Alcohol DependencePhase 2/3NCT00262639
Prometa Protocol for Alcohol Dependence
A Phase 2/3 study testing Flumazenil and Gabapentin in people with Alcohol Dependence, run by Medical University of South Carolina at 1 site in United States.
Trial summary
This is a placebo controlled trial (some people receive active and some people receive inactive medication) to evaluate the effectiveness of a new protocol to treat alcohol dependence. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Alcohol Dependence
- What is being tested?
- Flumazenil and Gabapentin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2005to Mar 2008
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 - 70.
- Participants will meet criteria for primary DSM IV alcohol dependence, drink on at least 70% of days in the last 30 days prior to assessment, and drink at least 5 drinks per drinking day.
- No more than 72 hours since last drink of alcohol. Rationale: to focus on symptoms occurring during the early alcohol cessation period.
- Low CIWA-Ar group: have a CIWA-Ar score less than or equal to 6; High CIWA-Ar group: have a CIWA-Ar score greater than or equal to 7 but less than or equal to 15.
- Able to read and understand questionnaires and informed consent.
- Has stable housing for past 3 months.
Who cannot join
- Currently meets DSM-IV criteria for any other psychoactive substance dependence disorder except nicotine dependence.
- Any psychoactive substance abuse, except marijuana and nicotine, within the last 30 days as evidenced by subject report or urine drug screen.
- Meets DSM-IV criteria for current axis I disorders of major depression, panic disorder, obsessive-compulsive disorder, generalized anxiety disorder, post-traumatic stress syndrome, bipolar affective disorder, schizophrenia, or any other psychotic disorder or organic mental disorder. The rationale for excluding them is that symptoms from these disorders may affect dependent variables and complicate interpretation of the data.
- No use of benzodiazepines in excess of three times in the past two weeks by self report and urine drug screen.
- Subjects must not be taking zolpidem (Ambien™), zaleplon (Sonata™), or eszopiclone (Lunesta™) in excess of three times in past two weeks.
- No history of delirium tremens or alcohol withdrawal seizures.
Show all 15Show fewer
- Has current suicidal ideation with plan or homicidal ideation.
- Need for maintenance or acute treatment with any psychoactive medication including antiseizure medications.
- Use of disulfiram, naltrexone, acamprosate, or anticonvulsants in last 30 days.
- Clinically significant medical problems such as cardiovascular, renal, GI, or endocrine problem that would impair participation or limit medication ingestion.
- Sexually active females of child-bearing potential who are pregnant (by -beta HCG), nursing, or who are not using a reliable form of birth control.
- Has current charges pending for a violent crime (not including DUI related offenses).
- Has taken gabapentin or flumazenil in the last month or has experienced adverse effects from it at any time in the past.
- Hepatocellular disease indicated by elevations of SGPT (ALT) and SGOT (AST) greater than 3 times normal at screening.
- Persons with metal implants or pacemaker since fMRI will be used.
Trial locations and contacts
1 site in 1 country.
United States1 site
MUSC-Center for Drug and Alcohol Programs
Charleston, South Carolina, 29425
About this study
Official title: A Double Blind Evaluation of Flumazenil and Gabapentin for the Treatment of Alcohol Withdrawal and Relapse Prevention
This is a placebo controlled trial (some people receive active and some people receive inactive medication) to evaluate the effectiveness of a new protocol to treat alcohol dependence. Two main medications (plus ancillary non-placebo controlled medications) and their placebos (inactive drugs) will be utilized to treat both alcohol withdrawal, promote abstinence, and reduce drinking over approximately a six-week treatment period. All participants will meet criteria for Alcohol Dependence and be drinking heavily up until 72 hours prior to receiving the first study drug. They will be injected one drug (flumazenil or placebo) over a two day period and receive the second one (gabapentin or placebo) by mouth for 39 days. The main hypothesis is that this protocol will reduce early alcohol withdrawal symptoms and will reduce relapse to drinking and promote abstinence compared to the placebo (inactive) drug group. Secondary outcomes that will be evaluated include reduction in craving, improvement in sleep, brain activity and mood.
