Naltrexone and Varenicline: Weight Gain and Tolerability in Cigarette Smokers
Information source: Yale University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Smoking; Nicotine Dependence
Intervention: Naltrexone (Drug); Varenicline (Drug)
Phase: Phase 1/Phase 2
Status: Completed
Sponsored by: Yale University Official(s) and/or principal investigator(s): Benjamin A. Toll, PhD, Principal Investigator, Affiliation: Yale University
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.
Clinical Details
Official title: Naltrexone and Varenicline: Weight Gain and Tolerability in Smokers
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Primary outcome: Weight Gain in Treatment Completers
Secondary outcome: Weight Gain in Participants Who Are Continuously Abstinent for the Last 4 Weeks of TreatmentTolerability of the Combination of 25 mg Naltrexone and 2 mg Varenicline
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 75 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Between the ages of 18 and 75
2. Smoking 10 or more cigarettes per day
3. Fewer than 3 months of smoking abstinence in the past year
4. Motivated to stop smoking
Exclusion Criteria:
1. Current use of opiates, and/or a urine toxicology screen positive for opiates
2. Chronic pain conditions necessitating opioid treatment (naltrexone, an opioid
antagonist will make these medications ineffective)
3. Evidence of significant hepatocellular injury as evidence by AST or ALT >3 x normal
or elevated bilirubin
4. History of cirrhosis
5. Any serious or unstable disease within 6 months
6. Seizure risk
7. Diabetes mellitus requiring insulin or oral hypoglycemic medications
8. Hepatic or renal impairment
9. Use of a monoamine oxidase inhibitor in the prior 14 days
10. Clinically significant cardiovascular disease within 6 months
11. Uncontrolled hypertension
12. Baseline systolic blood pressure higher than 150 mm Hg or diastolic blood pressure
higher than 95 mm Hg
13. Severe chronic obstructive pulmonary disease
14. History of cancer (except treated basal cell or squamous cell carcinoma of the skin)
15. History of clinically significant allergic reactions
16. Major depressive disorder within the past year requiring treatment
17. History of or current panic disorder, psychosis, bipolar disorder, or eating
disorders
18. Alcohol or drug abuse/dependency within the past year
19. Use of another investigational drug within 30 days
20. Intention to donate blood or blood products during the treatment phase of the study
21. Use of tobacco products other than cigarettes or use of marijuana
22. Use of nicotine replacement therapy, clonidine, varenicline, bupropion, or
nortriptyline within the month prior to enrollment or intention to use medication
that might interfere with study medication
23. Body Mass Index (calculated as weight in kilograms divided by the square of height in
meters) less than 15 or greater than 38 or weight less than 45 kg.
24. Females of childbearing potential who are pregnant, nursing, or not practicing
effective contraception (oral injectable, or implantable contraceptives, intrauterine
device, or barrier method with spermacide)
Locations and Contacts
Yale University School of Medicine Substance Abuse Treatment Unit, New Haven, Connecticut 06511, United States
Additional Information
Starting date: July 2007
Last updated: August 30, 2010
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