ChA: Varenicline (Chantix™) for the Treatment of Alcohol Dependence

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT00705523
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 40
• Location: 1
• Arms: 2
• Duration (Months): 42
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the efficacy of varenicline (Chantix™) for the treatment of alcohol dependence.

Condition or Disease	Intervention/Treatment	Phase
Alcoholism	Drug: varenicline; Drug: placebo	Phase 2

Detailed Description

By both providing a low level of reinforcement and down-grading any "high" associated with concurrent administration of the abused drug, combined agonist/antagonist therapies promote both initial and sustained abstinence. Based on varenicline's specific affinity for the nicotinic acetylcholine receptors that are implicated in alcohol reward circuitry, it appears to be a good candidate for treatment of alcohol dependence. Alcohol can exert its reinforcing and dopamine-enhancing effects through activation of nicotinic receptors. In addition to its partial agonist activity at heteromeric α4β2 nicotinic acetylcholine receptors, varenicline has also been shown to be a full agonist at homomeric α7 nicotinic acetylcholine receptors. That full agonism at α7 may be key in reducing alcohol withdrawal and craving during early alcohol abstinence, and thus reducing relapse, as α7 receptors are implicated in the neural reward circuitry activated by alcohol use.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase II, Randomized, Double-Blind Pilot Trial of Varenicline (Chantix™) for the Treatment of Alcohol Dependence
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Mar 1, 2010
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1	Drug: varenicline; 1.0 mg BID for 12 weeks; Other Names: Chantix
Placebo Comparator: 2	Drug: placebo; BID 12 weeks

Outcome Measures

Primary Outcome Measures

1. Rate of Heavy Drinking Days Per Week. [12 weeks of treatment and one month follow-up]

   Rate of heavy drinking days per week (defined as five drinks per day for men, four drinks per day for women) as determined by self-report on the time-line follow-back (TLFB).

Secondary Outcome Measures

1. Addiction Severity Index (ASI) Alcohol Composite Score at End of Study. [12 weeks of treatment, with a follow-up one month after treatment]

   The Addiction Severity Index (ASI) is a semistructured interview that measures the severity of addiction in 25 questions concerning seven problem areas: medical problems, employment problems, drug use, alcohol use, family and social problems, criminality, and psychiatric problems. Each problem area is measured as its own Compsite Score. Each Composite Score total ranges between 0 (no endorsement of any problems) and 1 (maximal endorsement of all problems). Higher scores (i.e., those closer to 1) on each Composite Score indicate more difficulty/lower functioning in that area, while lower scores (i.e., those closer to 0) indicate higher functioning/less difficulty in that area. As such, the Addiction Severity Index (ASI) Alcohol Composite Total Score must fall between 0 and 1, and scores closer to 1 suggest continued problem drinking.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• 1. Males and females, 18-70 years old.
• 1. Meets DSM-IV criteria for current diagnoses of alcohol dependence, determined by the SCID-IV (First, 1996).
• 1. Meets the following drinking criteria as measured by the Timeline Followback (TLFB) (Sobell, 1995)

• drank within 30 days of intake day,

• reports a minimum of 48 standard alcoholic drinks (avg. 12 drinks/wk) in a consecutive 30-day period over the 90-day period prior to starting intake (i.e., a minimum of 40% days drinking), and

• has 2 or more days of heavy drinking (defined as 5 or more drinks per day in males and 4 or more drinks per day in females) in this same pre-treatment period.

• 1. Three consecutive days of abstinence from alcohol, determined by self-reports and confirmed by a negative breathalyzer tests immediately before the day of randomization, and a Clinical Institute Withdrawal Scale for Alcohol (CIWA-AR) (Sullivan, 1989) score below eight on the day of randomization.
• 1. Lives a commutable distance from the TRC and agrees to attend all research visits including follow-up visits.

• Speaks, understands, and prints in English.

