Human Laboratory Study of Varenicline for Alcohol Use Disorder

This study is a double-blind, randomized, placebo-controlled, parallel group, two-site study designed to assess the effects of varenicline as compared with placebo on responses to in vivo alcohol cue exposure in the human laboratory setting.

Study Overview

• Status: Completed
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: Varenicline; Drug: Placebo oral capsule

Detailed Description

This study is a double-blind, randomized, placebo-controlled, parallel group, two-site study designed to assess the effects of varenicline as compared with placebo on responses to in vivo alcohol cue exposure in the human laboratory setting. After signing informed consent, subjects will be screened for eligibility including medical history, physical examination, vital signs, electrocardiogram (ECG), drinking history by the timeline follow-back (TLFB) method, alcohol breathalyzer test, Clinical Institute Withdrawal Assessment for Alcohol-revised (CIWA), medication use, MINI neuropsychiatric interview, urine toxicology screen, clinical chemistry, response to cue reactivity, and Columbia Suicide Severity Rating Scale (CSSR-S). Women of child-bearting potential will have a pregnancy test. If eligible for the study, subjects will be randomized using a stratified permuted block randomization procedure in an approximate 1:1 ratio (targeting 24 subjects per group - 12 subjects per group per site) to receive either varenicline or placebo for 6 weeks. Any nicotine use versus no use (cigarettes, cigars, chewing tobacco, electronic cigarettes, etc.) in the week before randomization is the stratification variable.

Varenicline or matched placebo will be titrated over the first week of the study up the maintenance dose of 1 mg (active) or two capsules (placebo) taken orally BID for an additional 5 weeks. Subjects will be seen in the clinic at screening, at randomization and 6 other times during the study. A final follow-up telephone interview will occur during Week 9 (2 weeks after the end of study visit).

After the first two weeks and after five weeks of investigational product administration at Study Week 3 and Study Week 6, respectively, subjects will undergo a cue reactivity paradigm session (HLAB) including 4 individual visual analog scale (VAS) items assessing alcohol craving, 2 VAS items assessing emotional reactivity to picture stimuli, and 2 items assessing emotional manipulation. Immediately after the HLAB session, subjects will view each picture again and record the emotion felt using the Self-Manikin Assessment (SAM).

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University School of Medicine
  • Rhode Island
    • Providence, Rhode Island, United States, 02912
      • Brown University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

To be eligible, the subject must:

• Be at least 21 years of age.
• Meet the DSM 5 criteria for alcohol use disorder of a least moderate severity (AUD-MS).
• Be seeking treatment for AUD and desire a reduction or cessation of drinking.
• Be able to verbalize an understanding of the consent form, able to provide written informed consent, verbalize willingness to complete study procedures, able to understand written and oral instructions in English and able to complete the questionnaires required by the protocol.

• Agree (if the subject is female and of child bearing potential) to use at least one of the following methods of birth control, unless she is surgically sterile, partner is surgically sterile or she is postmenopausal:

  1. oral contraceptives,
  2. contraceptive sponge,
  3. patch,
  4. double barrier (diaphragm/spermicidal or condom/spermicidal),
  5. intrauterine contraceptive system,
  6. levonorgestrel implant,
  7. medroxyprogesterone acetate contraceptive injection,
  8. complete abstinence from sexual intercourse, and/or
  9. hormonal vaginal contraceptive ring.
• Be able to take oral medication and be willing to adhere to the medication regimen.
• Complete all assessments required at screening and baseline.
• Have a place to live in the 2 weeks prior to randomization and not be at risk that s/he will lose his/her housing in the next 2 months.
• Not anticipate any significant problems with transportation arrangements or available time to travel to the study site over the next 2 months.
• Not have any unresolved legal problems that could jeopardize continuation or completion of the study.
• And others.

Exclusion Criteria:

• Contact site for additional information

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: varenicline; 1 mg BID (2 capsules BID)	Drug: Varenicline; 1 mg BID; Other Names: Chantix
Placebo Comparator: Placebo; 1 mg BID (2 capsules BID)	Drug: Placebo oral capsule; 1 mg BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cue-elicited Craving	The primary outcome is cue-elicited alcohol craving, operationalized as the difference in Visual Analog Scale (VAS) craving for alcohol when exposed to an alcohol cue minus the VAS craving for alcohol when exposed to a water cue. The VAS has a minimum value of 0 and maximum value of 20; higher scores indicate more craving (a worse outcome).	Study Week 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Heavy Drinking Days	The percentage of heavy drinking days during the last month of treatment (weeks 3-6). A heavy drinking day is defined as 4 or more drinks on a single day for females and 5 or more drinks on a single day for males.	Weeks 3-6
The Percentage of Subjects Abstinent During the Last Month of Treatment (Weeks 3-6).	The percentage of subjects abstinent from alcohol during the last month of treatment (weeks 3-6).	Weeks 3-6
Cigarettes Smoked Per Week	The number of cigarettes smoked per week during the last month of treatment (weeks 3-6) computed only among participants who were smokers at baseline (varenicline n=11; placebo n=11). Note: cigarettes smoked per week outcome data was missing for two of the varenicline participants resulting in n=9 available for analysis.	Weeks 3-6
Penn Alcohol Craving Scale	Penn Alcohol Craving Scale (higher numbers are indicative of more craving for alcohol); min = 0, max = 30. The measure was assessed at Study Weeks 3, 4, 5, and 6. The reported outcome is the adjusted mean total score across weeks 3-6.	Study Weeks 3, 4, 5, 6 (assessed weekly during this period)

Collaborators and Investigators

• Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Study Director: Raye Litten, PhD, National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2017
• Primary Completion (Actual): July 1, 2018
• Study Completion (Actual): July 7, 2018

Study Registration Dates

• First Submitted: January 26, 2017
• First Submitted That Met QC Criteria: January 26, 2017
• First Posted (Estimate): January 30, 2017

Study Record Updates

• Last Update Posted (Actual): October 23, 2019
• Last Update Submitted That Met QC Criteria: October 22, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol Drinking; Alcoholism; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Nicotinic Agonists; Cholinergic Agonists; Varenicline
• Other Study ID Numbers: HLAB 001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No