DEFINE II: Understanding Treatment Response With Naltrexone Among White Alcoholics

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT00817089
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 4
• Duration (Months): 30
• Patients Per Site Per Month: 0.8

Study Details

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
• 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 2Groups 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: Dec 1, 2007
• Actual Primary Completion Date: Apr 1, 2010
• Actual Study Completion Date: Jun 1, 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 Names: 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 Names: 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 Names: 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 Names: Placebo ; Drug: Naltrexone; 50 mg of naltrexone prior to challenge session

Outcome Measures

Primary Outcome Measures

1. Biphasic Alcohol Effects Scale:Total Mood [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 [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

Criteria

• Ages Eligible for Study: 21 Years to 64 Years
• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: David Oslin, Professor, University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT00817089
• Other Study ID Numbers: 806019
• First Posted: Jan 6, 2009
• Last Update Posted: Nov 21, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Alcoholism; Naltrexone

Study Results

Participant Flow

Arm/Group Title	Group 1: Asn40 Placebo Placebo	Group 2: Asn40 Placebo Naltrexone	Group 3: Asp40 Placebo Placebo	Group 4: Asp40 Placebo Naltrexone
Arm/Group Description	Asn40: Placebo, Placebo Each alcohol session preceded by pretreatment with placebo. Placebo: placebo pills alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice	Asn40: Placebo, Naltrexone The first alcohol challenge session preceded by pretreatment with placebo. The second alcohol challenge session preceded by pretreatment with naltrexone 50 mg as a single dose. Placebo: placebo pills naltrexone: 50 mg of naltrexone prior to challenge session alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice	Asp40: Placebo, Placebo Each alcohol challenge session preceded by pretreatment with placebo. Placebo: placebo pills alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice	Asp40: Placebo, Naltrexone The first alcohol challenge session preceded by pretreatment with placebo. The second challegne alcohol session preceded by pretreatment with naltrexone 50 mg as a single dose. Placebo: placebo pills naltrexone: 50 mg of naltrexone prior to challenge session alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice
Period Title: First Alcohol Challenge
STARTED	6	8	4	6
COMPLETED	6	8	4	5
NOT COMPLETED	0	0	0	1
Period Title: First Alcohol Challenge
STARTED	6	8	4	5
COMPLETED	6	7	4	5
NOT COMPLETED	0	1	0	0

Baseline Characteristics

Arm/Group Title	Group 1: Asn40 Placebo Placebo	Group 2: Asn40 Placebo Naltrexone	Group 3: Asp40 Placebo Placebo	Group 4: Asp40 Placebo Naltrexone	Total
Arm/Group Description	Asn40: Placebo, Placebo Each alcohol challenge session preceded by pretreatment with placebo Placebo: placebo pills alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice	Asn40: Placebo, Naltrexone The first alcohol challenge session preceded by pretreatment with placebo. The second challegne alcohol session preceded by pretreatment with naltrexone 50 mg as a single dose. Placebo: placebo pills naltrexone: 50 mg of naltrexone prior to challenge session alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice	Asp40: Placebo, Placebo Each alcohol challenge session preceded by pretreatment with placebo Placebo: placebo pills alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice	Asp40: Placebo, Naltrexone The first alcohol challenge session preceded by pretreatment with placebo. The second alcohol challenge session preceded by pretreatment with naltrexone 50 mg as a single dose. Placebo: placebo pills naltrexone: 50 mg of naltrexone prior to challenge session alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice	Total of all reporting groups
Overall Participants	6	8	4	6	24
Age, Customized (Count of Participants)
<21 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 21 and 65 years	6 100%	8 100%	4 100%	6 100%	24 100%
>65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%
Male	6 100%	8 100%	4 100%	6 100%	24 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
White	6 100%	8 100%	4 100%	6 100%	24 100%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Biphasic Alcohol Effects Scale:Total Mood
Description	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.
Time Frame	during 2nd alcohol challenge session

