NALAPZ: An Exploratory Study of Naltrexone Plus Aripiprazole for Alcohol Dependence

• Sponsor: Medical University of South Carolina (Other)
• Overall Status: Completed
• CT.gov ID: NCT00667875
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
• Enrollment: 65
• Location: 1
• Arms: 3
• Duration (Months): 37
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

The principal aim of this exploratory study is to examine whether the addition of aripiprazole to naltrexone will enhance efficacy over naltrexone alone in a 16-week randomized, placebo-controlled clinical trial, in which all subjects will be provided medical management as delivered in the COMBINE Study (Anton et al, 2006). To test whether medication treatment will reduce drinking compared to placebo treatment alone in the context of medical management and whether naltrexone plus aripiprazole will reduce drinking compared to naltrexone treatment alone in the context of medical management.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Dependence	Drug: Placebo; Drug: Naltrexone; Drug: Naltrexone + Aripiprazole	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 65 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: An Exploratory Study of Naltrexone Plus Aripiprazole for Alcohol Dependence
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: May 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 1	Drug: Placebo; placebo
Active Comparator: 2 Naltrexone	Drug: Naltrexone; Naltrexone (25mg or 50 mg per titration schedule)
Active Comparator: 3 Naltrexone + Aripiprazole	Drug: Naltrexone + Aripiprazole; Naltrexone + Aripiprazole (5mg - 15mg per titration schedule)

Outcome Measures

Primary Outcome Measures

1. Drinks Per Drinking Day [16-week treatment period]

   Standard drinks per drinking day

2. Percent Heavy Drinking Days [16 weeks]

   percent of total 112 day trial in which heavy drinking occurred (>=4 for females, >=5 male)

Secondary Outcome Measures

1. Pill Counts During Treatment [16-week]

   Compliance with medication as determined by pill counts

2. Percent Riboflavin Positive Urine Samples as a Measure of Medication Compliance [16 weeks treatment trial]

   Riboflavin was added to each individual capsule of medication and measured as a proxy for compliance with the medication regime

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age 18 70

2. Subjects will meet criteria for primary alcohol dependence operationalized as follows:

1. Meets the DSM IV criteria for alcohol dependence including loss of control over drinking (criterion 3) B. Has not had more than one previous inpatient medical detoxification

1. Consumes, on average, at least 10 standard drinks per drinking day for men and 8 drinks per day for women in the 90 days pre-screening (to select an appropriately heavy drinking population)

2. Able to maintain sobriety for four days (with or without the aid of alcohol detoxification medications) as determined by self report, collateral report, and breathalyzer measurements

3. Able to read and understand questionnaires and informed consent

4. Lives within approximately 50 miles of the study site -

Exclusion Criteria:

1. Currently meets DSM IV criteria for any other psychoactive substance dependency disorder except nicotine dependence

2. Ever abused opiates

3. Any psychoactive substance abuse, except marijuana and nicotine, within the last 30 days as evidenced by subject report, collateral report, or urine drug screen

4. Meets DSM IV criteria for current axis I disorders of major depression, panic disorder, obsessive compulsive disorder, post traumatic stress syndrome, bipolar affective disorder, schizophrenia, or any other psychotic disorder or organic mental disorder

5. Meets DSM IV current criteria for dissociative disorder or eating disorders

6. Has current suicidal ideation or homicidal ideation

7. Need for maintenance or acute treatment with any psychoactive medication including anti-seizure medications

8. Current use of disulfiram

9. Clinically significant medical problems such as cardiovascular, renal, GI, or endocrine problem that would impair participation or limit medication ingestion

10. Hepatocellular disease indicated by elevations of SGPT (ALT) and SGOT (AST) of at least 3.0 times normal at screening and/or after 5 days abstinence

11. Sexually active female of child-bearing potential who is pregnant (by urine HCG), nursing, or who is not using a reliable form of birth control

12. Has current charges pending for a violent crime (not including DUI-related offenses)

13. Does not have a stable living situation and a reliable source of collateral reporting

14. Has taken an opiate antagonist drug in the last month

15. Has taken aripiprazole in the last month or has experienced adverse effects from it at any time in the past

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical University of South Carolina, Center for Drug and Alcohol Programs	Charleston	South Carolina	United States	29425

Sponsors and Collaborators

• Medical University of South Carolina
• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: Raymond F Anton, M.D., Medical University of South Carolina

