Mobile Health Interventions for Medication Adherence Among PLWH

Study Overview
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Brief Summary
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Cigarette smoking remains highly prevalent among persons living with HIV (PLWH). Quitting smoking can have important health benefits for this population. However, PLWH have historically had a difficult time quitting smoking. This is likely due, at least in part, to poor medication adherence. Poor adherence to medication is a well-documented issue among PLWH. Research shows that not taking smoking cessation medications as prescribed can limit their treatment effectiveness. Improving adherence to smoking cessation medications will likely increase smoking cessation attempt success. Mobile phone applications and behavioral interventions show promise for improving adherence to smoking cessation medications and cessation outcomes among PLWH. Therefore, this trial will assess 1) whether a mobile phone application is a feasible and acceptable intervention for improving medication adherence; 2) whether use of the mobile phone app improves adherence to varenicline; and 3) smoking cessation outcomes.

Detailed Description
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Cigarette smoking is a significant public health problem among persons living with HIV (PLWH). The prevalence of smoking among PLWH is 40-75%, compared to approximately 15% in the general population. In PLWH, smoking confers increased risk of cardiovascular disease, respiratory conditions, lung cancer, poor adherence to antiretroviral (ARV) therapy, poor HIV treatment outcomes, and all-cause mortality. Approximately 24% of deaths among PWLH on ARV are attributable to tobacco use. Moreover, smokers with HIV lose more life years to smoking than to HIV itself (13 versus 5 years). Smoking cessation is a challenge for smokers with HIV. Smokers with HIV are interested in quitting, yet most quit attempts end in relapse. Poor cessation outcomes are likely attributable, in part, to poor adherence to smoking cessation medications. Not taking varenicline as prescribed significantly limits treatment effectiveness. Adherence to varenicline in smokers with HIV is poor, with only 56-62% of individuals in clinical trials taking the medication as prescribed. Putatively, real world adherence is expected to be lower. Medication adherence is a well-documented issue in HIV: only 62% achieve optimal adherence to ARV. Interventions are needed to improve smoking cessation medication adherence among smokers with HIV. Such interventions will improve cessation and reduce the burden of smoking in this population. Mobile phone-delivered interventions show promise for improving cessation outcomes in smokers living with HIV. However, an intervention that provided text message medication reminders and motivational cessation messages with or without phone-delivered counseling, as compared to a control group, yielded no group differences for varenicline adherence. Thus, it is possible that more intensive, and multi-component, interventions are required to improve the effectiveness of mobile-phone-based interventions. This trial will: 1) assess the feasibility and acceptability of a mobile phone app that aims to increase medication adherence; 2) whether use of the app and/or contingency management increases adherence to varenicline over varenicline treatment as usual; and 3) monitor smoking cessation outcomes.

Official Title
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Mobile Health Interventions for Varenicline Adherence Among HIV-positive Smokers

Conditions
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HIV/AIDS, Smoking, Smoking Cessation, HIV

Intervention / Treatment
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* Drug: Varenicline
* Device: Mobile phone application
* Behavioral: Contingency management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between the ages of 18-65 HIV-positive Currently engaged with an HIV care provider Interested in quitting smoking within the next 30 days Has an Android (v5.x.x or Lollipop) or iOS (v6.0) smartphone (interested participants without a compatible smartphone will be provided one, with costs offset by the study team) English-speaking Capable of giving written informed consent Exclusion Criteria: Inability to attend study sessions Any medical condition or concomitant medication that could compromise participant safety or treatment, as determined by the Principal Investigator, Study Physician, and/or participant's HIV care provider Current use of nicotine replacement therapy or other smoking cessation treatment (e.g., bupropion) Pregnant, planning to become pregnant, nursing, or becoming pregnant during the study BAL >0.000 at screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Parallel Assignment
Interventional Model Description: Participants will be assigned to one of three study conditions: 1) varenicline alone; 2) varenicline + mobile health app; 3) varenicline + mobile health app + contingency management
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Varenicline<br>An α4β2 nicotinic acetylcholine receptor partial agonist | Drug: Varenicline<br>* All participants will receive a standard 12-week course of varenicline tartrate. Participants will receive 0.5 mg tablets per oral (PO) once daily for days 1-3, 0.5 mg tablets PO twice daily for days 4-7, and 1 mg tablets PO twice daily for days 8-84<br>* Other names: Chantix;|
| Experimental: Varenicline + mobile app<br>An α4β2 nicotinic acetylcholine receptor partial agonist + a mobile phone application designed to improve adherence to medications | Drug: Varenicline<br>* All participants will receive a standard 12-week course of varenicline tartrate. Participants will receive 0.5 mg tablets per oral (PO) once daily for days 1-3, 0.5 mg tablets PO twice daily for days 4-7, and 1 mg tablets PO twice daily for days 8-84<br>* Other names: Chantix;Device: Mobile phone application<br>* Participants randomized to 2 of the 3 study groups will receive a mobile phone application designed to improve adherence to medication. The app has a number of functions, including: a) reminders to take medication; b) information about coping strategies for dealing with side effects and withdrawal symptoms; c) provision of a personalized graphical display of treatment progress (e.g., adherence, side effects); d) camera-based verification of having taken medication.<br>|
| Experimental: Varenicline + mobile app + contingency management<br>An α4β2 nicotinic acetylcholine receptor partial agonist + a mobile phone application designed to improve adherence to medications + monetary reinforcers for being adherent to medication | Drug: Varenicline<br>* All participants will receive a standard 12-week course of varenicline tartrate. Participants will receive 0.5 mg tablets per oral (PO) once daily for days 1-3, 0.5 mg tablets PO twice daily for days 4-7, and 1 mg tablets PO twice daily for days 8-84<br>* Other names: Chantix;Device: Mobile phone application<br>* Participants randomized to 2 of the 3 study groups will receive a mobile phone application designed to improve adherence to medication. The app has a number of functions, including: a) reminders to take medication; b) information about coping strategies for dealing with side effects and withdrawal symptoms; c) provision of a personalized graphical display of treatment progress (e.g., adherence, side effects); d) camera-based verification of having taken medication.<br>Behavioral: Contingency management<br>* Participants randomized to 1 of the 3 study groups will receive monetary reinforcement contingent upon verified medication adherence behaviors. Participants in the other 2 groups will be yoked to a participant in the CM group so that they also have a chance of earning monetary reinforcers, though not contingent upon their own behaviors.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The average number of times per day that participants initiate an interaction with mobile app | The average number of times per day that participants initiate an interaction with the app, as measured by background analytics | Daily throughout study duration (12 weeks) | 
| The average number of times per day participants respond to a prompt from mobile app | The average number of times per day that participants respond to prompts from the app, as measured by background analytics | Daily throughout study duration (12 weeks) | 
| Technical issues with using the mobile app | Average number of technical issues reported by participants throughout the course of the study | Weekly throughout study (once every week for 12 weeks) | 
| Perceived usefulness of mSMART app | Participants will be asked to respond to the following: Overall, I find the mSMART app useful for remembering to take my varenicline. Response options include: Strongly disagree; Somewhat disagree; neither agree nor disagree; somewhat agree; strongly agree. | Week 12 | 
| Perceived ease of use of mSMART app | Participants will be asked to respond to the following: Overall, I find the mSMART app easy to use. Response options include: Strongly disagree; Somewhat disagree; neither agree nor disagree; somewhat agree; strongly agree. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherence to varenicline | Percentage of varenicline pills taken as directed, as measured via pill counts | Weekly throughout study duration (once a week, over the course of 12 weeks) | 
| Concentration of expired breath carbon monoxide | Participants will provide an expired breath carbon monoxide sample at each study visit, measured in parts per million. Smoking cessation will be defined as a measured carbon monoxide sample that is ≤50% lower than their expired breath carbon monoxide that was measured at baseline | Baseline and Weekly throughout study (once every week for 12 weeks) | 
| Concentration of cotinine in urine sample | Participants will provide a urine sample at each study visit. These samples will be tested with a rapid urinary cotinine strip that indicates whether or not the participant has been abstinent from smoking (measured in ng of cotinine per mL of urine). | Weekly throughout study (once every week for 12 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Smoking, mHealth, Chantix, Varenicline, HIV