Low-Dose Naltrexone Combined With Bupropion to Stop Smoking With Less Weight Gain

Naltrexone & Bupropion to Stop Smoking With Less Weight Gain

This study will test a combination of the drugs naltrexone and bupropion with weight-concerned smokers to investigate whether or not this combination of drugs improves smoking cessation quit rates and minimizes post quit weight gain.

Study Overview

• Status: Completed
• Conditions: Smoking; Nicotine Dependence
• Intervention / Treatment: Drug: Bupropion; Drug: Naltrexone

Detailed Description

This is an open label smoking cessation clinical trial of 25 mg naltrexone with 300 mg bupropion sustained-release (SR) in six male and fourteen female participants. This pilot study is being conducted to determine:

• effect size estimates for smoking cessation and post-cessation weight gain, which will be used to compute the sample size needed for a large-scale clinical trial; and
• compliance with a combination of 25 mg naltrexone and 300 mg bupropion SR. In addition to examining the sample in this study, the investigators plan to compare this sample to a sample of matched controls.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University School of Medicine Substance Abuse Treatment Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ages 18 and older
• Willingness and ability to give written consent
• Smoking at least 10 cigarettes per day for at least 1 year
• Baseline expired carbon-monoxide level of at least 10 ppm
• Weigh at least 100 lbs.
• English-speaking
• One person per household
• At least 1 prior quit attempt
• Concern about gaining weight. This will be assessed using a questionnaire that will provide a rating system to determine qualified participants.

Exclusion Criteria:

• Pregnant or nursing women or women attempting to conceive
• Serious current neurologic, psychiatric or medical illness, including unstable cardiac, hepatic, or renal disease and diabetes and hypertension
• Current alcohol dependence
• 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 evidenced by AST or ALT >3 x normal or elevated bilirubin
• History of cirrhosis
• Body mass index (BMI) greater than 35
• History of anorexia nervosa or bulimia
• Current major depression
• Currently taking Toprol-XL (or metoprolol succinate)
• History of seizure disorder or serious brain injury
• Current use of smokeless tobacco, pipes, cigars, nicotine gum, nicotine patch, nicotine inhaler, nicotine lozenge, nicotine nasal spray, or bupropion
• Previous hypersensitivity to bupropion
• Patients requiring concomitant therapy with any psychotropic drug
• Participation in the Framing Messages for Smoking Cessation With Bupropion study (HIC#: 10880)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Bupropion only; The placebo comparator was a group of matched controls who received an identical psychosocial intervention and bupropion SR treatment regimen in a similar 7-week study investigation compared to naltrexone hydrochloride (25 mg/day) in combination with bupropion hydrochloride SR (300 mg/day).	Drug: Bupropion; Starting with the baseline visit, all participants received 150 mg of bupropion SR once per day for 3 days, then twice per day for the duration of the 7-week treatment period.
Experimental: Naltrexone +Bupropion; The active comparator in this 7-week open label study investigation was naltrexone hydrochloride (25 mg/day) in combination with bupropion hydrochloride SR (300 mg/day) compared to matched controls who received an identical psychosocial intervention and bupropion SR treatment regimen (bupropion only).	Drug: Bupropion; Starting with the baseline visit, all participants received 150 mg of bupropion SR once per day for 3 days, then twice per day for the duration of the 7-week treatment period.; Drug: Naltrexone; Participants received naltrexone hydrochloride on the sixth day of bupropion treatment, and the initial dose was 12.5 mg, followed by 25 mg daily for the duration of the 7-week treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Smoking Cessation	Smoking cessation is defined as the number of patients that displayed continuous 6-week abstinence from the quit date.	Week 6
Point Prevalence Abstinence	Point prevalence abstinence is defined as the number of patients reporting point prevalence abstinence over the last 7 days.	Week 6
Weight Gain	Weight gain for for the entire sample in pounds at 6 weeks.	Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight Gain Abstinent Participants	Weight gain (in pounds) for the patients that were continuously abstinent at 6 weeks.	Week 6

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Benjamin Toll, Ph.D., Yale University School of Medicine Department of Psychiatry

Publications and helpful links

General Publications

• Toll BA, Leary V, Wu R, Salovey P, Meandzija B, O'Malley SS. A preliminary investigation of naltrexone augmentation of bupropion to stop smoking with less weight gain. Addict Behav. 2008 Jan;33(1):173-9. doi: 10.1016/j.addbeh.2007.05.012. Epub 2007 Jun 2.

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Study Completion (Actual): December 1, 2005

Study Registration Dates

• First Submitted: August 9, 2005
• First Submitted That Met QC Criteria: August 9, 2005
• First Posted (Estimate): August 11, 2005

Study Record Updates

• Last Update Posted (Actual): December 3, 2020
• Last Update Submitted That Met QC Criteria: November 18, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Smoking; Bupropion; Tobacco; Naltrexone; Weight; Weight perception
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Body Weight; Body Weight Changes; Tobacco Use Disorder; Weight Gain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Sensory System Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Narcotic Antagonists; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Alcohol Deterrents; Dopamine Uptake Inhibitors; Naltrexone; Bupropion
• Other Study ID Numbers: NIAAAOMA15632-B; P50AA015632 (U.S. NIH Grant/Contract); NIH Grant 9 P50-AA15632