Read the detailed description
Approximately 60 alcohol dependent individuals who are drinking heavily up until 72 hours, or less, prior to study participation will be randomized to receive either flumazenil (intravenously)on two successive days and gabapentin (orally)for 39 days or their matching placebos. They also will receive hydroxyzine and vitamins. Individuals will be evaluated for alcohol withdrawal, their response to acoustic startle, cognitive ability, craving, mood, sleep and drinking during the first week. They will then be seen weekly for about 6 weeks during which they take gabapentin or placebo and are provided with Combined Behavioral Intervention Therapy (counseling) once a week, or more, as required. Over this period they will be evaluated weekly for alcohol consumption, craving, sleep, mood, and biological markers of alcohol consumption ( percent carbohydrate deficient transferrin and gamma-glutamyl transferase). Blood will be obtained on week 3 and 6 for general health (liver, blood count etc.) screening. After the end of treatment, subjects will be followed-up at 4 weeks and again at 8 weeks after treatment to evaluate alcohol consumption, craving, sleep, mood.
Subjects will undergo a functional magnetic resonance imaging (MRI) procedure sometime during the second or third week of study medication to assess cue induced regional brain activation to investigate the effect of medication on brain response to alcohol visual cues.
- Conditions
- Alcohol Dependence
- Being tested
- Flumazenil and Gabapentin, Placebo
- Keywords
- Alcoholism, Alcohol Dependence, Alcohol Withdrawal, Treatment, Pharmacotherapy
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Flumazenil and GabapentinDrug
2 mg flumazenil for infusion given slowly over 20 minutes given day 1 and day 2 gabapentin 300 mg increasing to 1200 mg over 4 days and continuing to day 30. Gabapentin 900 mg Day 31 to Day 33 gabapentin 600 mg Day 34 to 36 and gabapentin 300 mg Day 37 to 39.
PlaceboDrug
20 mg Saline infused slowly over 20 minutes. Placebo 1 capsule Day 1, 2 capsules Day 2, 3 capsules Day 3, 4 capsules days 4 to 30; 3 capsules Day 31 to 33; 2 capsules day 34 to 36 and 1 capsule 37 to 39.
| Study group | Role | What they receive |
|---|---|---|
| I | Experimental | 2 mg flumazenil given over 20 minutes on Day 1 and Day 2. Gabapentin 300 mg Day 1; gabapentin 600 mg Day 2; gabapentin 900 mg Day 3; gabapentin 1200 mg Day 4 to 30; gabapentin 900 mg day 31-33; gabapentin 600 mg day 34-36; gabapentin 300 mg day 37-39. Receives: Drug: Flumazenil and Gabapentin |
| II | Placebo comparator | 20 mg Saline infused slowly over 20 minutes. Placebo 1 capsule Day 1, 2 capsules Day 2, 3 capsules Day 3, 4 capsules days 4 to 30; 3 capsules Day 31 to 33; 2 capsules day 34 to 36 and 1 capsule 37 to 39. Receives: Drug: Flumazenil and Gabapentin; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Subjects Completely Abstinent
percent of subjects completely abstinent during the six week medication study study
Measured: 6 week trial
Percent Days Abstinent
percent days abstinent during treatment
Measured: Weeks 1 to 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2005 (estimated)
- Study startDec 2005
- Primary completionFeb 2008
- Study completionMar 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Alcohol DependenceStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Raymond F. Anton, Medical University of South Carolina
- Investigators
- Raymond F Anton, MD, Principal investigator, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00262639
- Sponsor's protocol ID
- 15844
- Status last verified
- Feb 2019
- First submitted
- 5 Dec 2005
- Last updated
- 15 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Anton RF, Myrick H, Baros AM, Latham PK, Randall PK, Wright TM, Stewart SH, Waid R, Malcolm R. Efficacy of a combination of flumazenil and gabapentin in the treatment of alcohol dependence: relationship to alcohol withdrawal symptoms. J Clin Psychopharmacol. 2009 Aug;29(4):334-42. doi: 10.1097/JCP.0b013e3181aba6a4.