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Raymond F. Anton, Distringuished University Professor, Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT00667875
• Other Study ID Numbers: ANTON-1R21AA017525-01; R21AA017525; NIH Grant AA017525-01
• First Posted: Apr 28, 2008
• Last Update Posted: Sep 29, 2017
• Last Verified: Aug 1, 2017

• Keywords provided by Raymond F. Anton, Distringuished University Professor, Medical University of South Carolina: Alcohol Dependence; Alcoholism; Naltrexone; Aripiprazole; Substance Abuse
• Additional relevant MeSH terms: Alcoholism; Naltrexone; Aripiprazole

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from the community in response to advertising in local papers, and radio
Pre-assignment Detail	Subjects were to remain abstinent for 4 days prior to starting treatment with the randomly assigned study drug.

Arm/Group Title	1 Placebo	2 Naltrexone	3 Naltrexone Plus Aripiprazole
Arm/Group Description	Placebo : placebo	Naltrexone Naltrexone : Naltrexone (25mg or 50 mg per titration schedule)	Naltrexone + Aripiprazole Naltrexone + Aripiprazole : Naltrexone + Aripiprazole (5mg - 15mg per titration schedule)
Period Title: Overall Study
STARTED	23	21	21
Subjects Included in Analysisd	20	21	19
COMPLETED	13	10	8
NOT COMPLETED	10	11	13

Baseline Characteristics

Arm/Group Title	1 Placebo	2 Naltrexone	3 Naltrexone Plus Aripiprazole	Total
Arm/Group Description	Placebo : placebo	Naltrexone Naltrexone : Naltrexone (25mg or 50 mg per titration schedule)	Naltrexone + Aripiprazole Naltrexone + Aripiprazole : Naltrexone + Aripiprazole (5mg - 15mg per titration schedule)	Total of all reporting groups
Overall Participants	23	21	21	65
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47 (9.6)	47.2 (11.3)	48.4 (10.2)	47.6 (10.2)
Sex: Female, Male (Count of Participants)
Female	7 30.4%	7 33.3%	9 42.9%	23 35.4%
Male	16 69.6%	14 66.7%	12 57.1%	42 64.6%

Outcome Measures

1. Primary Outcome

Title	Drinks Per Drinking Day
Description	Standard drinks per drinking day
Time Frame	16-week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Inactive Placebo	Naltrexone and Inactive Placebo Aripiprazole	Naltrexone + Aripiprazole
Arm/Group Description	Inactive placebo naltrexone + inactive placebo Aripiprazole	Naltrexone: Naltrexone (25mg or 50 mg per titration schedule)	Naltrexone + Aripiprazole: Naltrexone + Aripiprazole (5mg - 15mg per titration schedule)
Measure Participants	20	21	19
Mean (Standard Deviation) [drinks per drinking day]	7.2 (7.3)	7.8 (6.6)	5.2 (7.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inactive Placebo, Naltrexone and Inactive Placebo Aripiprazole, Naltrexone + Aripiprazole
	Comments	Analyzed as a mixed model, Group by time (4 time blocks) with an unstructured variance/covariance matrix. Baseline drinks per day was used as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.49
	Comments	The p value represents variation of the total 16 week trial over all three groups.
	Method	Mixed Models Analysis
	Comments

2. Primary Outcome

Title	Percent Heavy Drinking Days
Description	percent of total 112 day trial in which heavy drinking occurred (>=4 for females, >=5 male)
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo: Placebo	Naltrexone: Placebo Aripiprazole	Naltrexone:Aripiprazole
Arm/Group Description	Placebo naltrexone and placebo aripiprazole	Naltrexone Naltrexone: Naltrexone (25mg or 50 mg per titration schedule): placebo aripiprazole	Naltrexone + Aripiprazole Naltrexone + Aripiprazole: Naltrexone + Aripiprazole (5mg - 15mg per titration schedule)
Measure Participants	20	21	19
Mean (Standard Deviation) [percent of days]	10.54 (20.0)	16.7 (19.9)	7.34 (19.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inactive Placebo, Naltrexone and Inactive Placebo Aripiprazole, Naltrexone + Aripiprazole
	Comments	Analyzed as a mixed model (SPSS linear mixed) with an unstructured variance/covariance and baseline percent heavy drinking days as a covariate
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments	The p value represents variation of the total 16 week trial over all three groups.
	Method	Mixed Models Analysis
	Comments

