Cumulative Abstinence Duration (CAD)
to demonstrate that sodium oxybate is superior to placebo in the CAD during the treatment period.
Secondary Outcome Measures
CAD stratified
CAD during treatment period according to subtype patients stratified by Lesch's categories.
Assessment of the exposure-corrected CAD
assessment of the exposure-corrected cumulative abstinence duration (CCAD) during treatment.
CAD during the whole study
CAD during the whole observation period
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.
Time to the first relapse
assessment of the time to the first relapse during the treatment period.
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.
Assessment of the time course of γ-GT as biological marker of alcohol abuse, during treatment and at the end of follow-up.
γ-GT values
Adverse events
evaluation of the frequency, nature and severity of adverse clinical events, including mortality and morbidity
Number of participants with Adverse Events (AEs)
Overview of AEs.
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.
Assessment of the time course of MCV as biological marker of alcohol abuse, during treatment and at the end of follow-up.
MCV values
Full Information
NCT ID
NCT04648423
First Posted
November 16, 2020
Last Updated
December 2, 2020
Sponsor
Laboratorio Farmaceutico Ct S.r.l.
1. Study Identification
Unique Protocol Identification Number
NCT04648423
Brief Title
Evaluation of the Efficacy of Sodium Oxybate in the Long-term Maintenance of Abstinence in Alcoholic Patients
Acronym
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)
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
July 23, 2001 (Actual)
Primary Completion Date
March 2011 (Actual)
Study Completion Date
January 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Laboratorio Farmaceutico Ct S.r.l.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Use Disorder (AUD), Alcohol Dependence
Keywords
alcoholism, alcohol, alcohol dependence, relapse prevention
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
double-blind, placebo-controlled study with parallel group
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The control medication (placebo) was identically-looking and identically tasting as active.
Allocation
Randomized
Enrollment
314 (Actual)
8. Arms, Groups, and Interventions
Arm Title
sodium oxybate
Arm Type
Experimental
Arm Description
Sodium oxybate solution for oral administration (175 mg/mL). Dose (body weight ≤ 65 kg): 19.0 mL daily, in 3 administrations, for 6 months Dose (body weight > 65 kg): 22.5 mL daily, in 3 administrations, for 6 months
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Placebo solution for oral administration. Dose (body weight ≤ 65 kg): 19.0 mL daily, in 3 administrations, for 6 months Dose (body weight > 65 kg): 22.5 mL daily, in 3 administrations, for 6 months
Intervention Type
Drug
Intervention Name(s)
Sodium Oxybate
Other Intervention Name(s)
gamma-hydroxy butyrate (GHB)
Intervention Description
solution for oral administration
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
solution for oral administration
Primary Outcome Measure Information:
Title
Cumulative Abstinence Duration (CAD)
Description
to demonstrate that sodium oxybate is superior to placebo in the CAD during the treatment period.
Time Frame
6-month treatment period
Secondary Outcome Measure Information:
Title
CAD stratified
Description
CAD during treatment period according to subtype patients stratified by Lesch's categories.
Time Frame
6-month treatment period
Title
Assessment of the exposure-corrected CAD
Description
assessment of the exposure-corrected cumulative abstinence duration (CCAD) during treatment.
Time Frame
6-month treatment period
Title
CAD during the whole study
Description
CAD during the whole observation period
Time Frame
12 months: 6-month treatment period + 6-month follow-up
Title
Proportion of abstinent patients
Description
proportion of abstinent patients at the end of the 6-month treatment period and at the end of the entire observation period.
Time Frame
12 months: 6-month treatment period + 6-month follow-up
Title
Time to the first relapse
Description
assessment of the time to the first relapse during the treatment period.
Time Frame
6-month treatment period
Title
Change from baseline in the craving for alcohol intensity and frequency by the Lubecker Craving Risiko Ruckfall (LCRR) questionnaire.
Description
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.
Time Frame
12 months: 6-month treatment period + 6-month follow-up
Title
Assessment of the time course of γ-GT as biological marker of alcohol abuse, during treatment and at the end of follow-up.
Description
γ-GT values
Time Frame
Month 6
Title
Adverse events
Description
evaluation of the frequency, nature and severity of adverse clinical events, including mortality and morbidity
Time Frame
6-month treatment period
Title
Number of participants with Adverse Events (AEs)
Description
Overview of AEs.
Time Frame
6-month treatment period
Title
Risk of Secondary Dependence - treatment period
Description
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.
Time Frame
6-month treatment period
Title
Assessment of the time course of MCV as biological marker of alcohol abuse, during treatment and at the end of follow-up.
Description
MCV values
Time Frame
Month 6
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:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roberto Cacciaglia
Organizational Affiliation
Laboratorio Farmaceutico C.T.
Official's Role
Study Chair
12. IPD Sharing Statement
Plan to Share IPD
No
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
result
PubMed Identifier
30043457
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, Soderpalm B, Sommer WH, Walter H, Spanagel R. Efficacy and safety of sodium oxybate in alcohol-dependent patients with a very high drinking risk level. Addict Biol. 2018 Jul;23(4):969-986. doi: 10.1111/adb.12645.
Results Reference
result
PubMed Identifier
35796481
Citation
Guiraud J, Addolorato G, Antonelli M, Aubin HJ, de Bejczy A, Benyamina A, Cacciaglia R, Caputo F, Dematteis M, Ferrulli A, Goudriaan AE, Gual A, Lesch OM, Maremmani I, Mirijello A, Nutt DJ, Paille F, Perney P, Poulnais R, Raffaillac Q, Rehm J, Rolland B, Rotondo C, Scherrer B, Simon N, Skala K, Soderpalm B, Somaini L, Sommer WH, Spanagel R, Vassallo GA, Walter H, van den Brink W. Sodium oxybate for the maintenance of abstinence in alcohol-dependent patients: An international, multicenter, randomized, double-blind, placebo-controlled trial. J Psychopharmacol. 2022 Oct;36(10):1136-1145. doi: 10.1177/02698811221104063. Epub 2022 Jul 7.
Results Reference
derived
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Evaluation of the Efficacy of Sodium Oxybate in the Long-term Maintenance of Abstinence in Alcoholic Patients
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