Varenicline for Nicotine Dependence Among Those With HIV/AIDS

Nicotine Dependence Clinical Trial

Official title:

A Placebo Controlled Trial of Varenicline for Smoking Among Those With HIV/AIDS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01710137
• Other study ID #: R01DA033681-01
• Secondary ID: 815435R01DA03368
• Status: Completed
• Phase: Phase 3
• Start date: October 2012
• Est. completion date: September 2018

Study information

• Verified date: September 2019
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 179
• Est. completion date: September 2018
• Est. primary completion date: September 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

1. 18 years of age or older who self-report smoking at least 5 cigarettes (menthol and non-menthol) per day, on average.

2. Diagnosed with HIV infection and exhibiting viral load of < 1000 copies/mL and CD4+ counts of > 200 cells/mm3 within 6 months prior to enrollment.

3. Able to use varenicline safely, based on a medical evaluation including medical history and physical examination, and psychiatric evaluation.

4. Residing in the geographic area for at least 7 months.

5. Women of childbearing potential (based on medical history and physical exam) must consent to use a medically accepted method of birth control (e.g., condoms and spermicide, oral contraceptive, Depo-Provera injection, contraceptive patch, tubal ligation) or abstain from sexual intercourse during the time they are taking study medication and for at least one month after the medication period ends.

6. If current or past diagnosis of bipolar disorder (I, II, or NOS), eligible if:

1. No psychotic features

2. MADRS: total score < 8 (past 4 weeks), suicidal item score < 1 (past 4 weeks)

3. Y-MRS: total score < 8 (past 4 weeks), irritability, speech content, disruptive, or aggressive behavior items score < 3 (past 4 weeks)

4. No psychiatric hospitalization or Emergency Room visits for psychiatric issues in the past 6 months

5. No aggressive or violent acts or behavior in the past 6 months

7. Able to communicate fluently in English.

8. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the combined consent/HIPAA form.

Exclusion Criteria:

Smoking Behavior

1. Current enrollment or plans to enroll in another smoking cessation program in the next 7 months.

2. Regular (daily) use of chewing tobacco, snuff, snus, cigars, cigarillos, or pipes.

3. 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

1. Current untreated and unstable diagnosis of substance abuse or dependence (eligible if past use and if receiving treatment and stable for >30 days).

2. Positive urine drug screen (for cocaine and/or methamphetamines) at the Intake Session.

3. 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:

1. 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.

2. Anti-psychotic medications.

Medical Exclusion Criteria

1. Women who are pregnant, planning a pregnancy within the next 7 months, or lactating.

2. Current diagnosis of unstable and untreated major depression, as determined by self-report & MINI (eligible if stable for >30 days).

3. Current or past diagnosis of psychotic disorder, as determined by self-report or MINI.

4. Any suicide risk score on MINI, current suicidal ideation on Columbia scale, or self-reported lifetime suicide attempt.

5. History of heart disease, stroke or MI, unstable angina, or tachycardia (if stable, requires Study Physician approval).

6. 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.

7. History of kidney or liver failure.

8. Abnormal ECG (unless approved by study physician).

9. Estimated creatinine clearance <50 mL/min, within 6 months prior to enrollment.

10. AST and/or ALT results greater than 2 times the upper limit of normal, within 6 months prior to enrollment.

11. Any impairment (physical, neurological, visual) preventing cognitive task performance.

12. Previous allergic reaction to varenicline.

General Exclusion Criteria

1. Any medical condition or concomitant medication that could compromise subject safety or treatment, as determined by the Principal Investigator and/or Study Physician.

2. Inability to provide informed consent or complete any of the study tasks as determined by the Principal Investigator and/or Study Physician.

Related Conditions & MeSH terms

• Nicotine Dependence
• Tobacco Use Disorder

Intervention

Drug:
• Varenicline

• Placebo

Behavioral:
• Smoking Cessation Counseling

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pennsylvania	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Point Prevalence Tobacco Abstinence	7-day biochemically-confirmed tobacco abstinence; biochemically-confirmed with urine cotinine.	Week 12
Primary	Point Prevalence Tobacco Abstinence	7-day biochemically-confirmed tobacco abstinence; biochemically-confirmed with urine cotinine.	Week 24
Secondary	Quality of Life at 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.	Week 12
Secondary	Continuous Abstinence to Week 12	No smoking between the quit day and the follow-up (week 12).	Weeks 12
Secondary	Continuous Abstinence to Week 24	No smoking between the quit day and the follow-up (Week 24).	Weeks 24
Secondary	Time to 7-day Relapse	days to smoking regularly for 7 days	Week 24
Secondary	Point Prevalence Tobacco Abstinence	7-day biochemically-confirmed tobacco abstinence; biochemically-confirmed with urine cotinine.	Week 18