Naltrexone and Varenicline: Weight Gain and Tolerability in Cigarette Smokers
Condition: Smoking; Nicotine Dependence
MeSH terms: Weight Gain; Tobacco Use Disorder
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this study is to determine whether the combination of naltrexone (Depade) and
      varenicline (Chantix) minimizes post-smoking cessation weight gain and how well the
      combination is tolerated.
    

Detailed description: 
      Varenicline, a medication recently approved by the FDA, results in smoking cessation rates as
      high as 50%, significantly better than bupropion or placebo. However, varenicline does not
      reduce post-cessation weight gain, so weight concerns may keep some smokers from taking
      advantage of this effective therapy.

      A potential solution would be to combine varenicline with an agent that reduces weight gain.
      In this regard, several studies have shown that naltrexone reduces weight gain (O'Malley et
      al., 2006; Toll et al., 2007).

      This effect appears to be dose dependent, favoring lower doses (i.e., 25 mg daily). Thus, the
      proposed study seeks to conduct a pilot clinical trial of low dose naltrexone (25 mg daily)
      compared to placebo for minimizing weight gain in combination with varenicline for smoking
      cessation. Forty individuals who smoke at least 10 cigarettes per day will receive open-label
      varenicline for 12 weeks according to the recommended titration schedule up to 1 mg
      varenicline twice daily. Subjects will be randomized to receive either placebo or 25 mg
      naltrexone daily, with treatment starting at the quit date (after 1 week on varenicline to
      minimize nausea, a side effect of both varenicline and naltrexone) and continuing for 11
      weeks. Subjects will take 12.5 mg naltrexone daily for the first week and 25 mg naltrexone
      daily for the next 10 weeks of treatment. In an effort to uncover mechanisms for naltrexone's
      weight suppressant effects, an experiment will be conducted using food odors and food
      consumption to examine naltrexone's effects on palatability, incentive value, and
      alliesthesia.

      This experiment will be conducted pretreatment and after 2 weeks on naltrexone. The primary
      aim of this pilot study is to examine weight gain in participants who complete the clinical
      trial treatment. Weight gain for those who are continuously abstinent for the last 4 weeks of
      treatment and rates of adverse events will be secondary outcomes. The effects of naltrexone
      on odor/food palatability, incentive value, and alliesthesia will be exploratory outcomes.
      Effect size estimates for weight gain will be generated for a NIH grant application.
    

Intervention name(s): Naltrexone; Varenicline
Intervention type(s): Drug; Drug
Intervention description(s): Varenicline (Chantix) 1 mg oral tablet twice per day + naltrexone 25 mg oral capsule once per day; Arm 1 (Experimental) = Varenicline (Chantix) 1 mg oral tablet twice per day + naltrexone 25 mg oral capsule once per day; Arm 2 (Placebo Comparator) = Varenicline (Chantix) 1 mg oral tablet twice per day + placebo naltrexone 25 mg oral capsule once per day
Other intervention name(s): Chantix
Intervention MeSH terms: Naltrexone; Varenicline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Tobacco; Smoking; Weight; Naltrexone; Varenicline