Understanding Treatment Response With Naltrexone Among White Alcoholics (DEFINE II)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00817089
Recruitment Status : Completed
First Posted : January 6, 2009
Last Update Posted : August 5, 2011
Information provided by:
University of Pennsylvania

Brief Summary:
This is a study involving treatment for alcohol dependence among males of European or Asian decent. The ultimate aim of this line of investigation is to further establish a genetic link between alcohol dependence and treatment by defining an endophenotype associated with treatment response. The study will combine two inpatient alcohol challenge sessions along with 12 weeks of outpatient treatment using random assignment to either naltrexone or placebo.

Condition or disease Intervention/treatment Phase
Alcoholism Drug: naltrexone Drug: placebo Other: alcohol Phase 4

Detailed Description:

Despite the well-established efficacy of naltrexone, there are significant variations in individual responses to naltrexone. A critical question remains: under what circumstances and for which patients will naltrexone be most beneficial? Recent work at our center provides evidence that the mu-opioid receptor (OPRM1) gene polymorphism A118G (Asn40Asp) imparts a significant change in treatment response. We have shown that patients with Asn40 variant (absence of heavy drinking -73.9% v/s 49% response). To further consolidate our knowledge, we wish to test the relationship between A118G polymorphism and the subjective/objective measures to alcohol among alcoholics treated with naltrexone. This work is focused on subjects of European or Asian decent as the A118G polymorphism occurs in less than 1% of those of African decent.

Up to 40 subjects will be recruited. The study is divided into two phases. For the first phase (Phase I) subjects are admitted to the UPenn Translational Research Center and receive two alcohol challenge sessions after pretreatment with naltrexone or placebo. Phase II continues with 12 weeks of outpatient treatment, immediately following the sessions, after random assignment to naltrexone or placebo.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Defining an Endopheneotype for Alcohol Treatment With Naltrexone
Study Start Date : December 2007
Actual Primary Completion Date : April 2010
Actual Study Completion Date : June 2010

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: P1A
Phase 1: Placebo then naltrexone prior to alcohol challenge sessions
Drug: naltrexone
phase 1: 30 or 50 mg of naltrexone prior to challenge session; phase 2: 50mg/day for 12 weeks
Other Name: ReVia

Other: alcohol
190 proof alcohol prepared to 11% volume mixed with fruit juice

Placebo Comparator: P1B
Phase 1: placebo prior to alcohol challenge sessions
Drug: placebo
placebo pills

Other: alcohol
190 proof alcohol prepared to 11% volume mixed with fruit juice

Experimental: P2A
Phase 2: naltrexone treatment
Drug: naltrexone
phase 1: 30 or 50 mg of naltrexone prior to challenge session; phase 2: 50mg/day for 12 weeks
Other Name: ReVia

Placebo Comparator: P2B
Phase 2: placebo
Drug: placebo
placebo pills

Primary Outcome Measures :
  1. Differences between the peak cortisol response (and subjective response) of all individuals including those with different genetic markers, during the naltrexone-alcohol session, subjective response as measured by Biphasic Alcohol Effects Scale. [ Time Frame: during challenge sessions ]

Secondary Outcome Measures :
  1. Improvement in quality of life (MOS SF-12), alternative drinking measures, biological markers of heavy drinking (CDT and GGT) [ Time Frame: 12 weeks ]
  2. Asp40 gene variant and family history of alcohol problems. [ Time Frame: once ]

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Ages Eligible for Study:   21 Years to 64 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Males 21 years of age or older of European or Asian decent.
  2. Has a current DSM IV diagnosis of alcohol dependence as determined by the Structural Clinical Interview for DSM IV (SCID-IV Mini).
  3. Drank an average of 21 drinks/week in the 60 days prior to treatment and had at least 2 occasions of heavy drinking (5 or more drinks on a given day for men), as measured by the Timeline Followback (TLFB).
  4. Has adequate vision, hearing, and ability to communicate to allow study participation.
  5. Successfully completes detoxification as manifested by at least 48 consecutive hours of no self-reported alcohol use immediately prior to admission to the inpatient unit.
  6. Has signed a witnessed informed consent
  7. Scores below an 8 on the Clinical Inventory of Withdrawal for Alcohol (CIWA) prior to starting naltrexone/placebo; and 8) Can speak, print, and understand English.

Exclusion Criteria:

  1. Meets DSM-IV criteria for dependence on any substance other than alcohol or nicotine in the last 6 months.
  2. Tests positive on the urine drug screen for opioids, cocaine, or amphetamine at the screening visit (only 1 repeat test permitted).
  3. Meets current or lifetime DSM-IV criteria for bipolar affective disorder, schizophrenia, or any psychotic disorder
  4. The presence of unstable or serious medical illness, including history of stroke, seizure disorder, severe liver disease (AST or ALT > 5x normal at the time of randomization), or unstable cardiac disease
  5. Has taken any psychotropic medications (including disulfiram) regularly within the last seven days prior to randomization (14 days for fluoxetine) or needs immediate treatment with a psychotropic medication (with the exception of detoxification medications or benadryl used sparingly for sleep)
  6. Over age 64 and has evidence of severe cognitive impairment as evidenced by a Mini-mental status exam (MMSE) score <24
  7. Has suicidal or homicidal ideation necessitating inpatient hospitalization
  8. Has been abstinent more than 14 days prior to Phase 1
  9. Is of African Descent
  10. Meets current DSM-IV criteria for for major depression (non-substance induced), PTSD, or panic disorder.
  11. Has significant hematological, pulmonary, endocrine, cardiovascular, renal, or gastrointestinal disease.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00817089

United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Principal Investigator: David Oslin, M.D. University of Pennsylvania

Responsible Party: David Oslin, M.D., University of Pennsylvania Identifier: NCT00817089     History of Changes
Other Study ID Numbers: 806019
First Posted: January 6, 2009    Key Record Dates
Last Update Posted: August 5, 2011
Last Verified: August 2011

Additional relevant MeSH terms:
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Anti-Infective Agents, Local
Anti-Infective Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Narcotic Antagonists
Sensory System Agents
Peripheral Nervous System Agents