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

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00129246
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
• Enrollment: 40
• Location: 1
• Arms: 2
• Duration (Months): 12
• Patients Per Site Per Month: 3.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Smoking; Nicotine Dependence	Drug: Naltrexone; Drug: Bupropion	Phase 1/Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Naltrexone & Bupropion to Stop Smoking With Less Weight Gain
• Study Start Date: Dec 1, 2004
• Actual Study Completion Date: Dec 1, 2005

Arms and Interventions

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: 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.; 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.

Outcome Measures

Primary Outcome Measures

1. Smoking Cessation [Week 6]

   Smoking cessation is defined as the number of patients that displayed continuous 6-week abstinence from the quit date.

2. Point Prevalence Abstinence [Week 6]

   Point prevalence abstinence is defined as the number of patients reporting point prevalence abstinence over the last 7 days.

3. Weight Gain [Week 6]

   Weight gain for for the entire sample in pounds at 6 weeks.

Secondary Outcome Measures

1. Weight Gain Abstinent Participants [Week 6]

   Weight gain (in pounds) for the patients that were continuously abstinent at 6 weeks.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale University School of Medicine Substance Abuse Treatment Unit	New Haven	Connecticut	United States	06511

Sponsors and Collaborators

• Yale University
• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: Benjamin Toll, Ph.D., Yale University School of Medicine Department of Psychiatry

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT00129246
• Other Study ID Numbers: NIAAAOMA15632-B; P50AA015632; NIH Grant 9 P50-AA15632
• First Posted: Aug 11, 2005
• Last Update Posted: Dec 3, 2020
• Last Verified: Nov 1, 2020

• Keywords provided by Yale University: Tobacco; Smoking; Weight; Weight perception; Naltrexone; Bupropion
• Additional relevant MeSH terms: Weight Gain; Tobacco Use Disorder; Naltrexone; Bupropion

Study Results

Participant Flow

Arm/Group Title	Bupropion Only	Naltrexone +Bupropion
Arm/Group Description	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). 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.	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). 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. 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.
Period Title: Overall Study
STARTED	20	20
COMPLETED	20	20
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Bupropion Only	Naltrexone +Bupropion	Total
Arm/Group Description	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). 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.	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). 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. 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.	Total of all reporting groups
Overall Participants	20	20	40
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.3 (12.3)	43.0 (11.2)	42.7 (11.6)
Sex: Female, Male (Count of Participants)
Female	14 70%	14 70%	28 70%
Male	6 30%	6 30%	12 30%

Outcome Measures

1. Primary Outcome

Title	Smoking Cessation
Description	Smoking cessation is defined as the number of patients that displayed continuous 6-week abstinence from the quit date.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

Per protocol analysis

Arm/Group Title	Bupropion Only	Naltrexone +Bupropion
Arm/Group Description	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). 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.	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). 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. 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.
Measure Participants	20	20
Number [participants]	6 30%	6 30%

2. Primary Outcome

Title	Point Prevalence Abstinence
Description	Point prevalence abstinence is defined as the number of patients reporting point prevalence abstinence over the last 7 days.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

Per protocol analysis

Arm/Group Title	Bupropion Only	Naltrexone +Bupropion
Arm/Group Description	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). 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.	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). 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. 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.
Measure Participants	20	20
Number [participants]	8 40%	8 40%

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Per protocol analysis

Arm/Group Title	Bupropion Only	Naltrexone +Bupropion
Arm/Group Description	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). 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.	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). 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. 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.
Measure Participants	6	6
Mean (Standard Deviation) [lbs]	3.17 (2.04)	1.67 (3.17)

4. Primary Outcome

Title	Weight Gain
Description	Weight gain for for the entire sample in pounds at 6 weeks.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

Per protocol analysis

Arm/Group Title	Bupropion Only	Naltrexone +Bupropion
Arm/Group Description	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). 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.	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). 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. 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.
Measure Participants	20	20
Mean (Standard Deviation) [lbs]	1.25 (2.90)	0.28 (3.88)

Adverse Events

Arm/Group Title	Bupropion Only		Naltrexone +Bupropion
Arm/Group Description	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). 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.		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). 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. 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.
All Cause Mortality
	Bupropion Only		Naltrexone +Bupropion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Bupropion Only		Naltrexone +Bupropion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Bupropion Only		Naltrexone +Bupropion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/20 (40%)		9/20 (45%)
Ear and labyrinth disorders
Ringing in ears	0/20 (0%)	0	1/20 (5%)	1
Gastrointestinal disorders
Nausea	1/20 (5%)	1	5/20 (25%)	5
Vomiting	1/20 (5%)	1	1/20 (5%)	1
Diarrhea	1/20 (5%)	1	0/20 (0%)	0
Constipation	0/20 (0%)	0	2/20 (10%)	2
General disorders
Fatigue	0/20 (0%)	0	1/20 (5%)	1
Dry mouth	4/20 (20%)	4	4/20 (20%)	4
Nervous system disorders
Headache	0/20 (0%)	0	2/20 (10%)	2
Dizziness	0/20 (0%)	0	1/20 (5%)	1
Psychiatric disorders
Nervousness/anxiety	2/20 (10%)	2	4/20 (20%)	4
Insomnia	5/20 (25%)	5	3/20 (15%)	3
Irritability	2/20 (10%)	2	2/20 (10%)	2
Skin and subcutaneous tissue disorders
Pruritus	2/20 (10%)	2	0/20 (0%)	0
Alopecia	0/20 (0%)	0	1/20 (5%)	1
Sweating	1/20 (5%)	1	2/20 (10%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.