Neurocognitive Functioning Following The PROMETA® Treatment Protocol In Subjects With Alcohol Dependence - Full Text View

Sponsor:	Institute of Addiction Medicine
Information provided by:	Institute of Addiction Medicine
ClinicalTrials.gov Identifier:	NCT00570388

Purpose

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.

Condition	Intervention
Alcohol Dependence	Drug: Prometa Treatment Program

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Neurocognitive Functioning Following The PROMETA® Treatment Protocol In Subjects With Alcohol Dependence

Resource links provided by NLM:

MedlinePlus related topics: Alcoholism

Drug Information available for: Ethanol

U.S. FDA Resources

Further study details as provided by Institute of Addiction Medicine:

Primary Outcome Measures:

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: Time Frame: Eight Weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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. [ Time Frame: Eight Weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	120
Study Start Date:	March 2007
Estimated Study Completion Date:	September 2008

Arms	Assigned Interventions
2: Active Comparator Subjects in the active Prometa group will receive flumazenil, gabapentin, and hydroxyzine per the Prometa Protocol.	Drug: 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.
1: Placebo Comparator Subjects in the "placebo group" will receive placebo flumazenil, gabapentin, and hydroxyzine	Drug: 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.

Arms

Assigned Interventions

2: Active Comparator

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

Drug: 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.

1: Placebo Comparator

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

Drug: 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.

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00570388

Contacts

Contact: Jenny J Starosta, PhD	215-248-6025	2evolve@gmail.com
Contact: Joseph Volpicelli, MD, PhD	215-248-6025	volpj@aol.com

Locations

United States, Pennsylvania
Institute of Addiction Medicine	Recruiting
Philadelphia, Pennsylvania, United States, 19118
Contact: Jenny J Starosta, PhD 215-248-6025 2evolve@gmail.com
Contact: Joseph Volpicelli, MD, PhD 215-248-6025 volpj@aol.com
Principal Investigator: Jenny J Starosta, PhD
Principal Investigator: Joseph Volpicelli, MD, PhD

Sponsors and Collaborators

Institute of Addiction Medicine

Investigators

Principal Investigator:	Jenny J Starosta, PhD	Institute of Addiction Medicine
Principal Investigator:	Joseph Volpicelli, MD, PhD	Institute of Addiction Medicine

More Information

Publications:

[No authors listed] 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.

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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.

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

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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.

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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.

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

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

Responsible Party:	Institute of Addiction Medicine ( Jenny Starosta, Ph.D. and Joseph Volpicelli, MD, PhD- Co-Principal Investigator )
Study ID Numbers:	20062166, WIRB Protocol Number: 20062166, WIRB Study Number: 1085483, WIRB Invest. Number: 128549
Study First Received:	December 6, 2007
Last Updated:	January 15, 2008
ClinicalTrials.gov Identifier:	NCT00570388 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Institute of Addiction Medicine:

Neurocognitive
Alcohol Dependence
Prometa
Prometa Protocol
Starosta

Additional relevant MeSH terms:

Mental Disorders
Alcoholism
Substance-Related Disorders
Disorders of Environmental Origin
Alcohol-Related Disorders

ClinicalTrials.gov processed this record on February 08, 2010