Exclusion Criteria:

• Has evidence of dependence on a substance other than alcohol (except nicotine or marijuana); or tests positive on the urine drug screen and on a single allowed retest, during the screening week, with the exception of a THC positive urine, and/or a).positive result for benzodiazepines prescribed by a doctor for medically indicated detox (prescription required).

• Has hepatocellular disease indicated by elevations of SGPT (ALT) and SGOT (AST) of at least 4.5 times normal after the required 3 days of abstinence, or elevated bilirubin (>1.3) (one retest allowed at the discretion of the Medical Director).

• Meets diagnostic criteria for a current unstable or serious psychiatric or medical illness. For example, bipolar affective disorder, schizophrenia or any other psychotic disorder, or organic mental disorder; has serious heart, lung, kidney, immune system, GI tract (ulcerative colitis, regional enteritis, or gastrointestinal bleeding) disease.

• Has taken any psychotropic medications (including disulfiram, naltrexone or acamprosate) regularly within the last 2 weeks or needs immediate treatment with a psychotropic medication (with the exception of detoxification medications or benadryl used sparingly for sleep).

• Tests positive on a pregnancy test, is contemplating pregnancy in the next 12 months, is nursing, or is not using an effective contraceptive method if the subject is of child-bearing potential.

• Has participated in any investigational drug trial within 30 days prior to the study. Subjects mandated to treatment based upon a legal decision or as a condition of employment. This will be assessed by the subject's self-report.

• Known hypersensitivity to varenicline.

• Subjects with known AIDS or other serious illnesses that may require hospitalization during the study.

• Clinical laboratory tests (CBC, blood chemistries, urinalysis) outside normal limits that are clinically unacceptable to the Principal Investigator. (ECG 1st degree heart block, sinus tachycardia, left axis deviation, and nonspecific ST or T wave changes are allowed; liver function tests [LFTs] <5 x ULN are acceptable).

Contacts and Locations

Locations

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

Sponsors and Collaborators

• University of Pennsylvania
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Jennifer G Plebani, PhD, University of Pennsylvania, Treatment Research Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jennifer Plebani, Principal Investigator, National Institute on Drug Abuse (NIDA)
• ClinicalTrials.gov Identifier: NCT00705523
• Other Study ID Numbers: ChA - 807226; P60DA005186
• First Posted: Jun 26, 2008
• Last Update Posted: Jun 2, 2015
• Last Verified: Jun 1, 2015

• Keywords provided by Jennifer Plebani, Principal Investigator, National Institute on Drug Abuse (NIDA): alcohol; treatment; nicotinic acetylcholine receptors; pharmacotherapy; outpatient
• Additional relevant MeSH terms: Alcoholism; Varenicline

Study Results

Participant Flow

Arm/Group Title	Varenicline	Placebo
Arm/Group Description	varenicline : 1.0 mg BID for 12 weeks	placebo : BID 12 weeks
Period Title: Overall Study
STARTED	19	21
COMPLETED	17	18
NOT COMPLETED	2	3

Baseline Characteristics

Arm/Group Title	Varenicline	Placebo	Total
Arm/Group Description	Titrated 0.5mg o.d. for days 1-3, 0.5mg b.i.d. for days 4-7, up to full dose of 1 mg/day by the end of the first week. Then 1 mg/day for remaining weeks.	placebo : BID 12 weeks	Total of all reporting groups
Overall Participants	19	21	40
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	19 100%	21 100%	40 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.8 (12.3)	48.1 (10.5)	46.5 (11.7)
Sex: Female, Male (Count of Participants)
Female	4 21.1%	2 9.5%	6 15%
Male	15 78.9%	19 90.5%	34 85%
Region of Enrollment (participants) [Number]
United States	19 100%	21 100%	40 100%
ASI Alcohol Composite Score, Baseline (Alcohol Composite Score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Alcohol Composite Score]	0.61 (0.16)	0.60 (0.15)	0.61 (0.16)
Days of Alcohol Use in Past 30 Days (Drinking Days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Drinking Days]	18.4 (8.8)	17.6 (9.1)	18.0 (8.95)

