Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking

• Sponsor: Lisa Sanderson Cox, PhD (Other)
• Overall Status: Completed
• CT.gov ID: NCT00666978
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 540
• Locations: 2
• Arms: 2
• Duration (Months): 30
• Patients Per Site: 270
• Patients Per Site Per Month: 9

Study Details

Study Description

Brief Summary

RATIONALE: A stop-smoking plan that includes health education counseling and bupropion may help African-American smokers stop smoking. It is not yet known whether health education counseling is more effective with or without bupropion in helping African Americans stop smoking.

PURPOSE: This clinical trial is studying health education counseling and bupropion to see how well they work compared with a placebo and health education counseling in helping African Americans smokers stop smoking.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer; Cervical Cancer; Esophageal Cancer; Gastric Cancer; Head and Neck Cancer; Kidney Cancer; Leukemia; Liver Cancer; Lung Cancer; Pancreatic Cancer; Tobacco Use Disorder	Behavioral: smoking cessation intervention; Drug: bupropion hydrochloride; Genetic: gene expression analysis; Genetic: polymerase chain reaction; Other: counseling intervention; Other: educational intervention; Procedure: psychosocial assessment and care	Phase 4

Detailed Description

OBJECTIVES:

Primary

• To evaluate the efficacy of bupropion hydrochloride and health education counseling vs placebo and health education counseling for smoking cessation among African Americans who are light smokers.

Secondary

• To characterize CYP2A6 activity in African Americans who are light smokers by evaluating phenotype (3'hydroxycotinine/cotinine ratio [3HC/COT]) and CYP2A6 genotype.

• To evaluate the relationship between CYP2A6 activity and smoking cessation outcomes.

• To evaluate CYP2A6 genetic polymorphisms associated with nicotine and cotinine metabolism in African Americans who are light smokers.

• To measure baseline cotinine and metabolite levels to evaluate the nicotine metabolism phenotype of 3HC/COT.

• To evaluate the relationship between nicotine metabolism phenotype of 3HC/COT and smoking cessation outcomes.

• To evaluate CYP2A6 genotype as a predictor of smoking cessation outcomes.

Tertiary

• To characterize CYP2B6 activity in African Americans who are light smokers by evaluating phenotype and CYP2B6 genotype.

• To evaluate the relationship between CYP2B6 activity and smoking cessation outcomes.

• To measure steady state bupropion hydrochloride and metabolite levels to identify a bupropion metabolism phenotype.

• To evaluate the relationship between bupropion hydrochloride metabolism phenotype and smoking cessation outcomes.

• To evaluate the relationship between CYP2B6 genetic polymorphisms (genotype) and blood levels of bupropion hydrochloride and active metabolites (phenotype).

• To determine the effects of CYP2B6 genotype as predictors of smoking cessation outcomes.

OUTLINE: Participants are randomized to one of two arms.

• Arm I: Participants receive oral bupropion hydrochloride once or twice daily in weeks 0-6. Participants also undergo 6 sessions of health education counseling conducted in person during clinic visits in weeks 0, 3, and 7 and via telephone in weeks 1, 5, and

1. The health education counseling sessions include providing information about the risks of continued smoking and the benefits of quitting, developing a quit plan, outlining a concrete quit day preparation plan, discussing strategies for successful quitting, building social support, reducing stress, recognizing and managing withdrawal and craving, overcoming barriers to abstinence, and using medication for smoking cessation. Participants receive Kick It at Swope: Stop Smoking Guide, a culturally-sensitive smoking cessation guide, to review with their study counselor during the first counseling session.

• Arm II: Participants receive an oral placebo once or twice daily in weeks 0-6. Participants also undergo health education counseling as in arm I.

Participants complete baseline questionnaires about demographics, smoking history, and psychometrics, including the following: racial identity, depressive symptoms, alcohol use, stress, smoking consequences, social support, environmental influences of smoking, adherence to study medication, nicotine withdrawal, craving, and mood.

