Varenicline for Nicotine Dependence Among Those With HIV/AIDS

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of Pennsylvania
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Robert Schnoll, University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01710137
First received: October 8, 2012
Last updated: August 12, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Nicotine Dependence
Drug: Varenicline
Drug: Placebo
Behavioral: Smoking Cessation Counseling
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Placebo Controlled Trial of Varenicline for Smoking Among Those With HIV/AIDS

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Point prevalence tobacco abstinence [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    7-day biochemically-confirmed tobacco abstinence; biochemically-confirmed with urine cotinine.

  • Point prevalence tobacco abstinence [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    7-day biochemically-confirmed tobacco abstinence; biochemically-confirmed with urine cotinine.


Secondary Outcome Measures:
  • Quality of Life [ Time Frame: Weeks 12 & 24 ] [ Designated as safety issue: Yes ]
    The HIV/AIDS-Targeted Quality of Life scale measures overall functioning, which will be the primary measure of QOL for this study, but several subscales of QOL are also included such as life satisfaction, health worries, HIV mastery, financial worries, and disclosure worries. In addition, the investigators will compare treatment arms in terms of the frequency of severe side effects (individual and total).

  • Prolonged Abstinence [ Time Frame: Weeks 12 & 24 ] [ Designated as safety issue: No ]
    Relapse is 7 consecutive days of self-reported smoking, after a 2-week grace period.

  • Continuous Abstinence [ Time Frame: Weeks 12 & 24 ] [ Designated as safety issue: No ]
    No smoking between the quit day and the follow-up; no smoking during weeks 9-12 as measured in previous varenicline trials with the general population of smokers.

  • Time to 7-day relapse [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Smoking Rate [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Monitor changes in smoking rates (i.e., # cigarettes/day).

  • Lapse & Recovery Events [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Timing and rates of lapses (smoking episodes not lasting 7 days) and recovery events (return to 24-hour abstinence).

  • Point prevalence tobacco abstinence [ Time Frame: Week 18 ] [ Designated as safety issue: No ]
    7-day biochemically-confirmed tobacco abstinence; biochemically-confirmed with urine cotinine.


Estimated Enrollment: 350
Study Start Date: October 2012
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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

Drug: Varenicline
Other Name: Chantix
Behavioral: Smoking Cessation Counseling
Placebo Comparator: 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

Drug: Placebo Behavioral: Smoking Cessation Counseling

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01710137

Contacts
Contact: Amanda M Kaufmann 215-746-8434 akau@mail.med.upenn.edu

Locations
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Amanda M Kaufmann    215-746-8434    akau@mail.med.upenn.edu   
Principal Investigator: Robert A Schnoll, PhD         
Sponsors and Collaborators
University of Pennsylvania
Investigators
Principal Investigator: Robert A Schnoll, PhD University of Pennsylvania
  More Information

No publications provided

Responsible Party: Robert Schnoll, Associate Professor, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01710137     History of Changes
Other Study ID Numbers: R01 DA033681-01, 815435, R01DA033681
Study First Received: October 8, 2012
Last Updated: August 12, 2014
Health Authority: United States: Data and Safety Monitoring Board
United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Pennsylvania:
Smoking cessation
Nicotine dependence
Varenicline
Chantix
HIV
AIDS

Additional relevant MeSH terms:
Tobacco Use Disorder
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Varenicline
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2014