The Canadian HIV Quit Smoking Trial: Tackling the Co-morbidities of Depression and Cardiovascular Disease in HIV+ Smokers

Study Overview
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Brief Summary
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The objectives of this trial are: Primary objectives: To determine among HIV+ individuals whether varenicline or NRT is more effective at helping individuals remain abstinent from smoking tobacco. To determine among HIV+ individuals whether varenicline or NRT has the lowest side-effect profile. To determine if the HIV tailored Quit Smoking Counselling Intervention, plus smoking cessation drug therapy, improves smoking cessation rates compared to smoking cessation drug therapy alone with usual care. Secondary objective: 1. To determine whether the use of varenicline/NRT is safe in HIV+ patients who exhibit depressive symptoms. Hypothesis: That varenicline will result in higher quit smoking rates and that NRT will result in a lower side effect profile. Further, the HIV tailored quit smoking intervention will result in higher rates of smoking cessation over and above the pharmacological treatment alone. And finally, varenicline will be safe to use for HIV + individuals who exhibit depressive symptoms.

Official Title
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The Canadian HIV Quit Smoking Trial: Tackling the Co-morbidities of Depression and Cardiovascular Disease in HIV+ Smokers

Conditions
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HIV, Smoking Cessation

Intervention / Treatment
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* Drug: Nicotine Replacement Therapy (NRT)
* Drug: Varenicline
* Behavioral: HIV Tailored Quit Smoking Counseling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV positive Adult (aged 18 or older) Current smoker (more than 5 cigarettes per day) Willing to set a date to quit smoking within the next 2-4 weeks Currently on ART with an undetectable HIV viral load Able to read/speak English or French Able to provide written, informed consent as approved by the Ottawa Health Science Network Research Ethics Board and REBs at participating HIV clinic sites Exclusion Criteria: Contraindications to nicotine replacement therapy such as allergy to adhesive, serious cardiac arrhythmias (e.g., tachycardia), or vasospastic disease (e.g., Buerger's disease, Prinzmetal's variant angina) Contraindications to varenicline such as hypersensitivity to varenicline or to any ingredient in the formulation or component of the container. Reported previous severe intolerances to nausea or gastrointestinal symptoms. Pregnant, lactating or planning to become pregnant during the study period or refuses a serum beta-HCG test. Current severe renal impairment or currently taking Cimetidine Previous or current seizure disorder and/or is taking anti-epileptic drugs Psychosis and/or is taking anti-psychotic drugs Diagnosed with severe major depressive episode requiring hospitalization within the past 12 months, previous psychiatric inpatient admission for any cause within the past 12 months, suicide attempt within the past 12 months active or current suicidal ideations as assessed by the BDI-II. Current use of bupropion, varenicline or any nicotine replacement therapy. Use of substances (e.g., crack cocaine) that would interfere with a participant's ability to adhere to the study schedule; determined by site coordinator's discretion.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NRT arm<br>Drug: Nicotine Replacement Therapy (Nico-Derm® and Nicorette®) Dose: 7mg - 42mg depending on # of cigarettes smoked per day at study baseline, and withdrawal symptoms. Mode of Administration: Transdermal Patch Duration of Treatment: up to 24 Weeks Additionally, participants will be provided with a supply of short-acting nicotine gum in order to supplement their long acting NRT patch regimen. Individuals who smoke their first cigarette more than 30 minutes after waking are advised to use the 2 mg NRT gum. Participants who smoke their first cigarette within 30 minutes of waking will be advised to use the 4 mg NRT gum. Both NRT gum dosages will be recommended for use on an ad lib basis to address cravings and/or withdrawal symptoms, up to a maximum of 12 pieces of NRT gum per day. | Drug: Nicotine Replacement Therapy (NRT)<br> <br> * Other names: the gum;|
| Active Comparator: NRT and HIV Tailored Quit Smoking Counseling<br>Drug: Nicotine Replacement Therapy (Nico-Derm®) Dose: 7mg - 42mg depending on # of cigarettes smoked per day at study randomization and withdrawal symptoms. Mode of Administration: Transdermal Patch Duration of Treatment: up to 24 Weeks HIV tailored Smoking Cessation Counseling: The counseling consists of face-to-face sessions with a trained smoking cessation counselor at the start of the study, on your chosen quit date, and then at weeks 4, 8, 12 and 24; supportive telephone calls if needed. | Drug: Nicotine Replacement Therapy (NRT)<br> <br> * Other names: the gum;Behavioral: HIV Tailored Quit Smoking Counseling<br>* A cognitive behavioral therapy (CBT) oriented smoking cessation program tailored to HIV positive individuals. People Living with HIV/AIDS (PHA) tailored Canadian HIV Quit Smoking Counseling Intervention. It consists of face-to-face counseling sessions with a trained smoking cessation counsellor at randomization, on the identified quit date, and then at weeks 4, 8, 12, and 24.<br>* Other names: Ottawa Model for Smoking Cessation;|