Participants undergo serum sample collection in weeks 0 and 3. To standardize the time since the last cigarette, participants are asked to smoke one cigarette prior to serum sample collection in week 0. Samples are analyzed for nicotine metabolism phenotype and bupropion hydrochloride metabolism phenotype by liquid chromatography and mass spectrometry and CYP2A6 and CYP2B6 genotype by polymerase chain reaction and polymorphism analysis. Participants who self-report abstinence also undergo saliva sample collection in weeks 7 and 26 to measure cotinine levels to verify smoking status.

After completion of study intervention, participants are followed at 6 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 540 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Enhancing Tobacco Use Treatment for African American Light Smokers
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bupropion Arm Subjects undergo smoking cessation intervention and take bupropion.	Behavioral: smoking cessation intervention; Drug: bupropion hydrochloride; Genetic: gene expression analysis; Genetic: polymerase chain reaction; Other: counseling intervention; Other: educational intervention; Procedure: psychosocial assessment and care
Placebo Comparator: Health Education Arm Subjects receive counseling intervention and take placebo.	Behavioral: smoking cessation intervention; Genetic: gene expression analysis; Genetic: polymerase chain reaction; Other: counseling intervention; Other: educational intervention; Procedure: psychosocial assessment and care

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Salivary Cotinine-verified Smoking Abstinence at 6 Months [6 months]

   Salivary cotinine-verified smoking abstinence at 6 months. A cut point of 15 ng/ml was used to differentiate smokers from nonsmokers.

Secondary Outcome Measures

1. Number of Slow and Fast Metabolizers by Metabolite Ratio [Weeks 0]

   Analyzed CYP2A6 by activity, called the nicotine metabolite ratio using a split between slow and fast metabolism at 0.31. The variants present in people in the slow genotype group include *17, *20, *23,*27, *35, *9, *2, *25, *26, and *4. The fast metabolizers have none of the variant alleles tested. Blood samples were collected for 3HC/COT ratio at Week 0.

2. Number of Participants for Each CYP2B6 Allele [Week 3]

   We genotyped CYP2B6 in 268 from the Bupropion arm as this polymorphism is related to bupropion metabolism.

3. Number of Slow and Fast Metabolizers by Genotype [Week 0]

   Analyzed CYP2A6 by genotype. The variants present in people in the slow genotype group include *17, *20, *23,*27, *35, *9, *2, *25, *26, and *4. The fast metabolizers have none of the variant alleles tested. Slow metabolizers have any reduction or loss of function variant. Fast metabolizers are *1/*1 genotype by exclusion.

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• African American who has smoked ≤ 10 cigarettes per day for ≥ 2 years AND has smoked for ≥ 25 days within the past month

• Not a heavy smoker

• No other forms of tobacco within the past 30 days

• Must be interested in stopping smoking

• No other smoker in the household enrolled in this study

PATIENT CHARACTERISTICS:

• Has a home address and a functioning telephone number

• Not planning to move from the Kansas City metro area within the next 12 months

• Not pregnant or nursing

• Negative pregnancy test

• No alcohol or substance abuse within the past year

• Not currently drinking ≥ 14 alcoholic drinks per week

• No binge drinking (5 or more drinks on one occasion) on at least two occasions within the past month

• No history of seizures or head trauma

• No history of bulimia or anorexia nervosa

• No myocardial infarction within the past 30 days

• No reported use of opiates, cocaine, or stimulants

• No diabetes requiring oral hypoglycemics or insulin

PRIOR CONCURRENT THERAPY:

• More than 30 days since prior nicotine replacement therapy, fluoxetine, clonidine, buspirone, or doxepin

• No other concurrent medication that contains bupropion hydrochloride

• No concurrent psychoactive medications

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
2	Swope Health Central	Kansas City	Missouri	United States	64130

Sponsors and Collaborators

• Lisa Sanderson Cox, PhD
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Lisa S. Cox, PhD, University of Kansas

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Lisa Sanderson Cox, PhD, Research Assistant Professor, University of Kansas Medical Center
• ClinicalTrials.gov Identifier: NCT00666978
• Other Study ID Numbers: 10332; R01CA091912; KUMC-HSC-10332; KUMC-070313
• First Posted: Apr 25, 2008
• Last Update Posted: Nov 13, 2017
• Last Verified: Oct 1, 2017