Outcome Measures

1. Primary Outcome

Title	Rate of Heavy Drinking Days Per Week.
Description	Rate of heavy drinking days per week (defined as five drinks per day for men, four drinks per day for women) as determined by self-report on the time-line follow-back (TLFB).
Time Frame	12 weeks of treatment and one month follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Varenicline	Placebo
Arm/Group Description	Titrated 0.5mg o.d. for days 1-3, 0.5mg b.i.d. for days 4-7, up to full dose of 1 mg/day by the end of the first week. Then 1 mg/day for remaining weeks.	placebo : BID 12 weeks
Measure Participants	19	21
Median (Standard Deviation) [rate of heavy drinking days per week]	.89 (.18)	1.21 (.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Varenicline, Placebo
	Comments	Self-reported drinking results, as gathered by the TLFB, were compared by the generalized estimating equations (GEE) (Diggle et al., 1994), using Poisson models for counts of drinking and heavy drinking days, and logistic regression models for absence/presence binary indicators of drinking. In the GEE model, the pre-treatment of the response was included as a covariate, together with the treatment group indicator, and a linear time effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.10
	Comments
	Method	Regression, Logistic
	Comments	beta=-0.67, exp(beta)=0.51, chi-squared(1) = 0.2.71

2. Secondary Outcome

Title	Addiction Severity Index (ASI) Alcohol Composite Score at End of Study.
Description	The Addiction Severity Index (ASI) is a semistructured interview that measures the severity of addiction in 25 questions concerning seven problem areas: medical problems, employment problems, drug use, alcohol use, family and social problems, criminality, and psychiatric problems. Each problem area is measured as its own Compsite Score. Each Composite Score total ranges between 0 (no endorsement of any problems) and 1 (maximal endorsement of all problems). Higher scores (i.e., those closer to 1) on each Composite Score indicate more difficulty/lower functioning in that area, while lower scores (i.e., those closer to 0) indicate higher functioning/less difficulty in that area. As such, the Addiction Severity Index (ASI) Alcohol Composite Total Score must fall between 0 and 1, and scores closer to 1 suggest continued problem drinking.
Time Frame	12 weeks of treatment, with a follow-up one month after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Varenicline	Placebo
Arm/Group Description	Titrated 0.5mg o.d. for days 1-3, 0.5mg b.i.d. for days 4-7, up to full dose of 1 mg/day by the end of the first week. Then 1 mg/day for remaining weeks.	placebo : BID 12 weeks
Measure Participants	19	21
Mean (Standard Deviation) [alcohol composite score]	0.12 (0.20)	0.29 (0.23)

Adverse Events

Arm/Group Title	Varenicline		Placebo
Arm/Group Description	varenicline : 1.0 mg BID for 12 weeks		placebo : BID 12 weeks
All Cause Mortality
	Varenicline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Varenicline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	Varenicline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/19 (89.5%)		19/21 (90.5%)
Gastrointestinal disorders
Diarrhea	4/19 (21.1%)	7	2/21 (9.5%)	3
Nausea	3/19 (15.8%)	4	3/21 (14.3%)	3
General disorders
Headache	5/19 (26.3%)	5	3/21 (14.3%)	3
Body aches/paines	5/19 (26.3%)	5	4/21 (19%)	4
Blood pressure elevation	1/19 (5.3%)	1	2/21 (9.5%)	2
Cough	1/19 (5.3%)	1	1/21 (4.8%)	1
Nighmare	2/19 (10.5%)	3	0/21 (0%)	0
Insomnia	2/19 (10.5%)	2	2/21 (9.5%)	2
Vivid dreams	4/19 (21.1%)	4	3/21 (14.3%)	3
Psychiatric disorders
PTSD-like episode	1/19 (5.3%)	1	0/21 (0%)	0
Depressed mood	2/19 (10.5%)	4	2/21 (9.5%)	2
Anxiety	1/19 (5.3%)	1	2/21 (9.5%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.