Design considerations for a pilot trial using a novel approach for evaluating smoking-cessation medication in methadone-maintained smokers

Contemp Clin Trials. 2016 Mar;47:334-9. doi: 10.1016/j.cct.2016.02.008. Epub 2016 Mar 2.

Abstract

The prevalence of smoking in methadone-maintained (MM) patients is over 80% and smoking-abstinence rates are strikingly low, even with the use of first-line smoking-cessation medications. Research has found that cigarettes increase the reinforcing properties of methadone; this interaction may be an additional, daily, challenge to smoking cessation in MM-smokers. This paper describes a novel approach in which patients who experience a particular barrier to achieving smoking abstinence are selected, and the impact of smoking-cessation medications on the identified barrier is evaluated. This is a 7-week, outpatient, randomized, within-subject, placebo-controlled, crossover trial with a follow-up visit at week 8. MM-smokers, who smoke ≥40% of their total daily cigarettes in the 4-h post-methadone-dosing period, as assessed with a Quitbit electronic cigarette lighter, will be recruited from a methadone program in Cincinnati, Ohio. Eligible participants will be randomized to receive four interventions (nicotine nasal spray (1mg per dose, up to 40 times per day), placebo nicotine nasal spray, varenicline (2mg/day), and varenicline placebo) in one of four orders to mitigate potential order effects. The primary outcome analysis will consist of two sets of statistical analyses, one comparing the effect of nicotine nasal spray to its placebo, and one comparing the effect of varenicline to its placebo, on the proportion of daily cigarettes smoked during the 4-h post-methadone-dosing period. This trial is of interest both as an efficient, precision-medicine-based approach to testing smoking-cessation interventions and as a specific strategy for identifying effective smoking-cessation treatment for MM-smokers.

Keywords: Methadone; Nicotine replacement; Opioid; Precision medicine; Smoking; Varenicline.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Analgesics, Opioid / therapeutic use*
  • Clinical Protocols
  • Cross-Over Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Methadone / therapeutic use*
  • Middle Aged
  • Nicotinic Agonists / therapeutic use
  • Opiate Substitution Treatment*
  • Opioid-Related Disorders / complications
  • Opioid-Related Disorders / drug therapy*
  • Pilot Projects
  • Research Design
  • Single-Blind Method
  • Smoking / drug therapy*
  • Smoking Cessation / methods*
  • Tobacco Use Cessation Devices
  • Treatment Outcome
  • Varenicline / therapeutic use
  • Young Adult

Substances

  • Analgesics, Opioid
  • Nicotinic Agonists
  • Methadone
  • Varenicline