Prometa Protocol for Alcohol Dependence
| Status: | Completed |
|---|---|
| Conditions: | Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - 70 |
| Updated: | 2/17/2019 |
| Start Date: | December 2005 |
| End Date: | March 2008 |
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.
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.
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.
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.
Inclusion Criteria:
1. Age 18 - 70.
2. 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.
3. No more than 72 hours since last drink of alcohol. Rationale: to focus on symptoms
occurring during the early alcohol cessation period.
4. 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.
5. Able to read and understand questionnaires and informed consent.
6. Has stable housing for past 3 months.
Exclusion Criteria:
1. Currently meets DSM-IV criteria for any other psychoactive substance dependence
disorder except nicotine dependence.
2. Any psychoactive substance abuse, except marijuana and nicotine, within the last 30
days as evidenced by subject report or urine drug screen.
3. 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.
4. No use of benzodiazepines in excess of three times in the past two weeks by self
report and urine drug screen.
5. Subjects must not be taking zolpidem (Ambien™), zaleplon (Sonata™), or eszopiclone
(Lunesta™) in excess of three times in past two weeks.
6. No history of delirium tremens or alcohol withdrawal seizures.
7. Has current suicidal ideation with plan or homicidal ideation.
8. Need for maintenance or acute treatment with any psychoactive medication including
antiseizure medications.
9. Use of disulfiram, naltrexone, acamprosate, or anticonvulsants in last 30 days.
10. Clinically significant medical problems such as cardiovascular, renal, GI, or
endocrine problem that would impair participation or limit medication ingestion.
11. 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.
12. Has current charges pending for a violent crime (not including DUI related offenses).
13. Has taken gabapentin or flumazenil in the last month or has experienced adverse
effects from it at any time in the past.
14. Hepatocellular disease indicated by elevations of SGPT (ALT) and SGOT (AST) greater
than 3 times normal at screening.
15. Persons with metal implants or pacemaker since fMRI will be used.
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