• Keywords provided by Lisa Sanderson Cox, PhD, Research Assistant Professor, University of Kansas Medical Center: bladder cancer; cervical cancer; esophageal cancer; gastric cancer; renal cell carcinoma; adult primary liver cancer; non-small cell lung cancer; small cell lung cancer; pancreatic cancer; hypopharyngeal cancer; laryngeal cancer; lip and oral cavity cancer; nasopharyngeal cancer; oropharyngeal cancer; paranasal sinus and nasal cavity cancer; adult acute myeloid leukemia; tobacco use disorder
• Additional relevant MeSH terms: Lung Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms; Uterine Cervical Neoplasms; Urinary Bladder Neoplasms; Esophageal Neoplasms; Liver Neoplasms; Tobacco Use Disorder; Bupropion

Study Results

Participant Flow

Arm/Group Title	Bupropion Arm	Placebo Arm
Arm/Group Description	270 African American adults received bupropion (150mg bid) for 7 weeks in addition to health education counseling.	270 African American adults received placebo for 7 weeks in addition to health education counseling.
Period Title: Overall Study
STARTED	270	270
COMPLETED	192	187
NOT COMPLETED	78	83

Baseline Characteristics

Arm/Group Title	Bupropion Arm	Placebo Arm	Total
Arm/Group Description	270 African American adults received bupropion (150mg bid) for 7 weeks in addition to health education counseling.	270 African American adults received placebo for 7 weeks in addition to health education counseling.	Total of all reporting groups
Overall Participants	270	270	540
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.8 (11.1)	46.2 (11.5)	46.5 (11.3)
Sex: Female, Male (Count of Participants)
Female	174 64.4%	183 67.8%	357 66.1%
Male	96 35.6%	87 32.2%	183 33.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	270 100%	270 100%	540 100%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	270 100%	270 100%	540 100%
Married or living with partner (Count of Participants)
Count of Participants [Participants]	91 33.7%	75 27.8%	166 30.7%
Monthly family income <$1800 (Count of Participants)
Count of Participants [Participants]	169 62.6%	158 58.5%	327 60.6%
Education > or = high school (Count of Participants)
Count of Participants [Participants]	225 83.3%	229 84.8%	454 84.1%
Weight (lbs) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [lbs]	196.1 (51.8)	194.8 (54.0)	195.5 (52.9)
BMI (kg/m 2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m 2]	31.1 (7.6)	31.1 (8.1)	31.1 (7.9)
Depression(CESD-10) score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	7.2 (4.9)	8.2 (5.5)	7.7 (5.2)
Stress (PSS-4) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	4.9 (3.1)	5.5 (3.3)	5.2 (3.2)
Serum Cotinine (ng/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/ml]	268.7 (160.2)	283.0 (151.2)	275.8 (155.8)
Exhaled Carbon monoxide (ppm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ppm]	15.8 (9.4)	17.1 (10.5)	16.4 (10.0)
Cigarettes per day (cigarettes per day) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cigarettes per day]	8.0 (2.6)	7.9 (2.4)	8.0 (2.5)
Fagerstrom Test for Nicotine Dependence- 6 item (score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score]	3.1 (1.7)	3.3 (1.7)	3.2 (1.7)
Time to first cigarette,< or = 30 minutes (Count of Participants)
Count of Participants [Participants]	191 70.7%	199 73.7%	390 72.2%
Smoke Menthol Cigarettes (Count of Participants)
Count of Participants [Participants]	224 83%	228 84.4%	452 83.7%
Quit Attempts (Quit Attempts) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Quit Attempts]	3.5 (7.9)	3.9 (7.4)	3.7 (7.7)
Pharmacotherapy use during most recent quit attempt (Count of Participants)
Count of Participants [Participants]	72 26.7%	61 22.6%	133 24.6%
Age of first cigarette (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	17.5 (5.8)	18.1 (7.3)	17.6 (5.9)
Age started smoking regularly (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	21.1 (6.7)	21.3 (7.4)	21.1 (7.1)
Motivation Scale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	9.7 (0.8)	9.8 (0.7)	9.7 (0.8)
Confidence Scale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	7.9 (2.1)	7.8 (2.0)	7.9 (2.4)
Smoke-free household (Count of Participants)
Count of Participants [Participants]	65 24.1%	67 24.8%	132 24.4%
California Tobacco Survey: Inhale deeply (Count of Participants)
Count of Participants [Participants]	65 24.1%	61 22.6%	126 23.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Salivary Cotinine-verified Smoking Abstinence at 6 Months
Description	Salivary cotinine-verified smoking abstinence at 6 months. A cut point of 15 ng/ml was used to differentiate smokers from nonsmokers.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bupropion Arm	Placebo Arm
Arm/Group Description	270 African American adults received bupropion (150mg bid) for 7 weeks in addition to health education counseling.	270 African American adults received placebo for 7 weeks in addition to health education counseling.
Measure Participants	270	270
Count of Participants [Participants]	36 13.3%	27 10%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bupropion Arm, Placebo Arm
	Comments	Based on our previous studies, sample size was determined a priori assuming a two-sided x2 test with a type I error rate of .05, a power of 80%, and a cotinine-verified abstinence rate of 15% in the placebo group and 25% in the bupropion SR group at week 26, with the assumption that those lost to follow-up would be imputed as smokers.
	Type of Statistical Test	Superiority
	Comments	The x2 test was used to determine whether there was a difference between treatment groups (bupropion SR vs placebo) in verified 7-day point prevalence abstinence at week 26, imputing the missing participants as smokers.
Statistical Test of Hypothesis	p-Value	.23
	Comments	All tests of statistical significance were two-sided, and all P values less than .05 were considered statistically significant.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.39
	Confidence Interval	(2-Sided) 95%; 0.82 to 2.35
	Parameter Dispersion	Type: Value:
	Estimation Comments	Raw proportions were used to estimate the verified cessation rate in each group and corresponding odds ratio along with its 95% confidence interval .

