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

Alcohol Dependence Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00570388
• Other study ID #: 20062166
• Secondary ID: WIRB Protocol Nu
• Status: Recruiting
• Phase: N/A
• First received: December 6, 2007
• Last updated: January 15, 2008
• Start date: March 2007
• Est. completion date: September 2008

Study information

• Verified date: January 2008
• Source: Institute of Addiction Medicine
• Contact: Jenny J Starosta, PhD
• Phone: 215-248-6025
• Email: 2evolve[@]gmail.com
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alcohol Dependence
• Alcoholism

Intervention

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.

Locations

Country	Name	City	State
United States	Institute of Addiction Medicine	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Addiction Medicine

Country where clinical trial is conducted

United States, 

References & Publications (13)

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. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2006 Mar 20. — View Citation

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

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. — View Citation

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. — View Citation

Singh N, Sharma A, Singh M. Possible mechanism of alprazolam-induced amnesia in mice. Pharmacology. 1998 Jan;56(1):46-50. — View Citation

Srisurapanont M, Jarusuraisin N. Opioid antagonists for alcohol dependence. Cochrane Database Syst Rev. 2005 Jan 25;(1):CD001867. Review. Update in: Cochrane Database Syst Rev. 2010;(12):CD001867. — View Citation

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

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. — View Citation

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

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

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No