A Smart Approach to Treating Tobacco Use Disorder in Persons Living With HIV

Study Overview
=================
Brief Summary
-----------------
Many people living with HIV (PLWH) smoke. Smoking in these individuals is often undertreated. This study plans to assess the ability of various clinical pathways involving tobacco treatment medications and contingency management (paying smokers for not smoking) to improve smoking cessation in a group of PLWH.

Detailed Description
-----------------
Using a Sequential Multiple Assignment Randomized Trial (SMART) design, this project is a two-arm, two-stage randomized trial of 632 adult PWH who smoke cigarettes and receive care in one of three health systems. At inception, participants will be randomized to either combination nicotine replacement therapy (NRT, patch + short-acting NRT) or combination NRT+contingency management (CM). At 12 weeks, responders (non-smoking participants confirmed by exhaled carbon monoxide [eCO]) in both arms will receive 12 more weeks of the same treatment. Non-responders (participants with continued smoking by self-report and/or eCO) in both the NRT and NRT+CM arms will be re-randomized to 12 weeks of treatment, either with medication switch to oral medication, varenicline or bupropion, or intensified level of CM (start CM if no CM during first 12 weeks, or CM with higher reward schedule [CM plus] if NRT+CM group initially). The intervention will be delivered by trained clinical pharmacists. The primary outcome will be eCO-confirmed abstinence at 24 weeks post-enrollment. The specific aims of the proposed study are to: (1) identify the optimal adaptive approach to promote eCO-confirmed smoking abstinence (2) study the effectiveness of various adaptive strategies on CD4 count, HIV viral suppression, and VACS index (validated measure of morbidity and mortality risk); and (3) grounded in implementation science and using aHybrid Effectiveness-Implementation Type I design, identify barriers and facilitators to delivering our intervention to inform future implementation.

Official Title
-----------------
A Smart Approach to Treating Tobacco Use Disorder in Persons Living With HIV

Conditions
-----------------
Tobacco Use Cessation

Intervention / Treatment
-----------------
* Drug: Nicotine patch, nicotine gum, nicotine nasal spray, nicotine inhaler
* Drug: Varenicline or bupropion
* Behavioral: Contingency Management


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: HIV positive; >= 18 years old Receiving HIV care at Yale-New Haven Hospital, Mount Sinai Hospital, or SUNY Downstate STAR clinic; Have smoked >= 100 cigarettes in lifetime; Currently smokes some days or every day; Smokes, on average, >= 5 cigarettes per day; Able to provide written informed consent. Exclusion Criteria: Using only non-cigarette nicotine products (i.e., e-cigs, Juul, etc.); Currently using NRT, VAR, or bupropion (defined as use in the prior 7 days); Self-report or urine testing confirming pregnancy, nursing, or trying to conceive; Life-threatening or unstable medical, surgical, or psychiatric condition; Inability to provide at least one collateral contact (family member or friend); Living out of state; Unable to read or understand English (except at Mount Sinai site).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Sequential multiple assignment randomized trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 12 wks NRT+CM / 12 wks NRT+CM<br>Nicotine replacement therapy combined with contingency management. Responders remain on same treatment for second 12 weeks. | Drug: Nicotine patch, nicotine gum, nicotine nasal spray, nicotine inhaler<br>* Participants will be prescribed both long-acting and short-acting nicotine replacement therapy.<br>Behavioral: Contingency Management<br>* Participants will be financially rewarded for abstinence to tobacco.<br>|
| Experimental: 12 wks NRT+CM/ 12 wks VAR or bupropion+CM<br>Nicotine replacement therapy combined with contingency management. Non-responders switch to varenicline or bupropion combined with contingency management for second 12 weeks. | Drug: Nicotine patch, nicotine gum, nicotine nasal spray, nicotine inhaler<br>* Participants will be prescribed both long-acting and short-acting nicotine replacement therapy.<br>Drug: Varenicline or bupropion<br>* Participants will be prescribed varenicline (Chantix) or bupropion (Wellbutrin).<br>Behavioral: Contingency Management<br>* Participants will be financially rewarded for abstinence to tobacco.<br>|
| Experimental: 12 wks NRT+CM/12 wks NRT+CM plus<br>Nicotine replacement therapy combined with contingency management Non-responders switch to nicotine replacement therapy combined with intensified contingency management for second 12 weeks. | Drug: Nicotine patch, nicotine gum, nicotine nasal spray, nicotine inhaler<br>* Participants will be prescribed both long-acting and short-acting nicotine replacement therapy.<br>Behavioral: Contingency Management<br>* Participants will be financially rewarded for abstinence to tobacco.<br>|
| Experimental: 12 wks NRT/ 12 wks NRT<br>Nicotine replacement therapy alone. Responders remain on nicotine replacement therapy. | Drug: Nicotine patch, nicotine gum, nicotine nasal spray, nicotine inhaler<br>* Participants will be prescribed both long-acting and short-acting nicotine replacement therapy.<br>|
| Experimental: 12 wks NRT/ 12 wks VAR or bupropion<br>Nicotine replacement therapy alone. Non-responders switch to varenicline or bupropion alone for second 12 weeks. | Drug: Nicotine patch, nicotine gum, nicotine nasal spray, nicotine inhaler<br>* Participants will be prescribed both long-acting and short-acting nicotine replacement therapy.<br>Drug: Varenicline or bupropion<br>* Participants will be prescribed varenicline (Chantix) or bupropion (Wellbutrin).<br>|
| Experimental: 12 wks NRT/ 12 wks NRT+CM<br>Nicotine replacement therapy alone. Non-responders switch to nicotine replacement therapy combined with contingency management for second 12 weeks. | Drug: Nicotine patch, nicotine gum, nicotine nasal spray, nicotine inhaler<br>* Participants will be prescribed both long-acting and short-acting nicotine replacement therapy.<br>Behavioral: Contingency Management<br>* Participants will be financially rewarded for abstinence to tobacco.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self reported reduction in average cigarettes smoked per day at 24 weeks | Self reported reduction in average cigarettes smoked per day | 24 weeks from baseline | 
| Self reported reduction in average cigarettes smoked per day at 12 weeks | Self reported reduction in average cigarettes smoked per day | 12 weeks from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VACS index 2.0 | A validated measure of morbidity and mortality | 24 weeks from baseline | 
| CD4 Count | Median CD4 count adjusting for baseline | 24 weeks from baseline | 
| HIV Viral Load | The proportion of participants with HIV viral load suppression. | 24 weeks from baseline | 
| eCO confirmed smoking abstinence at 24 weeks | smoking abstinence confirmed by exhaled carbon monoxide | 24 weeks from baseline | 
| eCO confirmed smoking abstinence at 12 weeks | smoking abstinence confirmed by exhaled carbon monoxide | 12 weeks from baseline |