2. Secondary Outcome

Title	Number of Slow and Fast Metabolizers by Metabolite Ratio
Description	Analyzed CYP2A6 by activity, called the nicotine metabolite ratio using a split between slow and fast metabolism at 0.31. The variants present in people in the slow genotype group include *17, *20, *23,*27, *35, *9, *2, *25, *26, and *4. The fast metabolizers have none of the variant alleles tested. Blood samples were collected for 3HC/COT ratio at Week 0.
Time Frame	Weeks 0

Outcome Measure Data

Analysis Population Description

This variant is related to nicotine metabolism and was collected from all study participants but not analyzed by study arm as it does not relate to the study medication. Data pre-specified to be collected and reported as a single arm.

Arm/Group Title	All Study Participants
Arm/Group Description	All study participants were African American adults and received either bupropion (150mg bid) for 7 weeks in addition to health education counseling or placebo for 7 weeks in addition to health education counseling.
Measure Participants	450
Fast Metabolizers by Nicotine Metabolite Ratio	236 87.4%
Slow Metabolizers by Nicotine Metabolite Ratio	214 79.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bupropion Arm
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0022
	Comments	This reflects Week 7.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.95 to 0.99
	Parameter Dispersion	Type: Value:
	Estimation Comments	This reflects Week 7.

3. Secondary Outcome

Title	Number of Participants for Each CYP2B6 Allele
Description	We genotyped CYP2B6 in 268 from the Bupropion arm as this polymorphism is related to bupropion metabolism.
Time Frame	Week 3

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bupropion Arm
Arm/Group Description	270 African American adults received bupropion (150mg bid)for 7 weeks in addition to health education counseling.
Measure Participants	268
CYP2B6*4 Allele Frequency	2 0.7%
CYP2B6*5 Allele Frequency	6 2.2%
CYP2B6*6 Allele Frequency	95 35.2%
CYP2B6*9 Allele Frequency	0 0%
CYP2B6*16 Allele Frequency	0 0%
CYP2B6*18 Allele Frequency	17 6.3%
CYP2B6*22 Allele Frequency	6 2.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bupropion Arm
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments	Analysis relied on examining quit rates using linear regression, where the hydroxybupropion was a significant predictor of smoking cessation. CYP2B6 genotype was not a direct significant predictor of cessation in either the placebo or bupropion arm.
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.82
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bupropion adherent individuals with higher hydroxybupropion levels were more likely to be abstinent at Weeks 3, 7 and 26 compared to individuals with lower hydroxybupropion levels.

