Naltrexone and Varenicline: Weight Gain and Tolerability in Cigarette Smokers

NCT ID: NCT00502216

Last Updated: 2018-01-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2009-06-30

Brief 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.

Conditions

Smoking; Nicotine Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

1

Arm 1 (Experimental) = Varenicline (Chantix) 1 mg oral tablet twice per day + naltrexone 25 mg oral capsule once per day

Group Type: EXPERIMENTAL

Naltrexone

Intervention Type: DRUG

Varenicline (Chantix) 1 mg oral tablet twice per day + naltrexone 25 mg oral capsule once per day

Varenicline

Intervention Type: DRUG

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

2

Arm 2 (Placebo Comparator) = Varenicline (Chantix) 1 mg oral tablet twice per day + placebo naltrexone 25 mg oral capsule once per day

Group Type: PLACEBO_COMPARATOR

Varenicline

Intervention Type: DRUG

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

Interventions

Naltrexone

Varenicline (Chantix) 1 mg oral tablet twice per day + naltrexone 25 mg oral capsule once per day

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Chantix

Eligibility 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Benjamin A. Toll, PhD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale University School of Medicine Substance Abuse Treatment Unit

New Haven, Connecticut, United States

Countries

United States

References

Livingstone-Banks J, Fanshawe TR, Thomas KH, Theodoulou A, Hajizadeh A, Hartman L, Lindson N. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2023 May 5;5(5):CD006103. doi: 10.1002/14651858.CD006103.pub8.

Reference Type: DERIVED

PMID: 37142273 (View on PubMed)

Other Identifiers

P50AA015632

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NIH Grant P50-AA15632

Identifier Type: -

Identifier Source: secondary_id

NIH Grant K12-DA00167

Identifier Type: -

Identifier Source: secondary_id

0704002538

Identifier Type: -

Identifier Source: org_study_id