Alcohol Use Disorder (AUD)Phase 4GATE2NCT04648423

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

A Phase 4 study testing Sodium Oxybate in people with Alcohol Use Disorder (AUD) and Alcohol Dependence, run by Laboratorio Farmaceutico Ct S.r.l..

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 21 to 75 years
Conditions the study is for: Alcohol Use Disorder (AUD), Alcohol Dependence
What is being tested?: Sodium Oxybate
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 314 participants
Where: No sites listed yet
Study dates: 23 Jul 2001to Jan 2012
Phase: Phase 4
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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;

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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.

Who cannot join

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);

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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.

About this study

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)

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.

Read the 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.

Conditions: Alcohol Use Disorder (AUD), Alcohol Dependence
Being tested: Sodium Oxybate, Placebo
Keywords: alcoholism, alcohol, alcohol dependence, relapse prevention
Medical subject headings: Alcoholism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Sodium OxybateDrug
Also called gamma-hydroxy butyrate (GHB)
solution for oral administration
PlaceboDrug
solution for oral administration

Study groups in NCT04648423
Study group	Role	What they receive
sodium oxybate	Experimental	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 Receives: Drug: Sodium Oxybate
placebo	Placebo comparator	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 Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Cumulative Abstinence Duration (CAD)
to demonstrate that sodium oxybate is superior to placebo in the CAD during the treatment period.
Measured: 6-month treatment period

Secondary outcomes (11)

CAD stratified
CAD during treatment period according to subtype patients stratified by Lesch's categories.
Measured: 6-month treatment period
Assessment of the exposure-corrected CAD
assessment of the exposure-corrected cumulative abstinence duration (CCAD) during treatment.
Measured: 6-month treatment period
CAD during the whole study
CAD during the whole observation period
Measured: 12 months: 6-month treatment period + 6-month follow-up
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.
Measured: 12 months: 6-month treatment period + 6-month follow-up
Time to the first relapse
assessment of the time to the first relapse during the treatment period.
Measured: 6-month 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.
Measured: 12 months: 6-month treatment period + 6-month follow-up
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
Measured: Month 6
Adverse events
evaluation of the frequency, nature and severity of adverse clinical events, including mortality and morbidity
Measured: 6-month treatment period
Number of participants with Adverse Events (AEs)
Overview of AEs.
Measured: 6-month treatment period
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.
Measured: 6-month treatment period
Assessment of the time course of MCV as biological marker of alcohol abuse, during treatment and at the end of follow-up.
MCV values
Measured: Month 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Jul 2001Jan 2012

First posted1 Dec 2020
Study start23 Jul 2001
Primary completionMar 2011
Study completionJan 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Alcohol Use Disorder (AUD)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: double-blind, placebo-controlled study with parallel group
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 314 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04648423
Sponsor's protocol ID: GHBCR00/2
Acronym: GATE2
Status last verified: Nov 2020
First submitted: 16 Nov 2020
Last updated: 4 Dec 2020
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 24283802
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.
PubMed 30043457
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.
PubMed 35796481

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 4 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT04648423
Acronym / sponsor ID: GATE2 / GHBCR00/2
Conditions: Alcohol Use Disorder (AUD), Alcohol Dependence
Keywords: alcoholism, alcohol, alcohol dependence, relapse prevention
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 314 participants (actual)
Lead sponsor: Laboratorio Farmaceutico Ct S.r.l.Industry (pharma, biotech, devices)
Study start: 23 Jul 2001 (actual)
Primary completion: Mar 2011 (actual)
Study completion: Jan 2012 (actual)
First posted: 1 Dec 2020 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: double-blind, placebo-controlled study with parallel group

Arm	Type	Receives
sodium oxybate	Experimental	Drug: Sodium OxybateSodium 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	Placebo comparator	Drug: PlaceboPlacebo 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

Who may qualify

Ages: 21 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

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;

Key exclusion criteria (14 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Sodium OxybateAlso: gamma-hydroxy butyrate (GHB)solution for oral administration	Drug	sodium oxybate
Placebosolution for oral administration	Drug	placebo

Primary outcome

Cumulative Abstinence Duration (CAD)
Time frame: 6-month treatment period
to demonstrate that sodium oxybate is superior to placebo in the CAD during the treatment period.

11 secondary outcomes

CAD stratified
Time frame: 6-month treatment period
Assessment of the exposure-corrected CAD
Time frame: 6-month treatment period
CAD during the whole study
Time frame: 12 months: 6-month treatment period + 6-month follow-up
Proportion of abstinent patients
Time frame: 12 months: 6-month treatment period + 6-month follow-up
Time to the first relapse
Time frame: 6-month treatment period
Change from baseline in the craving for alcohol intensity and frequency by the Lubecker Craving Risiko Ruckfall (LCRR) questionnaire.
Time frame: 12 months: 6-month treatment period + 6-month follow-up
Assessment of the time course of γ-GT as biological marker of alcohol abuse, during treatment and at the end of follow-up.
Time frame: Month 6
Adverse events
Time frame: 6-month treatment period
Number of participants with Adverse Events (AEs)
Time frame: 6-month treatment period
Risk of Secondary Dependence - treatment period
Time frame: 6-month treatment period
Assessment of the time course of MCV as biological marker of alcohol abuse, during treatment and at the end of follow-up.
Time frame: Month 6

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2020.
Results publication: PubMed 24283802Skala 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 publication: PubMed 30043457van 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.
Derived from this study: PubMed 35796481Guiraud 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Roberto Cacciaglia study chair

Laboratorio Farmaceutico C.T.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Sodium Oxybate in people with Alcohol Use Disorder (AUD) and Alcohol Dependence, run by Laboratorio Farmaceutico Ct S.r.l..

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cumulative Abstinence Duration (CAD) (time frame: 6-month treatment period). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04648423, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2020.