Alcohol Withdrawal SyndromePhase 4GATE INCT02090504
Comparative Study of Gamma-hydroxy Butyrate Versus Oxazepam in the Treatment of Alcohol Withdrawal Syndrome
A Phase 4 study testing Sodium Oxybate (SMO) and Oxazepam in people with Alcohol Withdrawal Syndrome and Alcohol Dependence, run by Catholic University of the Sacred Heart at 3 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 75 years
- Conditions the study is for
- Alcohol Withdrawal Syndrome, Alcohol Dependence
- What is being tested?
- Sodium Oxybate (SMO) and Oxazepam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 127 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Feb 2002to May 2009
- 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
- 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.
Who cannot join
- ≤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),
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- 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.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Italy2 sites
"G. Fontana" Centre for the Study and Multidisciplinary Treatment of Alcohol Addiction, Department of Clinical Medicine, University of Bologna
Bologna, BO
Catholic University of Rome
Rome, Rm, 00168
About this study
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
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).
Read the 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.
- Conditions
- Alcohol Withdrawal Syndrome, Alcohol Dependence
- Being tested
- Sodium Oxybate (SMO), Oxazepam
- Keywords
- alcohol withdrawal syndrome, treatment, sodium oxybate, oxazepam
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium Oxybate (SMO)Drug
Also called Gamma-hydroxy butyrate (GHB)
OxazepamDrug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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). Receives: Drug: Oxazepam |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: day 1, day 10, day 20
Secondary outcomes (1)
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.
Measured: day 1, day 10, day 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2014 (estimated)
- Study startFeb 2002
- Primary completionApr 2009
- Study completionMay 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Alcohol Withdrawal SyndromeStudies 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Lead sponsor
- Catholic University of the Sacred Heart
- Sponsor type
- University, hospital or other
- Collaborators
- CT Pharmaceutical Industries, Sanremo - Italy, University of Bologna, Medical University of Vienna
- Responsible party
- Principal investigator, Giovanni Addolorato, Catholic University, Italy
- Investigators
- Otto Lesch, MD, Prof., Principal investigator, Department of Psychiatry, University of WienGiovanni Addolorato, MD, Study director, Department of Internal Medicine, Catholic University of Rome
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02090504
- Sponsor's protocol ID
- GATE-I
- Acronym
- GATE I
- Status last verified
- Mar 2014
- First submitted
- 17 Mar 2014
- Last updated
- 18 Mar 2014
- Results posted
- No
- Data monitoring committee
- 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 24283802Caputo 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.
PubMed 24996524
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02090504
- Acronym / sponsor ID
- GATE I / GATE-I
- Conditions
- Alcohol Withdrawal Syndrome, Alcohol Dependence
- Keywords
- alcohol withdrawal syndrome, treatment, sodium oxybate, oxazepam
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 127 participants (actual)
- Lead sponsor
- Catholic University of the Sacred HeartUniversity, hospital or other
- Collaborators
- CT Pharmaceutical Industries, Sanremo - Italy, University of Bologna, Medical University of Vienna
- Study start
- Feb 2002
- Primary completion
- Apr 2009 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 18 Mar 2014 (estimated)
- 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sodium oxybate (SMO) | Experimental | Drug: Sodium Oxybate (SMO)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. |
| Oxazepam | Active comparator | Drug: OxazepamPatients 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). |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (14 listed)
- ≤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,
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 Oxybate (SMO)Also: Gamma-hydroxy butyrate (GHB) | Drug | Sodium oxybate (SMO) |
| Oxazepam | Drug | Oxazepam |
Primary outcome
Efficacy of GHB compared to oxazepam on alcohol withdrawal symptoms
Time frame: day 1, day 10, day 20
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).
1 secondary outcome
Course of alcohol abstinence
Time frame: day 1, day 10, day 20
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 18 Mar 2014.
- Background: 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.
- Derived from this study: PubMed 24996524Caputo 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.
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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.
Otto Lesch, MD, Prof. principal investigator
Department of Psychiatry, University of Wien
Giovanni Addolorato, MD study director
Department of Internal Medicine, Catholic University of Rome
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sodium Oxybate (SMO) and Oxazepam in people with Alcohol Withdrawal Syndrome and Alcohol Dependence, run by Catholic University of the Sacred Heart at 3 sites in 2 countries.
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 3 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 18 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Italy, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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?
Efficacy of GHB compared to oxazepam on alcohol withdrawal symptoms (time frame: day 1, day 10, day 20). 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 NCT02090504, which also lists 2 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 18 Mar 2014.