PubMed 19593171Schacht JP, Randall PK, Waid LR, Baros AM, Latham PK, Wright TM, Myrick H, Anton RF. Neurocognitive performance, alcohol withdrawal, and effects of a combination of flumazenil and gabapentin in alcohol dependence. Alcohol Clin Exp Res. 2011 Nov;35(11):2030-8. doi: 10.1111/j.1530-0277.2011.01554.x. Epub 2011 Jun 1.
PubMed 21631542
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double Blind Evaluation of Flumazenil and Gabapentin for the Treatment of Alcohol Withdrawal and Relapse Prevention
- ClinicalTrials.gov ID
- NCT00262639
- Acronym / sponsor ID
- 15844
- Conditions
- Alcohol Dependence
- Keywords
- Alcoholism, Alcohol Dependence, Alcohol Withdrawal, Treatment, Pharmacotherapy
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Study start
- Dec 2005
- Primary completion
- Feb 2008 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 7 Dec 2005 (estimated)
- Results
- Posted 14 Aug 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a placebo controlled trial (some people receive active and some people receive inactive medication) to evaluate the effectiveness of a new protocol to treat alcohol dependence. Two main medications (plus ancillary non-placebo controlled medications) and their placebos (inactive drugs) will be utilized to treat both alcohol withdrawal, promote abstinence, and reduce drinking over approximately a six-week treatment period. All participants will meet criteria for Alcohol Dependence and be drinking heavily up until 72 hours prior to receiving the first study drug. They will be injected one drug (flumazenil or placebo) over a two day period and receive the second one (gabapentin or placebo) by mouth for 39 days. The main hypothesis is that this protocol will reduce early alcohol withdrawal symptoms and will reduce relapse to drinking and promote abstinence compared to the placebo (inactive) drug group. Secondary outcomes that will be evaluated include reduction in craving, improvement in sleep, brain activity and mood.
Detailed description
Approximately 60 alcohol dependent individuals who are drinking heavily up until 72 hours, or less, prior to study participation will be randomized to receive either flumazenil (intravenously)on two successive days and gabapentin (orally)for 39 days or their matching placebos. They also will receive hydroxyzine and vitamins. Individuals will be evaluated for alcohol withdrawal, their response to acoustic startle, cognitive ability, craving, mood, sleep and drinking during the first week. They will then be seen weekly for about 6 weeks during which they take gabapentin or placebo and are provided with Combined Behavioral Intervention Therapy (counseling) once a week, or more, as required. Over this period they will be evaluated weekly for alcohol consumption, craving, sleep, mood, and biological markers of alcohol consumption ( percent carbohydrate deficient transferrin and gamma-glutamyl transferase). Blood will be obtained on week 3 and 6 for general health (liver, blood count etc.) screening. After the end of treatment, subjects will be followed-up at 4 weeks and again at 8 weeks after treatment to evaluate alcohol consumption, craving, sleep, mood.
Subjects will undergo a functional magnetic resonance imaging (MRI) procedure sometime during the second or third week of study medication to assess cue induced regional brain activation to investigate the effect of medication on brain response to alcohol visual cues.
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 |
|---|---|---|
| I | Experimental | Drug: Flumazenil and Gabapentin2 mg flumazenil given over 20 minutes on Day 1 and Day 2. Gabapentin 300 mg Day 1; gabapentin 600 mg Day 2; gabapentin 900 mg Day 3; gabapentin 1200 mg Day 4 to 30; gabapentin 900 mg day 31-33; gabapentin 600 mg day 34-36; gabapentin 300 mg day 37-39. |
| II | Placebo comparator | Drug: Flumazenil and Gabapentin, Drug: Placebo20 mg Saline infused slowly over 20 minutes. Placebo 1 capsule Day 1, 2 capsules Day 2, 3 capsules Day 3, 4 capsules days 4 to 30; 3 capsules Day 31 to 33; 2 capsules day 34 to 36 and 1 capsule 37 to 39. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age 18 - 70.
