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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Tobacco Use Cessation
• Intervention / Treatment: Drug: Nicotine patch, nicotine gum, nicotine nasal spray, nicotine inhaler; Drug: Varenicline or bupropion; Behavioral: Contingency Management

Detailed Description

Using a Sequential Multiple Assignment Randomized Trial (SMART) design, this project is a two-arm, two-stage randomized trial of 320 adult PWH who smoke cigarettes and receive care in one of three health systems (targeted enrollment changed from 632 to 320 with NCI approval and IRB protocol amendment). 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] or collateral verification) 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 self-reported abstinence at 24 weeks post-enrollment (primary outcome changed from eCO-confirmed abstinence to self-reported abstinence with NCI approval and IRB protocol amendment). The specific aims of the proposed study are to: (1) identify the optimal adaptive approach to promote reduced tobacco use (changed from eCO-confirmed smoking abstinence with NCI approval and protocol amendment) (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.

• Study Type: Interventional
• Enrollment (Estimated): 320
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: June-Marie Weiss, MA, MEd; Phone Number: 203-737-3347; Email: junemarie.weiss@yale.edu

Study Locations

• United States
  • Connecticut
    • Bridgeport, Connecticut, United States, 06110
      • Bridgeport Hospital Infectious Disease Clinic
    • New Haven, Connecticut, United States, 06510
      • Yale University School of Medicine
  • New York
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate STAR Clinic
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• HIV positive;
• >= 18 years old
• Receiving HIV care at Yale-New Haven Hospital, Bridgeport 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 12 wks NRT+CM / 12 wks NRT+CM; 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; Participants will be prescribed both long-acting and short-acting nicotine replacement therapy.; Behavioral: Contingency Management; Participants will be financially rewarded for abstinence to tobacco.
Experimental: 12 wks NRT+CM/ 12 wks VAR or bupropion+CM; 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; Participants will be prescribed both long-acting and short-acting nicotine replacement therapy.; Drug: Varenicline or bupropion; Participants will be prescribed varenicline (Chantix) or bupropion (Wellbutrin).; Behavioral: Contingency Management; Participants will be financially rewarded for abstinence to tobacco.
Experimental: 12 wks NRT+CM/12 wks NRT+CM plus; 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; Participants will be prescribed both long-acting and short-acting nicotine replacement therapy.; Behavioral: Contingency Management; Participants will be financially rewarded for abstinence to tobacco.
Experimental: 12 wks NRT/ 12 wks NRT; Nicotine replacement therapy alone. Responders remain on nicotine replacement therapy.	Drug: Nicotine patch, nicotine gum, nicotine nasal spray, nicotine inhaler; Participants will be prescribed both long-acting and short-acting nicotine replacement therapy.
Experimental: 12 wks NRT/ 12 wks VAR or bupropion; 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; Participants will be prescribed both long-acting and short-acting nicotine replacement therapy.; Drug: Varenicline or bupropion; Participants will be prescribed varenicline (Chantix) or bupropion (Wellbutrin).
Experimental: 12 wks NRT/ 12 wks NRT+CM; 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; Participants will be prescribed both long-acting and short-acting nicotine replacement therapy.; Behavioral: Contingency Management; Participants will be financially rewarded for abstinence to tobacco.

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of Barriers and Facilitators	Using a Hybrid Effectiveness-Implementation Type I design, identify barriers and facilitators to delivering our intervention to inform future implementation.	Baseline and Up to 4 years

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Steven Bernstein, MD, Dartmouth College; Principal Investigator: E. Jennifer Edelman, MD, MHS, Yale University

Publications and helpful links

General Publications

• Edelman EJ, Dziura J, Deng Y, Bold KW, Murphy SM, Porter E, Sigel KM, Yager JE, Ledgerwood DM, Bernstein SL. A SMARTTT approach to Treating Tobacco use disorder in persons with HIV (SMARTTT): Rationale and design for a hybrid type 1 effectiveness-implementation study. Contemp Clin Trials. 2021 Nov;110:106379. doi: 10.1016/j.cct.2021.106379. Epub 2021 Mar 29.

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2020
• Primary Completion (Estimated): November 30, 2024
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: July 22, 2020
• First Submitted That Met QC Criteria: July 25, 2020
• First Posted (Actual): July 28, 2020

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Enzyme Inhibitors; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Cytochrome P-450 Enzyme Inhibitors; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Dopamine Uptake Inhibitors; Nicotine; Bupropion; Varenicline
• Other Study ID Numbers: 2000026332; R01CA243910 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No