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1: Asn40 Placebo Placebo	Group 2: Asn40 Placebo Naltrexone	Group 3: Asp40 Placebo Placebo	Group 4: Asp40 Placebo Naltrexone
Arm/Group Description	Asn40: Placebo, Placebo Each alcohol challenge session preceded by pretreatment with placebo. Placebo: placebo pills alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice	Asn40: Placebo, Naltrexone The first alcohol challenge session preceded by pretreatment with placebo. The second alcohol challenge session preceded by pretreatment with naltrexone 50 mg as a single dose. Placebo: placebo pills naltrexone: 50 mg of naltrexone prior to challenge session alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice	Asp40: Placebo, Placebo Each alcohol challenge session preceded by pretreatment with placebo. Placebo: placebo pills alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice	Asp40: Placebo, Naltrexone The first alcohol challenge session preceded by pretreatment with placebo. The second alcohol challenge session preceded by pretreatment with naltrexone 50 mg as a single dose. Placebo: placebo pills naltrexone: 50 mg of naltrexone prior to challenge session alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice
Measure Participants	6	7	4	5
Mean (Standard Deviation) [units on a scale]	6.94 (9.53)	3.57 (18.46)	6.50 (4.04)	3.20 (8.11)

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1 Asn40 Placebo Placebo	Group 2 Asn40 Placebo Naltrexone	Group 3 Asp40 Placebo Placebo	Group 4 Asp40 Placebo Naltrexone
Arm/Group Description	Asn40: Placebo, Placebo Each alcohol challenge session preceded by pretreatment with placebo. Placebo: placebo pills alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice	Asn40: Placebo, Naltrexone The first alcohol challegne session preceded by pretreatment with placebo. The second alcohol challenge session preceded by pretreatment with naltrexone 50 mg as a single dose. Placebo: placebo pills Naltrexone: 50 mg of naltrexone prior to challenge session alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice	Asp40: Placebo, Placebo Each alcohol challenge session preceded by pretreatment with placebo oral tablet Placebo Oral Tablet: Placebo pill alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice	Asp40: Placebo, Naltrexone The first alcohol challenge session preceded by pretreatment with placebo oral tablet. The second alcohol challenge session preceded by pretreatment with naltrexone 50 mg as a single dose. Placebo Oral Tablet: Placebo pill Naltrexone: 50 mg of naltrexone prior to challenge session alcohol: 190 proof alcohol prepared to 11% volume mixed with fruit juice
Measure Participants	6	7	4	5
Mean (Standard Deviation) [pg/ml]	-7.83 (14.34)	3.86 (7.47)	5.25 (8.42)	-3.20 (14.10)

Adverse Events

Time Frame	36 hours
Adverse Event Reporting Description	Adverse events were tracked in the 36 hours after the second alcohol challenge session
Arm/Group Title	Group 1: Asn40 Placebo Placebo		Group 2: Asn40 Placebo Naltrexone		Group 3: Asp40 Placebo Placebo		Group 4: Asp40 Placebo Naltrexone
Arm/Group Description	Asn40: placebo, placebo Each alcohol challenge session preceded by pretreatment with placebo. placebo: placebo pills alcohol : 190 proof alcohol prepared to 11% volume mixed with fruit juice		Asn40: placebo, naltrexone The first alcohol challenge session preceded by pretreatment with placebo. The second alcohol challenge session preceded by pretreatment with naltrexone 50 mg as a single dose. placebo: placebo pills naltrexone : 50 mg of naltrexone prior to challenge session alcohol : 190 proof alcohol prepared to 11% volume mixed with fruit juice		Asp40: placebo, placebo prior Each alcohol challenge session preceded by pretreatment with placebo. placebo: placebo pills alcohol : 190 proof alcohol prepared to 11% volume mixed with fruit juice		Asp40: placebo, naltrexone The first alcohol challenge session preceded by pretreatment with placebo. The second alcohol challenge session preceded by pretreatment with naltrexone 50 mg as a single dose. placebo: placebo pills naltrexone : 50 mg of naltrexone prior to challenge session alcohol : 190 proof alcohol prepared to 11% volume mixed with fruit juice
All Cause Mortality
	Group 1: Asn40 Placebo Placebo		Group 2: Asn40 Placebo Naltrexone		Group 3: Asp40 Placebo Placebo		Group 4: Asp40 Placebo Naltrexone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/8 (0%)		0/4 (0%)		0/6 (0%)
Serious Adverse Events
	Group 1: Asn40 Placebo Placebo		Group 2: Asn40 Placebo Naltrexone		Group 3: Asp40 Placebo Placebo		Group 4: Asp40 Placebo Naltrexone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/8 (0%)		0/4 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Group 1: Asn40 Placebo Placebo		Group 2: Asn40 Placebo Naltrexone		Group 3: Asp40 Placebo Placebo		Group 4: Asp40 Placebo Naltrexone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/8 (0%)		0/4 (0%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.