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

NCT ID: NCT00570388

Last Updated: 2008-01-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-03-31

Study Completion Date

2008-09-30

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.

Conditions

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Alcohol Dependence

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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2

Subjects in the active Prometa group will receive flumazenil, gabapentin, and hydroxyzine per the Prometa Protocol.

Group Type ACTIVE_COMPARATOR

Prometa Treatment Program

Intervention Type DRUG

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.

1

Subjects in the "placebo group" will receive placebo flumazenil, gabapentin, and hydroxyzine

Group Type PLACEBO_COMPARATOR

Prometa Treatment Program

Intervention Type DRUG

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.

Interventions

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Prometa Treatment Program

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.

Intervention Type DRUG

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Institute of Addiction Medicine

OTHER

Sponsor Role lead

Responsible Party

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Institute of Addiction Medicine

Principal Investigators

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Jenny J Starosta, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute of Addiction Medicine

Joseph Volpicelli, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute of Addiction Medicine

Locations

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Institute of Addiction Medicine

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Jenny J Starosta, PhD

Role: CONTACT

215-248-6025

Joseph Volpicelli, MD, PhD

Role: CONTACT

215-248-6025

Facility Contacts

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Jenny J Starosta, PhD

Role: primary

215-248-6025

Joseph Volpicelli, MD, PhD

Role: backup

215-248-6025

References

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Matching alcoholism treatments to client heterogeneity: treatment main effects and matching effects on drinking during treatment. Project MATCH Research Group. J Stud Alcohol. 1998 Nov;59(6):631-9. doi: 10.15288/jsa.1998.59.631.

Reference Type BACKGROUND
PMID: 9811084 (View on PubMed)

Barker MJ, Greenwood KM, Jackson M, Crowe SF. Cognitive effects of long-term benzodiazepine use: a meta-analysis. CNS Drugs. 2004;18(1):37-48. doi: 10.2165/00023210-200418010-00004.

Reference Type BACKGROUND
PMID: 14731058 (View on PubMed)

Bates ME, Pawlak AP, Tonigan JS, Buckman JF. Cognitive impairment influences drinking outcome by altering therapeutic mechanisms of change. Psychol Addict Behav. 2006 Sep;20(3):241-53. doi: 10.1037/0893-164X.20.3.241.

Reference Type BACKGROUND
PMID: 16938062 (View on PubMed)

Girdler NM, Lyne JP, Wallace R, Neave N, Scholey A, Wesnes KA, Herman C. A randomised, controlled trial of cognitive and psychomotor recovery from midazolam sedation following reversal with oral flumazenil. Anaesthesia. 2002 Sep;57(9):868-76. doi: 10.1046/j.1365-2044.2002.02785.x.

Reference Type BACKGROUND
PMID: 12190751 (View on PubMed)

Mason BJ. Treatment of alcohol-dependent outpatients with acamprosate: a clinical review. J Clin Psychiatry. 2001;62 Suppl 20:42-8.

Reference Type BACKGROUND
PMID: 11584875 (View on PubMed)

Mason BJ, Goodman AM, Chabac S, Lehert P. Effect of oral acamprosate on abstinence in patients with alcohol dependence in a double-blind, placebo-controlled trial: the role of patient motivation. J Psychiatr Res. 2006 Aug;40(5):383-93. doi: 10.1016/j.jpsychires.2006.02.002. Epub 2006 Mar 20.

Reference Type BACKGROUND
PMID: 16546214 (View on PubMed)

Rupp CI, Fleischhacker WW, Drexler A, Hausmann A, Hinterhuber H, Kurz M. Executive function and memory in relation to olfactory deficits in alcohol-dependent patients. Alcohol Clin Exp Res. 2006 Aug;30(8):1355-62. doi: 10.1111/j.1530-0277.2006.00162.x.

Reference Type BACKGROUND
PMID: 16899038 (View on PubMed)

Singh N, Sharma A, Singh M. Possible mechanism of alprazolam-induced amnesia in mice. Pharmacology. 1998 Jan;56(1):46-50. doi: 10.1159/000028181.

Reference Type BACKGROUND
PMID: 9467187 (View on PubMed)

Srisurapanont M, Jarusuraisin N. Opioid antagonists for alcohol dependence. Cochrane Database Syst Rev. 2005 Jan 25;(1):CD001867. doi: 10.1002/14651858.CD001867.pub2.

Reference Type BACKGROUND
PMID: 15674887 (View on PubMed)

Stewart SA. The effects of benzodiazepines on cognition. J Clin Psychiatry. 2005;66 Suppl 2:9-13.

Reference Type BACKGROUND
PMID: 15762814 (View on PubMed)

Tapert SF, Ozyurt SS, Myers MG, Brown SA. Neurocognitive ability in adults coping with alcohol and drug relapse temptations. Am J Drug Alcohol Abuse. 2004 May;30(2):445-60. doi: 10.1081/ada-120037387.

Reference Type BACKGROUND
PMID: 15230085 (View on PubMed)

Uekermann J, Daum I, Schlebusch P, Wiebel B, Trenckmann U. Depression and cognitive functioning in alcoholism. Addiction. 2003 Nov;98(11):1521-9. doi: 10.1046/j.1360-0443.2003.00526.x.

Reference Type BACKGROUND
PMID: 14616178 (View on PubMed)

Zinn S, Stein R, Swartzwelder HS. Executive functioning early in abstinence from alcohol. Alcohol Clin Exp Res. 2004 Sep;28(9):1338-46. doi: 10.1097/01.alc.0000139814.81811.62.

Reference Type BACKGROUND
PMID: 15365304 (View on PubMed)

Other Identifiers

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WIRB Protocol Number: 20062166

Identifier Type: -

Identifier Source: secondary_id

WIRB Study Number: 1085483

Identifier Type: -

Identifier Source: secondary_id

WIRB Invest. Number: 128549

Identifier Type: -

Identifier Source: secondary_id

20062166

Identifier Type: -

Identifier Source: org_study_id

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