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

Primary Purpose

Alcoholism

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Placebo Oral Tablet

Naltrexone

About this trial

This is an interventional treatment trial for Alcoholism

Eligibility Criteria

21 Years - 64 Years (Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

Males 21 years of age or older of European or Asian decent.
Has a current DSM IV diagnosis of alcohol dependence as determined by the Structural Clinical Interview for DSM IV (SCID-IV Mini).
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).
Has adequate vision, hearing, and ability to communicate to allow study participation.
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.
Has signed a witnessed informed consent
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:

Meets DSM-IV criteria for dependence on any substance other than alcohol or nicotine in the last 6 months.
Tests positive on the urine drug screen for opioids, cocaine, or amphetamine at the screening visit (only 1 repeat test permitted).
Meets current or lifetime DSM-IV criteria for bipolar affective disorder, schizophrenia, or any psychotic disorder
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
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)
Over age 64 and has evidence of severe cognitive impairment as evidenced by a Mini-mental status exam (MMSE) score <24
Has suicidal or homicidal ideation necessitating inpatient hospitalization
Has been abstinent more than 14 days prior to Phase 1
Is of African Descent
Meets current DSM-IV criteria for for major depression (non-substance induced), PTSD, or panic disorder.
Has significant hematological, pulmonary, endocrine, cardiovascular, renal, or gastrointestinal disease.

Sites / Locations

University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Active Comparator

Placebo Comparator

Active Comparator

Arm Label

Group 1 Asn40 Placebo Placebo

Group 2 Asn40 Placebo Naltrexone

Group 3 Asp40 Placebo Placebo

Group 4 Asp40 Placebo Naltrexone

Arm Description

Each alcohol session preceded by pretreatment with placebo oral tablet

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.

Each alcohol session preceded by pretreatment with placebo oral tablet

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.

Outcomes

Primary Outcome Measures

Biphasic Alcohol Effects Scale:Total Mood

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

Adrenocorticotropic Hormone (ACTH) Levels

Change from baseline to peak cortisol response during the 2nd alcohol challenge session, objective response as measured by Adrenocorticotropic hormone (ACTH).

Full Information

NCT ID

NCT00817089

First Posted

January 5, 2009

Last Updated

October 28, 2019

Sponsor

University of Pennsylvania

1. Study Identification

Unique Protocol Identification Number

NCT00817089

Brief Title

Understanding Treatment Response With Naltrexone Among White Alcoholics

Acronym

DEFINE II

Official Title

Defining an Endopheneotype for Alcohol Treatment With Naltrexone

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Completed

Study Start Date

December 2007 (undefined)

Primary Completion Date

April 2010 (Actual)

Study Completion Date

June 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Pennsylvania

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alcoholism

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

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

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1 Asn40 Placebo Placebo

Arm Type

Placebo Comparator

Arm Description

Each alcohol session preceded by pretreatment with placebo oral tablet

Arm Title

Group 2 Asn40 Placebo Naltrexone

Arm Type

Active Comparator

Arm Description

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.

Arm Title

Group 3 Asp40 Placebo Placebo

Arm Type

Placebo Comparator

Arm Description

Each alcohol session preceded by pretreatment with placebo oral tablet

Arm Title

Group 4 Asp40 Placebo Naltrexone

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo Oral Tablet

Other Intervention Name(s)

Placebo

Intervention Description

Placebo pill

Intervention Type

Drug

Intervention Name(s)

Naltrexone

Intervention Description

50 mg of naltrexone prior to challenge session

Primary Outcome Measure Information:

Title

Biphasic Alcohol Effects Scale:Total Mood

Description

Time Frame

during 2nd alcohol challenge session

Secondary Outcome Measure Information:

Title

Adrenocorticotropic Hormone (ACTH) Levels

Description

Change from baseline to peak cortisol response during the 2nd alcohol challenge session, objective response as measured by Adrenocorticotropic hormone (ACTH).

Time Frame

during 2nd alcohol challenge session

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

64 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Males 21 years of age or older of European or Asian decent. Has a current DSM IV diagnosis of alcohol dependence as determined by the Structural Clinical Interview for DSM IV (SCID-IV Mini). 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). Has adequate vision, hearing, and ability to communicate to allow study participation. 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. Has signed a witnessed informed consent 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: Meets DSM-IV criteria for dependence on any substance other than alcohol or nicotine in the last 6 months. Tests positive on the urine drug screen for opioids, cocaine, or amphetamine at the screening visit (only 1 repeat test permitted). Meets current or lifetime DSM-IV criteria for bipolar affective disorder, schizophrenia, or any psychotic disorder 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 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) Over age 64 and has evidence of severe cognitive impairment as evidenced by a Mini-mental status exam (MMSE) score <24 Has suicidal or homicidal ideation necessitating inpatient hospitalization Has been abstinent more than 14 days prior to Phase 1 Is of African Descent Meets current DSM-IV criteria for for major depression (non-substance induced), PTSD, or panic disorder. Has significant hematological, pulmonary, endocrine, cardiovascular, renal, or gastrointestinal disease.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David Oslin, M.D.

Organizational Affiliation

University of Pennsylvania

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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Understanding Treatment Response With Naltrexone Among White Alcoholics

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