- Participants will meet criteria for primary DSM IV alcohol dependence, drink on at least 70% of days in the last 30 days prior to assessment, and drink at least 5 drinks per drinking day.
- No more than 72 hours since last drink of alcohol. Rationale: to focus on symptoms occurring during the early alcohol cessation period.
- Low CIWA-Ar group: have a CIWA-Ar score less than or equal to 6; High CIWA-Ar group: have a CIWA-Ar score greater than or equal to 7 but less than or equal to 15.
- Able to read and understand questionnaires and informed consent.
Key exclusion criteria (15 listed)
- Currently meets DSM-IV criteria for any other psychoactive substance dependence disorder except nicotine dependence.
- Any psychoactive substance abuse, except marijuana and nicotine, within the last 30 days as evidenced by subject report or urine drug screen.
- Meets DSM-IV criteria for current axis I disorders of major depression, panic disorder, obsessive-compulsive disorder, generalized anxiety disorder, post-traumatic stress syndrome, bipolar affective disorder, schizophrenia, or any other psychotic disorder or organic mental disorder. The rationale for excluding them is that symptoms from these disorders may affect dependent variables and complicate interpretation of the data.
- No use of benzodiazepines in excess of three times in the past two weeks by self report and urine drug screen.
- Subjects must not be taking zolpidem (Ambien™), zaleplon (Sonata™), or eszopiclone (Lunesta™) in excess of three times in past two weeks.
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 |
|---|---|---|
| Flumazenil and Gabapentin2 mg flumazenil for infusion given slowly over 20 minutes given day 1 and day 2 gabapentin 300 mg increasing to 1200 mg over 4 days and continuing to day 30. Gabapentin 900 mg Day 31 to Day 33 gabapentin 600 mg Day 34 to 36 and gabapentin 300 mg Day 37 to 39. | Drug | I, II |
| Placebo20 mg Saline infused slowly over 20 minutes. Placebo 1 capsule Day 1, 2 capsules Day 2, 3 capsules Day 3, 4 capsules days 4 to 30; 3 capsules Day 31 to 33; 2 capsules day 34 to 36 and 1 capsule 37 to 39. | Drug | II |
Primary outcome
Percent Subjects Completely Abstinent
Time frame: 6 week trial
percent of subjects completely abstinent during the six week medication study study
Percent Days Abstinent
Time frame: Weeks 1 to 6
percent days abstinent during treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19593171Anton RF, Myrick H, Baros AM, Latham PK, Randall PK, Wright TM, Stewart SH, Waid R, Malcolm R. Efficacy of a combination of flumazenil and gabapentin in the treatment of alcohol dependence: relationship to alcohol withdrawal symptoms. J Clin Psychopharmacol. 2009 Aug;29(4):334-42. doi: 10.1097/JCP.0b013e3181aba6a4.
- Results publication: PubMed 21631542Schacht JP, Randall PK, Waid LR, Baros AM, Latham PK, Wright TM, Myrick H, Anton RF. Neurocognitive performance, alcohol withdrawal, and effects of a combination of flumazenil and gabapentin in alcohol dependence. Alcohol Clin Exp Res. 2011 Nov;35(11):2030-8. doi: 10.1111/j.1530-0277.2011.01554.x. Epub 2011 Jun 1.
- Main Web Page for the MUSC-Center for Drug and Alcohol ProgramsLink provided by the sponsor.
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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.
Raymond F Anton, MD principal investigator
Medical University of South Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Flumazenil and Gabapentin in people with Alcohol Dependence, run by Medical University of South Carolina at 1 site in United States.
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 6 inclusion and 15 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 15 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Aug 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percent Subjects Completely Abstinent (time frame: 6 week trial). The study lists 2 primary outcomes in all. 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 NCT00262639, 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 15 Feb 2019.