Clinical trial NCT04176172: Optimizing Tobacco Use Treatment for PLWHA
Official title: Testing Novel Pharmacogenetic and Adherence Optimization Treatments to Improve the Effectiveness of Smoking Cessation Treatments for Smokers with HIV
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: HIV/AIDS
Nicotine Dependence
Keywords: Smoking Cessation
Nicotine Dependence
HIV/AIDS
Varenicline
Nicotine Patch
Cigarette Smoking
Managed Problem Solving
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Northwestern University
First posted: 2019-11-25
Enrollment: 340
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The advent of anti-retroviral therapy (ART) for people living with HIV/AIDS (PLWHA) substantially improved life expectancy but has also led to the critical need to address modifiable risk factors associated with cancer and cardiovascular disease, such as tobacco smoking. HIV-infected smokers lose more life-years due to tobacco use than they do to their HIV infection.

There have been relatively few studies of tobacco use treatments for PLWHA and systematic reviews show that there are insufficient data to conclude that tobacco dependence interventions that are efficacious in the general population are efficacious for PLWHA. Further, many studies in this area have lacked randomization and a control group, infrequently used an intent-to-treat (ITT) approach and biological verification of tobacco abstinence, and lacked post-treatment follow-up.10 What investigators do know thus far is that behavioral interventions and the nicotine patch yield moderate effects on cessation; and 2 recent placebo-controlled trials - one in France and one by this lab - found that varenicline is safe and effective for treating tobacco use among PLWHA, but yield quit rates that are substantially lower than those reported in the general population. Thus, there is a critical need to rigorously test novel ways to optimize tobacco cessation treatment for smokers with HIV.

Detailed description: Smoking among PLWHA is a critical public health issue, with the rate of smoking 2-3 times greater than it is in the general population and the health risks of smoking outweighing those associated with the virus itself. Unfortunately, remarkably few studies have evaluated smoking cessation interventions for PLWHA and the available literature indicates that both behavioral and pharmacological smoking cessation interventions yield modest effect sizes and quit rates that are considerably lower than in the general population. A sizable literature, including studies by our research team, indicates that using the nicotine metabolite ratio (NMR) to personalize the selection of medications for tobacco use and the MAPS intervention to augment adherence to these medications can optimize treatments for tobacco use among PLWHA. The NCI recognized the potential for clinicians to use the NMR to individualize cessation treatment in order to improve effectiveness (https://www.cancer.gov/about-nci/budget/plan/public-health) and the Centers for Disease Control and Prevention (CDC) has endorsed MAPS as an evidence-based approach to increasing medication adherence among PLWHA. As such, this trial will test these intervention optimization strategies to determine if individually or together they can represent an effective approach to treating tobacco use in this under-served population of smokers. As a major advance for this area of work, the investigators will use rigorous methodology to evaluate these optimization strategies (i.e., a randomized design, biological verification, an ITT approach, and 6-month outcome assessments) and, overall, our approach is consistent with the multiphase optimization strategy (MOST) framework, which has been used to identify intervention components that maximize cessation outcomes. This trial will also assess theoretically derived and empirically based mechanisms through which these optimization strategies affect cessation and explore sub-groups who are more or less responsive to these strategies. In the end, this trial, which is consistent with the Office of AIDS Research trans-NIH Strategic Plan for HIV and HIV-Related Research (https://www.oar.nih.gov/hiv-policy-and-research/research-priorities), will determine if getting the right medication to the right person and making sure they adequately use the medication optimizes tobacco cessation treatments among PLWHA as a critical way to improve health outcomes for this population.

Eligibility criteria: Key Inclusion Criteria:

* \>18 years, smoke daily for the past 30 days
* Confirmed HIV+ (exhibit viral load of \<1000 copies/mL)
* Residing in the geographic area close to one of the sites for at least 7 months
* Able to use varenicline/TN patch safely

Key Exclusion Criteria:

* Current untreated and unstable diagnosis of substance abuse/dependence
* Current diagnosis of unstable and untreated major depression, psychosis or bipolar disorder
* Suicide risk as measured by the C-SSRS
* Current use or discontinuation within last 14 days of quit smoking medications
* Cancer, heart disease, stroke or MI within the past 6 months requires study physician approval
* Uncontrolled hypertension
* History of epilepsy or seizure disorder requires study physician approval
* Women who are pregnant, planning a pregnancy, or lactating
* Use of e-cigarettes, chewing tobacco, snuff or snus
* Generalized eczema or psoriasis
* A reaction or sensitivity to a nicotine patch or any other transdermal medication requires study physician approval
* Currently participating in a smoking cessation program

Primary outcomes:
measure: Point-prevalence abstinence
timeFrame: 26 weeks (24 weeks post target quit date)
Secondary outcomes:
measure: Six-month quit rate
timeFrame: 6 months
measure: Prolonged abstinence
timeFrame: 26 weeks (24 weeks post target quit date)
measure: Continuous abstinence
timeFrame: 26 weeks (24 weeks post target quit date)
measure: Time to 7-day relapse
timeFrame: 26 weeks (24 weeks post target quit date)
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Robert Schnoll, PhD
role: PRINCIPAL_INVESTIGATOR
References: