Naltrexone and Varenicline: Weight Gain and Tolerability in Cigarette Smokers

This study has been completed.
Sponsor:
Collaborators:
Information provided by:
Yale University
ClinicalTrials.gov Identifier:
NCT00502216
First received: July 13, 2007
Last updated: August 30, 2010
Last verified: August 2010
  Purpose

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.


Condition Intervention Phase
Smoking
Nicotine Dependence
Drug: Naltrexone
Drug: Varenicline
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Naltrexone and Varenicline: Weight Gain and Tolerability in Smokers

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Weight Gain in Treatment Completers [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Weight Gain in Participants Who Are Continuously Abstinent for the Last 4 Weeks of Treatment [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Tolerability of the Combination of 25 mg Naltrexone and 2 mg Varenicline [ Time Frame: 11 weeks ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: July 2007
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Arm 1 (Experimental) = Varenicline (Chantix) 1 mg oral tablet twice per day + naltrexone 25 mg oral capsule once per day
Drug: Naltrexone
Varenicline (Chantix) 1 mg oral tablet twice per day + naltrexone 25 mg oral capsule once per day
Drug: Varenicline
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 Name: Chantix
Placebo Comparator: 2
Arm 2 (Placebo Comparator) = Varenicline (Chantix) 1 mg oral tablet twice per day + placebo naltrexone 25 mg oral capsule once per day
Drug: Varenicline
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 Name: Chantix

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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00502216

Locations
United States, Connecticut
Yale University School of Medicine Substance Abuse Treatment Unit
New Haven, Connecticut, United States, 06511
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Benjamin A. Toll, PhD Yale University
  More Information

No publications provided

Responsible Party: Benjamin Toll, Ph.D., Assistant Professor, Yale University
ClinicalTrials.gov Identifier: NCT00502216     History of Changes
Other Study ID Numbers: NIAAA_TOL-AA15632, P50AA015632, NIH Grant P50-AA15632, NIH Grant K12-DA00167
Study First Received: July 13, 2007
Results First Received: June 3, 2010
Last Updated: August 30, 2010
Health Authority: United States: Federal Government

Keywords provided by Yale University:
Tobacco
Smoking
Weight
Naltrexone
Varenicline

Additional relevant MeSH terms:
Tobacco Use Disorder
Smoking
Weight Gain
Substance-Related Disorders
Mental Disorders
Habits
Body Weight Changes
Body Weight
Signs and Symptoms
Naltrexone
Varenicline
Narcotic Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014