3. Secondary Outcome

Title	Pill Counts During Treatment
Description	Compliance with medication as determined by pill counts
Time Frame	16-week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Placebo	2 Naltrexone	3 Naltrexone Plus Aripiprazole
Arm/Group Description	Placebo : placebo	Naltrexone Naltrexone : Naltrexone (25mg or 50 mg per titration schedule)	Naltrexone + Aripiprazole Naltrexone + Aripiprazole : Naltrexone + Aripiprazole (5mg - 15mg per titration schedule)
Measure Participants	20	21	19
Percent aripiprazole or aripiprazole placebo taken	96.4 (6.5)	97.0 (4.7)	84.2 (25.2)
Percent naltrexone or naltrexone placebo taken	96.8 (5.9)	96.9 (4.2)	86.4 (22.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inactive Placebo, Naltrexone and Inactive Placebo Aripiprazole, Naltrexone + Aripiprazole
	Comments
	Type of Statistical Test	Superiority
	Comments	Anova across all three treatment groups
Statistical Test of Hypothesis	p-Value	<.05
	Comments
	Method	ANOVA
	Comments	Naltrexone or naltrexone placebo pills taken F=3.9 df 2 Aripiprazole or aripiprazole placebo pills taken F=4.6 df 2

4. Secondary Outcome

Title	Percent Riboflavin Positive Urine Samples as a Measure of Medication Compliance
Description	Riboflavin was added to each individual capsule of medication and measured as a proxy for compliance with the medication regime
Time Frame	16 weeks treatment trial

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo: Placebo	Naltrexone: Placebo Aripiprazole	Naltrexone:Aripiprazole
Arm/Group Description	Placebo naltrexone and placebo aripiprazole	Naltrexone Naltrexone: Naltrexone (25mg or 50 mg per titration schedule): placebo aripiprazole	Naltrexone + Aripiprazole Naltrexone + Aripiprazole: Naltrexone + Aripiprazole (5mg - 15mg per titration schedule)
Measure Participants	20	21	19
Mean (Standard Deviation) [Percent of riboflavin positive samples]	74.9 (33.7)	85.1 (18.5)	62.1 (30.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inactive Placebo, Naltrexone and Inactive Placebo Aripiprazole, Naltrexone + Aripiprazole
	Comments	Anova across three groups
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.05
	Comments
	Method	ANOVA
	Comments	f 3.2 df 2

Adverse Events

Time Frame	Adverse event data were collected over 16 weeks following randomization visit.
Adverse Event Reporting Description	The SAFTEE was used to collect this data. Psychopharmacol Bull. 1986;22(2):343-81
Arm/Group Title	Inactive Placebo		Naltrexone and Inactive Placebo Aripiprazole		Naltrexone + Aripiprazole
Arm/Group Description	Inactive placebo naltrexone + inactive placebo Aripiprazole		Naltrexone: Naltrexone (25mg or 50 mg per titration schedule)		Naltrexone + Aripiprazole: Naltrexone + Aripiprazole (5mg - 15mg per titration schedule)
All Cause Mortality
	Inactive Placebo		Naltrexone and Inactive Placebo Aripiprazole		Naltrexone + Aripiprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/21 (0%)		0/21 (0%)
Serious Adverse Events
	Inactive Placebo		Naltrexone and Inactive Placebo Aripiprazole		Naltrexone + Aripiprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/21 (0%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	Inactive Placebo		Naltrexone and Inactive Placebo Aripiprazole		Naltrexone + Aripiprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/23 (91.3%)		20/21 (95.2%)		19/21 (90.5%)
Gastrointestinal disorders
Nausea and/or vomiting	6/23 (26.1%)	6	12/21 (57.1%)	20	10/21 (47.6%)	14
Diarrhea	4/23 (17.4%)	7	8/21 (38.1%)	15	3/21 (14.3%)	5
General disorders
Dizziness	6/23 (26.1%)	11	9/21 (42.9%)	17	10/21 (47.6%)	21
Headache	14/23 (60.9%)	34	10/21 (47.6%)	15	9/21 (42.9%)	20
Fatigue or tiredness	10/23 (43.5%)	37	16/21 (76.2%)	39	12/21 (57.1%)	20
Insomnia	9/23 (39.1%)	40	12/21 (57.1%)	33	9/21 (42.9%)	28
Somnolence	7/23 (30.4%)	9	9/21 (42.9%)	17	5/21 (23.8%)	8
Nervous system disorders
Nervousness/anxiety	12/23 (52.2%)	45	13/21 (61.9%)	34	11/21 (52.4%)	27

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.