Varenicline for Nicotine Dependence Among Those With HIV/AIDS

Phase 3

Completed

Conditions: Nicotine Dependence

Interventions: Drug: Placebo
Drug: Varenicline
Behavioral: Smoking Cessation Counseling

Registration Number: NCT01710137

Lead Sponsor: University of Pennsylvania

Brief Summary: Among people diagnosed with HIV/AIDS, the widespread use of highly active antiretroviral therapy (HAART) has greatly improved survival rates and changed the leading causes of death, from AIDS-related diseases to cardiovascular disease and lung cancer. Rates of tobacco use among individuals with HIV/AIDS are very high and varenicline may be particularly efficacious for treating nicotine dependence among individuals with HIV/AIDS. Through this trial, 310 smokers with HIV/AIDS will be randomized to varenicline plus 9 weeks of smoking cessation counseling or placebo plus 9 weeks of smoking cessation counseling. The investigators hypothesize that 1) varenicline and counseling will significantly increase end-of-treatment (week 12) and 24-week biochemically-confirmed abstinence, versus placebo and counseling; 2) quality of life will be rated higher in the varenicline and counseling group versus the placebo and counseling group, and there will be no significant differences between treatment arms in terms of the frequency of severe varenicline-related side effects; and 3) improved affect and reduced cognitive impairment will mediate the effect of varenicline therapy on quit rates.

Detailed Description: Among people diagnosed with HIV/AIDS, the widespread use of highly active antiretroviral therapy (HAART) has greatly improved survival rates and changed the leading causes of death, from AIDS-related diseases (e.g., non-Hodgkin's lymphoma, Kaposi sarcoma), to cardiovascular disease and lung cancer. As such, addressing modifiable risk factors for disease mortality among those with HIV/AIDS, including tobacco use, has become a critical priority. To date, only three smoking cessation clinical trials have been conducted with those with HIV/AIDS none of which investigated the efficacy of FDA-approved medications for nicotine dependence. Varenicline is an α4β2 nicotinic acetylcholine receptor partial agonist with greater efficacy for treating nicotine dependence than bupropion or nicotine patch. Varenicline may be particularly efficacious for treating nicotine dependence among individuals with HIV/AIDS given that depression symptoms and cognitive impairment are common in this population, increase during smoking abstinence and predict smoking relapse, and are significantly reduced by varenicline. Therefore, the investigators will conduct a randomized, double-blind, placebo-controlled trial of varenicline with smokers with HIV/AIDS. Specifically, 310 smokers with HIV/AIDS will be randomized to varenicline plus 9 weeks of smoking cessation counseling or placebo plus 9 weeks of smoking cessation counseling. The primary outcome variable for this study will be 7-day biochemically confirmed tobacco abstinence at weeks 12 and 24. Secondary outcomes include: prolonged abstinence to week 12, 18, and 24 (relapse defined as 7 consecutive days of self-reported smoking, after a 2-week grace period), continuous abstinence at weeks 12 and 24 (e.g., no smoking between quit day and follow-up), time to 7-day relapse (no grace period), and lapse and recovery events. The trial results may support the use of varenicline for the treatment of nicotine dependence among those with HIV/AIDS, thereby reducing tobacco-related morbidity and mortality in this population.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 179

Inclusion Criteria

Not provided

Exclusion Criteria

Smoking Behavior

Current enrollment or plans to enroll in another smoking cessation program in the next 7 months.
Regular (daily) use of chewing tobacco, snuff, snus, cigars, cigarillos, or pipes.
Current use or plans to use nicotine substitutes (gum, patch, lozenge, e-cigarette) or smoking cessation treatments in the next 7 months.
1. Note: Once participants are found eligible for the study, they are told they should refrain from using any nicotine replacement therapy (NRT) for the duration of the study. If a subject reports an isolated (non-daily) instance of NRT use during the study, they may be permitted to continue.

Alcohol/Drug Exclusion Criteria

Current untreated and unstable diagnosis of substance abuse or dependence (eligible if past use and if receiving treatment and stable for >30 days).
Positive urine drug screen (for cocaine and/or methamphetamines) at the Intake Session.
Breath Alcohol Concentration (BrAC) assessment greater than or equal to 0.01 at the Intake Session.

Medication Exclusion Criteria

Current use or recent discontinuation (within last 14 days) of the following medications:

Other smoking cessation medications (e.g. Zyban, Wellbutrin, Wellbutrin SR, Chantix)

a. Note: Once participants are found eligible for the study, they are instructed to only use the smoking cessation medication provided to them by the study staff. If a subject reports an isolated (non-daily) instance of using a non-study smoking cessation medication, the study physician and PI will evaluate the situation and determine if it is safe for the subject to continue participation.
Anti-psychotic medications.

Medical Exclusion Criteria

Women who are pregnant, planning a pregnancy within the next 7 months, or lactating.
Current diagnosis of unstable and untreated major depression, as determined by self-report & MINI (eligible if stable for >30 days).
Current or past diagnosis of psychotic disorder, as determined by self-report or MINI.
Any suicide risk score on MINI, current suicidal ideation on Columbia scale, or self-reported lifetime suicide attempt.
History of heart disease, stroke or MI, unstable angina, or tachycardia (if stable, requires Study Physician approval).
Uncontrolled hypertension (SBP >160 or DBP >100).

a. Note: If a participant presents with blood pressure greater than 160/100 at sessions occurring on Week 0 (Pre-Quit) or at any other point during the treatment period, they will not be provided with/able to continue on medication unless the study physician grants approval.
History of kidney or liver failure.
Abnormal ECG (unless approved by study physician).
Estimated creatinine clearance <50 mL/min, within 6 months prior to enrollment.
AST and/or ALT results greater than 2 times the upper limit of normal, within 6 months prior to enrollment.
Any impairment (physical, neurological, visual) preventing cognitive task performance.
Previous allergic reaction to varenicline.

General Exclusion Criteria

Any medical condition or concomitant medication that could compromise subject safety or treatment, as determined by the Principal Investigator and/or Study Physician.
Inability to provide informed consent or complete any of the study tasks as determined by the Principal Investigator and/or Study Physician.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	12 weeks of placebo + smoking cessation counseling Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally
Placebo	Smoking Cessation Counseling	12 weeks of placebo + smoking cessation counseling Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally
Varenicline	Varenicline	12 weeks of active varenicline + smoking cessation counseling Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally
Varenicline	Smoking Cessation Counseling	12 weeks of active varenicline + smoking cessation counseling Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally

Primary Outcome Measures

Name	Time	Method
Point Prevalence Tobacco Abstinence	Week 24	7-day biochemically-confirmed tobacco abstinence; biochemically-confirmed with urine cotinine.

Secondary Outcome Measures

Name	Time	Method
Quality of Life at Week 12	Week 12	The HIV/AIDS-Targeted Quality of Life scale measures overall functioning. Scale range from 7 - 35. Higher score indicates worse quality of life.
Time to 7-day Relapse	Week 24	days to smoking regularly for 7 days
Continuous Abstinence to Week 24	Weeks 24	No smoking between the quit day and the follow-up (Week 24).
Point Prevalence Tobacco Abstinence	Week 18	7-day biochemically-confirmed tobacco abstinence; biochemically-confirmed with urine cotinine.
Continuous Abstinence to Week 12	Weeks 12	No smoking between the quit day and the follow-up (week 12).