Clinical trial NCT01553084: A Comparative Effectiveness & Long Term Health Study in Wisconsin Smokers
Official title: A Comparative Effectiveness & Long Term Health Study in Wisconsin Smokers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Smoking Cessation
Smoking
Nicotine Dependence
Keywords: Smoking Cessation
Smoking
Nicotine
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2012-03-13
Enrollment: 1086
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The overall purpose of this research is two-fold. First, the two smoking cessation medication treatments with the strongest evidence of effectiveness have never been directly compared. This research will determine how these two treatments compare in effectiveness in a head-to-head trial, and which types of smokers benefit most from each. Second, much of the data on smoking and health come from studies from many years ago. Today's smokers differ from earlier smokers in many ways that could influence the impact of smoking on health (e.g., weight, sex, diet, socio-economic status); the proposed work will determine how smoking cessation affects cardiovascular and pulmonary health in today's smokers.

Detailed description: The proposed study will recruit and treat a large sample of contemporary smokers and former smokers at an age of increasing health risk, to achieve the following over-arching aims that are important to the NHLBI mission:

* Specific Aim 1: Produce important new data on how to treat smoking optimally by conducting an open label comparative effectiveness trial (CET) that for the first time directly contrasts the two smoking cessation pharmacotherapies with the strongest extant evidence of efficacy: combination NRT and varenicline.
* Specific Aim 2: Determine the impact of smoking cessation on biomarkers and health risk factors, especially those relevant to CVD, in today's smokers, which will elucidate the mechanisms via which cessation benefits health.
* Specific Aim 3: Identify which individuals are at greatest risk for exacerbation of biomarkers or risk factor status due to continued smoking, and who will benefit most from cessation. This will help identify individuals who are most in need of cessation intervention. While all smokers need to quit, this evidence could ultimately be used to help focus treatment and motivate smokers and clinicians to intervene more intensively with patients at greatest risk.

Two secondary aims are to use the results of Primary Aim 1 to develop a treatment assignment algorithm for the optimal treatment of today's smokers and to use the results from Primary Aim 2 to determine the relation of health biomarkers to clinically meaningful disease outcomes such as CVD events.

We will re-recruit as many smoking and non smoking participants from our past longitudinal cohort study("Wisconsin Smokers' Health study"; NCT01122238) in 2004. We will then recruit additional smokers to participate in the comparative effectiveness trial and join the longitudinal cohort..

All participants who enroll will complete questionnaires about their demographics, smoking history, withdrawal symptoms, affect, alcohol use, stressors, medication usage and diet. They will also complete a structured clinical interview to assess mental health. They will provide blood samples for testing of various markers of cardiovascular disease and risk as well as for genetics testing. They will all have carotid ultrasounds, pulmonary function tests, arterial tonometry assessments, and 12-lead ECGs. Participants in Madison will also have a treadmill stress test. Participants will wear a pedometer for 1 week and record the daily number of steps. Participants will provide permission for staff to review their medical charts to assess smoking-relevant diagnoses and treatment. These assessments will occur at baseline and again 3 years later. A smaller subset of these assessments will also be conducted 1 year after enrollment. Participants will also complete brief phone assessments at 6-month intervals up to the 3-year visit.

Interested and eligible smoking participants from the original cohort study and all newly recruited participants will enroll in a new smoking cessation intervention study. Participants in the cessation treatment study will be randomly assigned to receive the nicotine patch, nicotine patch + nicotine lozenge or varenicline. If the participant from the original cohort study is not eligible to use all study medications but is otherwise eligible for cessation treatment, s/he will be assigned to a non-randomized treatment arm and will receive nicotine patch (if appropriate). All cessation participants will receive 6 individual counseling sessions.

Eligibility criteria: We are only recruiting by invitation only (to members of our past cohort). We will open up enrollment to the public in the Madison, WI and Milwaukee WI areas at the end of 2012.

Inclusion Criteria:

a. To be eligible for the Comparative effectiveness trial, participants must:

* smoke 5 or more cigarettes per day,
* desire to quit smoking but not be currently engaged in cessation treatment,
* be medically eligible to use either combination NRT or varenicline,
* have reliable phone access,
* if female, must not be pregnant and must be willing to use an acceptable birth control method.