| Active Comparator: Varenicline (VR) Arm<br>Drug: Varenicline (Champix®) Doses: 0.5 mg once daily for 3 days(i.e.day 1-3 of the week prior to quit date) 0.5 mg twice daily for 4 days i.e. day 4-7) and 1 mg twice daily for the remainder of the treatment period Mode of Administration: Oral Duration of Treatment: 24 Weeks (+ 1 Week of Dose Escalation, total of 25 weeks) | Drug: Varenicline<br> <br> * Other names: Champix;|
| Active Comparator: Varenicline (VR) and HIV Tailored Quit Smoking Counseling<br>Drug: Varenicline (Champix®) 0.5 mg once daily for 3 days(i.e.day 1-3 of the week prior to quit date) 0.5 mg twice daily for 4 days i.e. day 4-7) and 1 mg twice daily for the remainder of the treatment period Mode of Administration: Oral Duration of Treatment: 24 Weeks (+ 1 Week of Dose Escalation, total of 25 weeks) Intervention: HIV tailored Smoking Cessation Counseling: The counseling consists of face-to-face sessions with a trained smoking cessation counselor at the start of the study, on your chosen quit date, and then at weeks 4, 8, 12 and 24; supportive telephone calls if needed. | Drug: Varenicline<br> <br> * Other names: Champix;Behavioral: HIV Tailored Quit Smoking Counseling<br>* A cognitive behavioral therapy (CBT) oriented smoking cessation program tailored to HIV positive individuals. People Living with HIV/AIDS (PHA) tailored Canadian HIV Quit Smoking Counseling Intervention. It consists of face-to-face counseling sessions with a trained smoking cessation counsellor at randomization, on the identified quit date, and then at weeks 4, 8, 12, and 24.<br>* Other names: Ottawa Model for Smoking Cessation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Smoking Status | The primary study end-point will be seven-day self-reported abstinence, and four week continuous abstinence rates at week 48, confirmed by expired carbon monoxide levels measured using a piCO+ Smokerlyzer (Smoke free defined as exhaled CO < 10 ppm). Study participants who are lost to follow-up (e.g., study drop-outs and those unavailable for follow-up) will be considered as smokers for the purposes of outcome analyses. | at week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Smoking Status: self report | Seven-day point-prevalence, and 4-week continuous abstinence(if time interval permits), assessed by self-report and by expired carbon monoxide levels measured using a piCO+ Smokerlyzer. In addition, self-reported 4-week continuous abstinence rates (CAR) will be reported. | quit date, weeks 4,8,12,16,20,24 and 48 | 
| Smoking status: CO expired | Smoke free status will be objectively measured by exhaled CO levels (<10ppm) with a Bedfont Smokerlyzer instrument. | randomization, quit date, 4, 8, 12, 16, 20, 24 | 
| Smoking cessation treatment integrity and patient satisfaction | Study Medication: Adherence to NRT and varenicline will be assessed by participant self-reported adherence to medication at each study visit. Counseling Intervention: Each clinic site will have an HIV clinic health care provider who will be trained in administering the standardized HIV quit smoking intervention. Program Satisfaction Form will be completed by all study participants at the end of the study. At post-quit dates, treatment adherence will be assessed by a self-report measure of the amount of NRT or varenicline taken, number of cigarettes smoked in the previous 7 days, and marked changes in mood. Study coordinator will assess rates of discontinuation of varenicline or NRT. Participants who discontinue varenicline or NRT will still be followed according to the original schedule. | Baseline through Week 48 | 
| Behavioral-Psychosocial | The Minnesota Nicotine Withdrawal Scale The Center for Epidemiological Studies Depression Scale Smoking Self-Efficacy Questionnaire EuroQol(EQ-5D)This scale is a brief, standardized, generic measure of HR-QOL that provides a 5-item profile of patient function and a global health state rating Beck Depression Inventory Experiences in Close Relationships Stages of Change Questionnaire Adherence to Treatment Questionnaire Life Events Questionnaire Use of Cessation Resources Survey | Baseline to Week 48 | 
| Cardiovascular Parameters | The following parameters will be compared: Weight Height Waist circumference (defined by Heart and Stroke Foundation) Blood pressure | From baseline through 48 weeks | 
| Immune Function | Changes in: CD4-T-lymphocyte count and percentage HIV viral load CD8-T-lymphocyte count and percentage | 12, 24, and 48 weeks |