Neurocognitive Functioning Following The PROMETA® Treatment Protocol In Subjects With Alcohol Dependence

Study Overview
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Brief Summary
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This study will test the safety and efficacy of the PROMETA® Treatment Protocol (which includes the benzodiazepine antagonist flumazenil) in reversing the neurocognitive impairment and this in turn will lead to improved ability to resist alcohol related cues and enhance involvement in psychosocial treatment.

Detailed Description
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The principal aim of this study is to extend our evaluation of the PROMETA® Treatment Protocol as a means to improve neurocognitive functioning in recently detoxified alcohol dependent subjects. For many alcohol dependent patients entering treatment, a range of neurocognitive deficits are present that not only had adverse effects on the patient's ability to function and think clearly but these deficits also impair the process of addiction treatment. For example, alcohol dependent subjects typically experience high levels of alcohol craving in the early stages of treatment. The patient is left with the choice of relieving craving by drinking alcohol to provide immediate relief of craving symptoms or abstaining from alcohol to obtain long-term benefits from recovery of the complications from excessive drinking. We have previously shown in open label trials that the PROMETA® Treatment Protocol helps stimulant abusers in the early stages of recovery, have relatively low rates of relapse to stimulant use. It is not clear if the Protocol is effective because of less urges to use stimulants or the ability to resist these urges is improved from a recovery of Neurocognitive functioning. The present proposal extends our previous research by comparing the efficacy of the PROMETA® Treatment Protocol in a double blind placebo controlled trial using a new population of substance abusers (alcohol dependent subjects) and assessing the effects of the PROMETA® Treatment Protocol on neurocognitive functioning, particularly those aspects of functioning that affect the ability to make decisions that have important long-term benefits.

Official Title
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Neurocognitive Functioning Following The PROMETA® Treatment Protocol In Subjects With Alcohol Dependence

Conditions
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Alcohol Dependence

Intervention / Treatment
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* Drug: Prometa Treatment Program


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must meet DSM-IV criteria for current diagnosis of alcohol dependence. In the past 30 days, patient had an average of >15 standard alcohol drinks/week with at least one day of five or more drinks. Patient must have successfully completed detoxification from alcohol (abstinent for three consecutive days). As evidenced by self-report or three negative breathalyzer reading and a CIWA-Ar score less than 6. Patient understands and signs the consent. Exclusion Criteria: Patients with a current DSM-IV diagnosis of any substance dependence other than alcohol, nicotine, or cannabis. Patients with a current or past history of DSM-IV diagnosis of Panic Disorder Evidence of benzodiazepine use in the past 15 days, determined by self-report and/or by a urine drug screen Patients with a seizure disorder being managed with a benzodiazepine or for whom a benzodiazepine is being considered Patients who are currently being treated with psychotropic medications, including disulfiram, naltrexone, or acamprosate at the time of study entry. Patients with a history of unstable or serious medical illness, including need for benzodiazepines. Known severe physical or medical illnesses such as AIDS, active hepatitis, Current severe psychiatric symptoms, e.g., psychosis, dementia, acute suicidal or homicidal ideation, mania or depression requiring newly initiated antidepressant or psychotropic therapy, or which would make it unsafe for the patient to participate in the opinion of the primary investigator. Patients who have used investigational medication in the past 30 days. Female patients who are pregnant, nursing, or not using a reliable method of contraception. Patients with a condition that would make intravenous administration of medications difficult (e.g. absence of suitable peripheral veins). Have a known or hypersensitivity to medication components of PROMETA®TM Have been treated with PROMETA® for any reason currently or in the past year

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 2<br>Subjects in the active Prometa group will receive flumazenil, gabapentin, and hydroxyzine per the Prometa Protocol. | Drug: Prometa Treatment Program<br>* Day 1-3•Hydroxyzine HCL 50 mg and multivitamins with minerals po one hour before flumazenil infusion. Flumazenil infusion. Day 1•Gabapentin 300 mg po 9PM w/ hydroxyzine HCL 50 mg PRN for sleep. Day 2•Gabapentin 600 mg po 9PM w/ hydroxyzine HCL 50 mg PRN Day 3•Gabapentin 900 mg po 9PM w/ hydroxyzine HCL 50 mg PRN Days 4 through 28•Gabapentin 1200 mg po 9 PM Days 29 through 31•Gabapentin 900 mg po 9 PM Days 32 through 34•Gabapentin 600 mg po 9 PM Days 35 through 38•Gabapentin 300 mg po 9 PM Flumazenil Dosing Schedule 2 mg flumazenil is given as a slow IV push. Subjects in the placebo group will receive placebo flumazenil, gabapentin, and hydroxyzine; subjects in the active group will receive flumazenil, gabapentin, and hydroxyzine per protocol.<br>|
| Placebo Comparator: 1<br>Subjects in the placebo group will receive placebo flumazenil, gabapentin, and hydroxyzine | Drug: Prometa Treatment Program<br>* Day 1-3•Hydroxyzine HCL 50 mg and multivitamins with minerals po one hour before flumazenil infusion. Flumazenil infusion. Day 1•Gabapentin 300 mg po 9PM w/ hydroxyzine HCL 50 mg PRN for sleep. Day 2•Gabapentin 600 mg po 9PM w/ hydroxyzine HCL 50 mg PRN Day 3•Gabapentin 900 mg po 9PM w/ hydroxyzine HCL 50 mg PRN Days 4 through 28•Gabapentin 1200 mg po 9 PM Days 29 through 31•Gabapentin 900 mg po 9 PM Days 32 through 34•Gabapentin 600 mg po 9 PM Days 35 through 38•Gabapentin 300 mg po 9 PM Flumazenil Dosing Schedule 2 mg flumazenil is given as a slow IV push. Subjects in the placebo group will receive placebo flumazenil, gabapentin, and hydroxyzine; subjects in the active group will receive flumazenil, gabapentin, and hydroxyzine per protocol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome measure is neurocognitive functioning as assessed by a battery of standardized neurocognitive tests that assess, executive functioning, verbal memory, general intelligence, and attention. |  | Time Frame: Eight Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary outcome measures include, alcohol craving, subject retention, percent of abstinent days, percent of heavy drinking days, time to first heavy drinking day, and blood chemistries including liver enzymes, reports of side effects. |  | Eight Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neurocognitive, Alcohol Dependence, Prometa, Prometa Protocol, Starosta