Exclusion Criteria:

1. There are no exclusion criteria for participating in the main health outcomes study, other than being unwilling to complete study assessments.
2. All smoking participants from new and original cohorts will be excluded from the cessation trial for the following reasons:

   * end-stage renal disease with hemodialysis;
   * prior suicide attempts within the last 5 years or current suicidal ideation;
   * diagnosis of and/or treatment for schizophrenia;
   * other psychotic disorders or bipolar disorder within the last 10 years;
   * current PHQ-9 score indicative of moderately severe depression;
   * severe untreated hypertension \>200/100 mmHg;
   * currently taking Wellbutrin, Zyban or bupropion;
   * hospitalized for a stroke, heart attack, congestive heart failure or diabetes within the last year;
   * used pipe tobacco, cigars, snuff or chew more than twice in the past week.

It should be noted that if any incidental findings appear in any of the cardiology tests (e.g., ultrasound, tonometry, ECG, or exercise stress test; see forms in Supplemental Information section of application), the study cardiologist (Dr. Stein or his designee) will be assign the participant to the non-randomized treatment arm and they will be given the nicotine patch and the same counseling intervention as CET participants. They will not be included in the CET analyses. This will be done to properly address the cardiovascular risk warning from the FDA regarding varenicline (Chantix).

Primary outcomes:
measure: Biochemically-confirmed 7-Day Point-Prevalence Abstinence at 26 Weeks
timeFrame: Assessed 26 weeks after the target quit day.
Secondary outcomes:
measure: Number of Days to Relapse
timeFrame: Assessed from the target quit day through 26 weeks.
measure: Number of Participants With Initial Cessation in the First 7 Days Post-quit
timeFrame: Assessed for the first seven days after the target quit date.
measure: The Effects of Quitting Smoking vs. Continued Smoking on Change in Carotid Intima-media Thickness (CIMT).
timeFrame: Assessed at Baseline and Year 3
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin Center for Tobacco Research and Intervention, School of Medicine and Public Health
state: Wisconsin
city: Milwaukee
country: United States
facility: University of Wisconsin Center for Tobacco Research and Intervention, School of Medicine and Public Health
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Michael C Fiore, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Wisconsin, Madison
name: James H Stein, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Baker TB, Piper ME, Stein JH, Smith SS, Bolt DM, Fraser DL, Fiore MC. Effects of Nicotine Patch vs Varenicline vs Combination Nicotine Replacement Therapy on Smoking Cessation at 26 Weeks: A Randomized Clinical Trial. JAMA. 2016 Jan 26;315(4):371-9. doi: 10.1001/jama.2015.19284.
citation: Karim R, Xu W, Kono N, Sriprasert I, Li Y, Yan M, Stanczyk FZ, Shoupe D, Mack WJ, Hodis HN. Effect of menopausal hormone therapy on arterial wall echomorphology: Results from the Early versus Late Intervention Trial with Estradiol (ELITE). Maturitas. 2022 Aug;162:15-22. doi: 10.1016/j.maturitas.2022.02.007. Epub 2022 Mar 17.
citation: Kaye JT, Johnson AL, Baker TB, Piper ME, Cook JW. Searching for Personalized Medicine for Binge Drinking Smokers: Smoking Cessation Using Varenicline, Nicotine Patch, or Combination Nicotine Replacement Therapy. J Stud Alcohol Drugs. 2020 Jul;81(4):426-435. doi: 10.15288/jsad.2020.81.426.
citation: Mitchell C, Piper ME, Smith SS, Korcarz CE, Fiore MC, Baker TB, Stein JH. Changes in carotid artery structure with smoking cessation. Vasc Med. 2019 Dec;24(6):493-500. doi: 10.1177/1358863X19867762. Epub 2019 Aug 17.
citation: Schlam TR, Baker TB, Smith SS, Cook JW, Piper ME. Anxiety Sensitivity and Distress Tolerance in Smokers: Relations With Tobacco Dependence, Withdrawal, and Quitting Successdagger. Nicotine Tob Res. 2020 Jan 27;22(1):58-65. doi: 10.1093/ntr/ntz070.