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

• ClinicalTrials.gov Identifier: NCT00817089
• Recruitment Status: Completed
• First Posted: January 6, 2009
• Results First Posted: November 21, 2019
• Last Update Posted: November 21, 2019
• Sponsor: University of Pennsylvania
• Information provided by (Responsible Party): David Oslin, University of Pennsylvania

Study Description

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 consists of two inpatient alcohol challenge sessions with treatment using random assignment to either naltrexone or placebo.

Condition or disease	Intervention/treatment	Phase
Alcoholism	Drug: Placebo Oral Tablet; Drug: Naltrexone	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 subjects were admitted to the UPenn Translational Research Center and receive two alcohol challenge sessions after pretreatment with naltrexone or placebo.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Groups 1 and 3 get placebo in session 1 and placebo in session 2, Groups 2 and 4 get placebo in session 1 and naltrexone in session 2
• 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

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Group 1 Asn40 Placebo Placebo; Each alcohol session preceded by pretreatment with placebo oral tablet	Drug: Placebo Oral Tablet; Placebo pill; Other Name: Placebo
Active Comparator: Group 2 Asn40 Placebo Naltrexone; The first alcohol session preceded by pretreatment with placebo oral tablet. The second alcohol session preceded by pretreatment with naltrexone 50 mg as a single dose.	Drug: Placebo Oral Tablet; Placebo pill; Other Name: Placebo; Drug: Naltrexone; 50 mg of naltrexone prior to challenge session
Placebo Comparator: Group 3 Asp40 Placebo Placebo; Each alcohol session preceded by pretreatment with placebo oral tablet	Drug: Placebo Oral Tablet; Placebo pill; Other Name: Placebo
Active Comparator: Group 4 Asp40 Placebo Naltrexone; The first alcohol session preceded by pretreatment with placebo oral tablet. The second alcohol session preceded by pretreatment with naltrexone 50 mg as a single dose.	Drug: Placebo Oral Tablet; Placebo pill; Other Name: Placebo; Drug: Naltrexone; 50 mg of naltrexone prior to challenge session

Outcome Measures

Primary Outcome Measures :

1. Biphasic Alcohol Effects Scale:Total Mood [ Time Frame: during 2nd alcohol challenge session ]

   Change from baseline to peak cortisol response, during the 2nd alcohol challenge session, subjective response as measured by Biphasic Alcohol Effects Scale: Total Mood.

   Biphasic Alcohol Effects Scale: Total Mood: minimum = 0, maximum = 106, higher scores indicate better outcomes.

Secondary Outcome Measures :

1. Adrenocorticotropic Hormone (ACTH) Levels [ Time Frame: during 2nd alcohol challenge session ]
   Change from baseline to peak cortisol response during the 2nd alcohol challenge session, objective response as measured by Adrenocorticotropic hormone (ACTH).

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

University of Pennsylvania

Investigators

• Principal Investigator: David Oslin, M.D.; University of Pennsylvania

More Information

• Responsible Party: David Oslin, Professor, University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT00817089
• Other Study ID Numbers: 806019
• First Posted: January 6, 2009
• Results First Posted: November 21, 2019
• Last Update Posted: November 21, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Alcoholism; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Naltrexone; Alcohol Deterrents; Narcotic Antagonists; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents