Transforming the Treatment of Tobacco Use in Health Care: Seizing the Potential of the Electronic Health Record to Deliver Comprehensive Chronic Care Treatment for Smoking. This study, funded by an R35 grant to Dr. Michael Fiore, is designed to overcome barriers to effective treatment of smokers in the primary care setting. One of the major obstacles to smoking cessation is the lack of treatment effectiveness. Researchers believe that this lack of effectiveness is largely due to two factors:
This research is intended to address this deficit by developing and applying innovative, efficient, and powerful research methods to translate efficacious treatments into clinical use. This study will focus on the treatment effectiveness obstacle by piloting a potentially more powerful combination of two of the most effective pharmacotherapies: varenicline plus combination nicotine replacement therapy (NRT) treatment. Data from this pilot study will help inform the design of future studies that would use this combination treatment as a cessation tool within the chronic care arsenal of treatments. August 2015-July 2022. Funded by NCI of NIH. Dr. Michael Fiore, PI.
Exhale Study. (Status: Recruiting and seeing patients) As the federal government considers how to regulate electronic cigarettes (e-cigs), the University of Wisconsin has been awarded a $3.7 million, 5-year grant from National Cancer Institute (NCI) and FDA to study them over the next five years. This research will provide in-depth, longitudinal information, based on real-time reports, which will address key priorities that may inform regulatory and health concerns, including understanding the relations between vaping and nicotine dependence; changes in rates of smoking conventional cigarettes; health outcomes such as evidence of exposure to carcinogens, as well as acute and long-term pulmonary health; attempts to quit smoking and the success of those attempts. Specifically, researchers will identify and follow over time 150 participants who exclusively smoke cigarettes and 250 participants who both smoke and vape. Researchers will use smart phones and other tools to collect information on patterns of use of these products, levels of addiction, withdrawal symptoms, success quitting versus relapse, lifestyle factors, carcinogen exposure, and how one group of participants compares to the other over time. This research will provide essential information to inform regulatory bodies, as well as researchers, clinicians, and tobacco users, about the patterns of real-world e-cig use and how such use is related to conventional smoking and the health risks caused by it. March 2015–February 2020, $3.7 million. Funded by NCI of NIH, and FDA. Dr. Megan Piper and Dr. Douglas Jorenby, PIs.
Breaking Addiction to Tobacco for Health (BREATHE). (Status: Recruiting and seeing patients) UW-CTRI has received a $12 million 5-year grant from NCI of NIH. The grant will fund research designed to test new phased-based treatments to help patients in the Milwaukee and Madison areas quit smoking. Partners in this research include colleagues from Penn State University and the University of Illinois-Chicago, as well as Aurora Health Care, Dean Health System, and Epic. Under the BREATHE project, any smoker who visits a participating clinic, regardless of the initial reason for the visit, is invited to get treatment through BREATHE. This study implements both an EHR system that increases smokers' recruitment into treatment as well as a highly effective chronic-care treatment with intervention components for all smokers. First, the EHR system will be implemented in 18 clinics in 2 health-care systems and experimentally evaluated on its ability to increase the recruitment of smokers into chronic-care treatment (Project 1). Then, using highly efficient research methods, researchers will experimentally compare multiple intervention components and identify especially effective interventions for every phase of smoking treatment. This package of components will: increase quitting motivation amongst smokers initially unwilling to quit and prepare them for cessation (Project 2), enhance quitting success and prevent relapse when smokers are ready to quit (Project 3), and re-engage relapsed smokers in treatment and restore their abstinence (Project 4). Our highly integrated research projects will thus implement a powerful new EHR strategy to efficiently recruit primary-care patients who smoke into chronic-care treatment. BREATHE researchers will combine data from all projects and produce an optimized comprehensive chronic-care treatment for smoking that can be readily implemented in primary-care settings by project end. Thus, this research will simultaneously advance both smoking treatment and treatment research methods. June 2014-July 2019, $12 million. Funded by NCI. Michael Fiore and Tim Baker, PIs.
PTSD and Veterans Merit Award. (Status: Recruiting and seeing patients) UW-CTRI Researcher Dr. Jessica Cook has reached a major career milestone, receiving a merit award from the VA. The primary objective of her research is to produce an empirically validated treatment that increases smoking cessation in veterans with posttraumatic stress disorder (PTSD), one that can be easily integrated into smoking cessation clinics and/or mental health clinics within VA facilities. PTSD is highly prevalent in the VA patient population and is associated with a rate of smoking (53% - 66%) that far exceeds that of VA enrollees in general (22%). PTSD is also associated with unusually high rates of smoking-cessation-treatment failure. The disparity in smoking cessation outcomes amongst veterans with PTSD may occur because standard smoking cessation treatment does not address PTSD-specific vulnerabilities. Veterans with smoking-PTSD comorbidity may respond better to treatment that addresses their PTSD and associated affective symptoms, because such symptoms can both reinforce smoking and undermine quit attempts. Recent evidence shows that behavioral activation therapy (BA), a behavioral treatment that increases engagement in reinforcing activities, significantly reduces PTSD symptoms. BA may improve smoking cessation outcomes amongst veterans with PTSD because it reduces overall PTSD symptom severity and affective distress (low positive affect, high negative affect), which can cause smoking relapse. The funded research will determine whether BA, as an adjunct to standard smoking cessation treatment, (ST+BA) is superior to a comparably intense combination of standard smoking cessation treatment + health and smoking education (ST+HSE) in improving smoking cessation outcomes among veterans with PTSD. The HSE intervention is intended to constitute a credible intervention that controls for contact time. Secondary objectives are to determine if BA improves PTSD symptomatology and associated affective distress, and to identify potential mediators of BA on smoking outcomes. A total of 120 veterans with PTSD who are motivated to quit smoking will attend an initial diagnostic and baseline assessment session. Those who are interested, eligible, and who provide consent will be randomly assigned to receive ST+BA or ST+HSE and will be contacted by their individual study therapist to schedule the first treatment session. Participants will be stratified into treatment groups based on: 1) Major depressive disorder (MDD; present versus absent), and 2) PTSD symptom severity. All participants will receive eight individual sessions of ST+BA or ST+HSE. All participants will receive 20 minutes of identical standard smoking cessation treatment in each of the eight sessions. Those in the ST+BA condition will receive an additional 30 minutes of behavioral activation therapy; those in the ST+HSE condition will receive an additional 30 minutes of health education and information about smoking. All participants will receive 8 weeks of the nicotine patch. Smoking cessation outcomes will be assessed 2, 4, 8, 16, and 26 weeks after the quit date. This research has important clinical and public health significance because smoking is especially common among veterans with PTSD, and it is the leading preventable cause of disease and disability. Reducing smoking rates among veterans with PTSD would result in substantially lower smoking-related illness and death in this vulnerable group of smokers. It would also reduce tobacco-related health-care costs charged to the VA. The grant will support a researcher and a study counselor. Jan. 2014-Sept. 2019, $770,500. Funded by the VA. Jessica Cook, PI.
Clinical Relevance of Stress Neuroadaptation in Tobacco Dependence. (Recruiting and seeing patients) The broad goals of this research were to identify the origin of biomarkers related to how the body compensates for the presence of cigarette chemicals so that it can continue to function. Dr. John Curtin of UW Psychology was the principal investigator, while Dr. Megan Piper of UW-CTRI was a co-investigator on this RO1 grant. It examined stress neuroadaptation in the laboratory via startle potentiation during uncertain threats among nicotine-deprived smokers versus non-deprived smokers and non-smokers. Smokers were subsequently assigned to one of three smoking-cessation treatment conditions and reported on episodic stressors, negative feelings, smoking urge, and tobacco consumption in real time from their regular environments via smart phones or other digital devices that prompted them to enter data. Treatment outcomes were assessed at four weeks and end of treatment. Researchers evaluated the impact of this stress neuroadaptation on smokers’ feelings, urge, and tobacco consumption during smoking-cessation treatment. They examined whether first-line pharmacotherapies could dilute the influence of this stress neuroadaptation on smoking-cessation outcomes. August 1, 2012-June 30, 2017. Funded by National Institute on Drug Abuse (NIDA) of NIH. Dr. John Curtin, PI. Dr. Tim Baker and Dr. Megan Piper, Co-I’s.
Genetically Informed Smoking Cessation Trial. (Status: Recruiting patients) This randomized clinical trial is the first genetic study to look at nicotine replacement therapy (NRT) vs. varenicline head-to-head, and how participants with different genetics respond to the medications. Led by Dr. Li-Shiun Chen with collaboration from UW-CTRI Research Director Dr. Tim Baker and UW-CTRI Director of Clinical Services Dr. Doug Jorenby, the researchers hope to determine whether genetic markers can be used to optimize smoking cessation pharmacotherapy to enhance efficacy, medication adherence, and reduce side effects. The researchers’ recent work, which suggests that the nicotinic receptor gene CHRNA5 alters the response to NRT, has been replicated in a meta-analysis. New preliminary data suggest that CHRNA5 may be a useful marker for medication choice, because patients with CHRNA5 variant rs16969968 AA/GA genotypes may benefit from NRT and those with GG genotypes (conferring poor response to NRT) may benefit from varenicline, a medication with higher cost and use restrictions. Similarly, other genetic variation such as the nicotine metabolism gene CYP2A6 also alters response to NRT. Currently, there is insufficient evidence to support the clinical use of genotype-based smoking-cessation treatment, because these findings are based on retrospective pharmacogenetic analyses of different trials with markedly different placebo and counseling effect sizes and dissimilar designs. For clinical translation, we need head to head comparison of state-of-the-art interventions, use of key genotypes implicated by current research, and valid assessments of side effects and adherence. This study of 720 smokers uses a stratified randomization trial design based on a subject's pertinent genotype for smoking cessation. Specifically, in Aim 1, researchers will determine if CHRNA5 genotype moderates the effect of medication (combination NRT, varenicline, vs. placebo) on abstinence. In Aim 2, researchers will determine if CHRNA5 genotype predicts medication adherence and side effects. In Aim 3, researchers will incorporate multiple genotypes and other predictors in order to develop a clinical treatment assignment algorithm for cessation success. This work could result in improved physician care of patients who smoke, overall smoking cessation success, and prevention of cancer, heart, and lung disease. Sept. 2014-July 2019, $90,000. Funded by NIH. Li-Shiun Chen, PI. Douglas Jorenby, co-PI.
Integrating Genetics, Adverse Events, and Adherence to Improve Smoking Cessation. (Status: Data under analysis for dissemination) Using data from the Wisconsin Smokers’ Health Study, the goal of this project is to identify genetic associations to adverse events arising from pharmacological treatments for smoking cessation and examine how genetics, adverse events, and medication adherence jointly impact the efficacy of pharmacological treatments for smoking cessation. The results could lead to individually tailored treatments that decrease adverse events and increase successful cessation. April 2015-March 2017, $34,000. Funded by NIH. Robert Culverhouse, PI. Megan Piper, co-I.
Primary Care Research Fellowship. Dr. Kristin Berg is a Primary Care Research Fellow, supported by a National Research Service Award (T32 Postdoctoral Training Grant) from the Health Resources and Services Administration to the University of Wisconsin Department of Family Medicine and Community Health. July 2015-June 2017. Funded by the Health Resources and Services Administration. Dr. David Rabago, PI.
Wisconsin Smokers Health Study 2 (WSHS 2). (Status: Recruitment complete, year 1 outcome data analyses underway, participants are finishing up Year 3 final visits) UW-CTRI was awarded a $10-million 5-year National Heart, Lung, and Blood Institute (NHLBI) grant to discover the best ways to help Wisconsin residents stop smoking. The new study essentially extended the Wisconsin Smokers’ Health Study and is known as WSHS 2. It included potentially life-saving tests—including artery scans that can signal impending risk of a stroke or heart attack—free of charge. Participants got free coaching and medications to help them quit smoking. Drs. Mike Fiore, Tim Baker, and James Stein (of UW Preventive Cardiology) have been the lead researchers for this grant. The original Smoker’s Health Study (WSHS), launched in 2004, revealed how quitting smoking affects nearly every part of a person’s health, lifestyle, and well-being. Many patients from WSHS continued participation in WSHS 2, and their participation will culminate in health data spanning 10 years. The media announcement of WSHS 2 garnered 2,500 volunteers. The Center recruited smokers as new study participants for WSHS 2. In addition, everyone from the previous study—whether now smoking or not—was invited to continue their participation. In total, 1,500 individuals will participate in WSHS 2. Each participant got assistance from a personal quit coach—something many former smokers say is essential because they felt that giving up cigarettes was like “losing my best friend.” The quit coach was a familiar face who ensures that the patient doesn’t feel like s/he is going through the process alone. All participants were compensated for time and travel. Each individual participant received test results, such as cholesterol levels, artery scans, blood counts, and diabetes tests. These results could signal imminent trouble and save lives. The study employed medical tests—such as carotid artery ultrasound scans and arterial tonometry—to determine how quitting smoking improved health over time, and how continuing to smoke harmed health. These tests concentrated on cardiovascular disease, but also targeted conditions such as lung disease and diabetes mellitus. While it was well known that smoking is very dangerous, researchers knew less about how quitting (versus continued smoking) affected health. Every participant received state-of-the-art active medication: 1) varenicline or 2) nicotine patch + nicotine lozenge or 3) just nicotine patch. WSHS 2 researchers have found that the three treatment options helped about the same percentage of participants (1 out of 4) to quit smoking 6 months after the quit date. These results were published in the Journal of the American Medical Association (JAMA). At the end of this study, the researchers hope to enhance knowledge of how to treat smoking optimally, as well as how quitting smoking helps participants to reduce their risk of heart disease, stroke, and cancer, and the mechanisms by which these health benefits occur. Sept. 2011-Nov. 2017, $10 million. Funded by NHLBI. Dr. Tim Baker, Dr. Michael Fiore, Dr. Jim Stein, PIs.