4. Secondary Outcome

Title	Number of Slow and Fast Metabolizers by Genotype
Description	Analyzed CYP2A6 by genotype. The variants present in people in the slow genotype group include *17, *20, *23,*27, *35, *9, *2, *25, *26, and *4. The fast metabolizers have none of the variant alleles tested. Slow metabolizers have any reduction or loss of function variant. Fast metabolizers are *1/*1 genotype by exclusion.
Time Frame	Week 0

Outcome Measure Data

Analysis Population Description

This variant is related to nicotine metabolism and was collected from all study participants but not analyzed by study arm as it does not relate to the study medication. Data pre-specified to be collected and reported as a single arm. Blood was unable to be analyzed for CYP2A6 genotype for 6 participants.

Arm/Group Title	All Study Participants
Arm/Group Description	All study participants were African American adults and received either bupropion (150mg bid) for 7 weeks in addition to health education counseling or placebo for 7 weeks in addition to health education counseling.
Measure Participants	534
Slow Metabolizers by Genotype	265 98.1%
Fast Metabolizers by Genotype	269 99.6%

Adverse Events

Time Frame	16 weeks
Arm/Group Title	Bupropion Arm		Placebo Arm
Arm/Group Description	270 African American adults received bupropion (150mg bid) for 7 weeks in addition to health education counseling.		270 African American adults received placebo for 7 weeks in addition to health education counseling.
All Cause Mortality
	Bupropion Arm		Placebo Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/270 (0%)		0/270 (0%)
Serious Adverse Events
	Bupropion Arm		Placebo Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/270 (3%)		13/270 (4.8%)
Cardiac disorders
Atrioventricular block	1/270 (0.4%)	1	0/270 (0%)	0
Chest Pain	1/270 (0.4%)	1	0/270 (0%)	0
Coagulation	0/270 (0%)	0	1/270 (0.4%)	1
Gastrointestinal disorders
Toothache	0/270 (0%)	0	1/270 (0.4%)	1
Infections and infestations
Lung infection	0/270 (0%)	0	2/270 (0.7%)	2
MIddle ear infection	0/270 (0%)	0	1/270 (0.4%)	1
Musculoskeletal and connective tissue disorders
Muscle Weakness	1/270 (0.4%)	1	0/270 (0%)	0
Upper extremity dysfunction	1/270 (0.4%)	1	0/270 (0%)	0
Arthritis	0/270 (0%)	0	1/270 (0.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Treatment related secondary malignancy	0/270 (0%)	0	2/270 (0.7%)	2
Tumor pain	0/270 (0%)	0	1/270 (0.4%)	1
Nervous system disorders
Syncope	1/270 (0.4%)	1	0/270 (0%)	0
Acoustic nerve disorder	0/270 (0%)	0	1/270 (0.4%)	1
Psychiatric disorders
Insomnia	1/270 (0.4%)	1	1/270 (0.4%)	1
Depression	0/270 (0%)	0	2/270 (0.7%)	2
Personality Change	1/270 (0.4%)	1	0/270 (0%)	0
Skin and subcutaneous tissue disorders
Infection, Skin	1/270 (0.4%)	1	0/270 (0%)	0
Other (Not Including Serious) Adverse Events
	Bupropion Arm		Placebo Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	46/270 (17%)		29/270 (10.7%)
Gastrointestinal disorders
Nausea	11/270 (4.1%)	11	5/270 (1.9%)	5
Nervous system disorders
Headache	9/270 (3.3%)	9	15/270 (5.6%)	15
Psychiatric disorders
Insomnia	26/270 (9.6%)	26	9/270 (3.3%)	9

Limitations/Caveats

Over half of the participants who expressed interest in this study were ineligible according to study protocol. The lack of assessment between standardized assessment points limited the ability to characterize the process of relapse.

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.