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

December 11, 2025 updated by: Yale University
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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 outcomes will be self-reported reduction in average cigarettes smoked per day at 24 weeks and 12 weeks (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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
323

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Self Reported Reduction in Average Cigarettes Smoked Per Day at 12 Weeks
Time Frame: Week 12
Self reported reduction in average cigarettes smoked per day at 12 weeks
Week 12
Self Reported Reduction in Average Cigarettes Smoked Per Day at 24 Weeks
Time Frame: 24 weeks
Self reported reduction in cigarettes smoked per day at 24 weeks
24 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Exhaled Carbon Monoxide (eCO) Confirmed Smoking Abstinence at 12 Weeks
Time Frame: 12 weeks from baseline
Number of participants with smoking abstinence confirmed by exhaled carbon monoxide or next closest informant verification
12 weeks from baseline
Exhaled Carbon Monoxide (eCO) Confirmed Smoking Abstinence at 24 Weeks
Time Frame: 24 weeks from baseline
Number of participants with smoking abstinence confirmed by exhaled carbon monoxide or next closest informant verification
24 weeks from baseline
VACS Index 2.0 Score
Time Frame: 24 weeks from baseline
The Veterans Aging Cohort Study (VACS) 2.0 Index is A validated measure of morbidity and mortality. It estimates risk of 5-year all-cause mortality in patients with HIV. Total score range of 0-129. A higher total score indicates a greater risk of adverse health outcomes.
24 weeks from baseline
CD4 Count
Time Frame: 24 weeks from baseline
CD4 lymphocyte cell count. Normal range is 500-1200 cells per cubic millimeter. As HIV infection progresses, CD4 count drops.
24 weeks from baseline
HIV Viral Load, Detectable
Time Frame: 24 weeks from baseline
HIV viral load greater than 200 copies per milliliter of blood and detectable on standard lab test
24 weeks from baseline

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Identification of Barriers and Facilitators
Time Frame: Baseline and Up to 4 years
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Yale University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Steven Bernstein, MD, Dartmouth College
  • Principal Investigator: E. Jennifer Edelman, MD, MHS, Yale University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 27, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 24, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 24, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 22, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 25, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 28, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 5, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 11, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings