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Naltrexone and Varenicline: Weight Gain and Tolerability in Cigarette Smokers

Primary Purpose

Smoking, Nicotine Dependence

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Naltrexone

Varenicline

About this trial

This is an interventional treatment trial for Smoking focused on measuring Tobacco, Smoking, Weight, Naltrexone, Varenicline

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Between the ages of 18 and 75
Smoking 10 or more cigarettes per day
Fewer than 3 months of smoking abstinence in the past year
Motivated to stop smoking

Exclusion Criteria:

Current use of opiates, and/or a urine toxicology screen positive for opiates
Chronic pain conditions necessitating opioid treatment (naltrexone, an opioid antagonist will make these medications ineffective)
Evidence of significant hepatocellular injury as evidence by AST or ALT >3 x normal or elevated bilirubin
History of cirrhosis
Any serious or unstable disease within 6 months
Seizure risk
Diabetes mellitus requiring insulin or oral hypoglycemic medications
Hepatic or renal impairment
Use of a monoamine oxidase inhibitor in the prior 14 days
Clinically significant cardiovascular disease within 6 months
Uncontrolled hypertension
Baseline systolic blood pressure higher than 150 mm Hg or diastolic blood pressure higher than 95 mm Hg
Severe chronic obstructive pulmonary disease
History of cancer (except treated basal cell or squamous cell carcinoma of the skin)
History of clinically significant allergic reactions
Major depressive disorder within the past year requiring treatment
History of or current panic disorder, psychosis, bipolar disorder, or eating disorders
Alcohol or drug abuse/dependency within the past year
Use of another investigational drug within 30 days
Intention to donate blood or blood products during the treatment phase of the study
Use of tobacco products other than cigarettes or use of marijuana
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
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.
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)

Sites / Locations

Yale University School of Medicine Substance Abuse Treatment Unit

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm Description

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

Outcomes

Primary Outcome Measures

Weight Gain in Treatment Completers

Secondary Outcome Measures

Weight Gain in Participants Who Are Continuously Abstinent for the Last 4 Weeks of Treatment

Tolerability of the Combination of 25 mg Naltrexone and 2 mg Varenicline

Tolerability was measured by tracking adverse events. These data are reported in detail in the adverse events section. Presented are an unduplicated count of participants that experienced at least 1 adverse event.

Full Information

NCT ID

NCT00502216

First Posted

July 13, 2007

Last Updated

January 12, 2018

Sponsor

Yale University

Collaborators

National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Drug Abuse (NIDA)

1. Study Identification

Unique Protocol Identification Number

NCT00502216

Brief Title

Naltrexone and Varenicline: Weight Gain and Tolerability in Cigarette Smokers

Official Title

Naltrexone and Varenicline: Weight Gain and Tolerability in Smokers

Study Type

Interventional

2. Study Status

Record Verification Date

January 2018

Overall Recruitment Status

Completed

Study Start Date

July 2007 (undefined)

Primary Completion Date

June 2009 (Actual)

Study Completion Date

June 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Yale University

Collaborators

National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Drug Abuse (NIDA)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Smoking, Nicotine Dependence

Keywords

Tobacco, Smoking, Weight, Naltrexone, Varenicline

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

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

Arm Title

Arm Type

Placebo Comparator

Arm Description

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

Intervention Name(s)

Naltrexone

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Varenicline

Other Intervention Name(s)

Chantix

Intervention Description

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

Primary Outcome Measure Information:

Title

Weight Gain in Treatment Completers

Time Frame

baseline and 12 weeks

Secondary Outcome Measure Information:

Title

Weight Gain in Participants Who Are Continuously Abstinent for the Last 4 Weeks of Treatment

Time Frame

4 weeks

Title

Tolerability of the Combination of 25 mg Naltrexone and 2 mg Varenicline

Description

Time Frame

11 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Between the ages of 18 and 75 Smoking 10 or more cigarettes per day Fewer than 3 months of smoking abstinence in the past year Motivated to stop smoking Exclusion Criteria: Current use of opiates, and/or a urine toxicology screen positive for opiates Chronic pain conditions necessitating opioid treatment (naltrexone, an opioid antagonist will make these medications ineffective) Evidence of significant hepatocellular injury as evidence by AST or ALT >3 x normal or elevated bilirubin History of cirrhosis Any serious or unstable disease within 6 months Seizure risk Diabetes mellitus requiring insulin or oral hypoglycemic medications Hepatic or renal impairment Use of a monoamine oxidase inhibitor in the prior 14 days Clinically significant cardiovascular disease within 6 months Uncontrolled hypertension Baseline systolic blood pressure higher than 150 mm Hg or diastolic blood pressure higher than 95 mm Hg Severe chronic obstructive pulmonary disease History of cancer (except treated basal cell or squamous cell carcinoma of the skin) History of clinically significant allergic reactions Major depressive disorder within the past year requiring treatment History of or current panic disorder, psychosis, bipolar disorder, or eating disorders Alcohol or drug abuse/dependency within the past year Use of another investigational drug within 30 days Intention to donate blood or blood products during the treatment phase of the study Use of tobacco products other than cigarettes or use of marijuana 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 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. 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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Benjamin A. Toll, PhD

Organizational Affiliation

Yale University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Yale University School of Medicine Substance Abuse Treatment Unit

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06511

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Naltrexone and Varenicline: Weight Gain and Tolerability in Cigarette Smokers

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