Combined Pharmaco/Behavior Therapy in Adolescent Smokers

• Sponsor: Medical University of South Carolina (Other)
• Overall Status: Completed
• CT.gov ID: NCT00330187
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 134
• Location: 1
• Arms: 4
• Actual Duration (Months): 64
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief Summary

In the current proposal, we intend to study the efficacy of bupropion SR with or without combined contingency management (CM) among adolescent cigarette smokers. The proposed study will test not only medication (bupropion SR), but also combination of medication and CM in potentially improving smoking cessation outcomes AND retention of adolescent smokers in the study.

Hypothesis to be tested: Bupropion SR treatment will increase abstinence from cigarette smoking (as measured by urine cotinine and continuous abstinence) in adolescent smokers as compared to treatment with placebo only.

Hypothesis to be tested: Adolescent smokers treated with combined bupropion SR + contingency management (CM) treatment will have increased retention and increased abstinence rates when compared to bupropion SR alone or CM + placebo treated groups (as measured by decreased drop-out of participants, urine cotinine and continuous abstinence).

Hypothesis to be tested: CM will increase the abstinence from cigarette smoking (as measured by urine cotinine and continuous abstinence) in adolescent smokers as compared to treatment with placebo only.

Condition or Disease	Intervention/Treatment	Phase
Nicotine Dependence; Nicotine Use Disorder	Drug: Bupropion SR; Behavioral: Contingency Management; Other: Placebo	Phase 2

Detailed Description

To test the hypotheses, 216 adolescent smokers will be recruited. Fifty-four adolescent smokers will be recruited in each of the four groups: bupropion SR only, bupropion SR + CM, CM + placebo, and placebo only. The cells will be balanced for gender and attention deficit hyperactivity disorder using permuted block randomization. A counseling intervention was added for all groups because it was reasoned that it would be unethical not to provide an active treatment to cigarette smoking adolescents. The counseling intervention will consist of two quit smoking brochures that provide information on tips to help quit smoking.

The study will consist of a one-week lead in period followed by a six-week treatment trial. For the medication groups, medications will be titrated during the one-week lead-in period. The primary outcome measure is urine cotinine and self-report of cigarette use collected using the Time-Line Follow-Back at the end of six weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 134 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Combined Pharmaco/Behavior Therapy in Adolescent Smokers
• Actual Study Start Date: Mar 1, 2004
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bupropion SR + Contingency Management Bupropion SR capsules, with goal dose of 300 mg/day, for 6 weeks of treatment. Contingency Management, with escalating rewards for abstinence (and re-sets for non-abstinence) at twice-weekly visits.	Drug: Bupropion SR; Bupropion SR, with goal dose 300 mg/day, for 6 weeks of active treatment; Behavioral: Contingency Management; Contingency Management provided at twice-weekly visits during the 6-week active treatment. Escalating schedule, with resets, reinforcing smoking abstinence.
Active Comparator: Placebo + Contingency Management Placebo capsules, matched in appearance to Bupropion SR capsules, for 6 weeks of treatment. Contingency Management, with escalating rewards for abstinence (and re-sets for non-abstinence) at twice-weekly visits.	Behavioral: Contingency Management; Contingency Management provided at twice-weekly visits during the 6-week active treatment. Escalating schedule, with resets, reinforcing smoking abstinence.; Other: Placebo; Placebo, matched in appearance to Bupropion SR, for 6 weeks of treatment
Active Comparator: Bupropion SR + No Contingency Management Bupropion SR capsules, with goal dose of 300 mg/day, for 6 weeks of treatment. Contingency Management is not provided in this arm.	Drug: Bupropion SR; Bupropion SR, with goal dose 300 mg/day, for 6 weeks of active treatment
Placebo Comparator: Placebo + No Contingency Management Placebo capsules, matched in appearance to Bupropion SR capsules, for 6 weeks of treatment. Contingency Management is not provided in this arm.	Other: Placebo; Placebo, matched in appearance to Bupropion SR, for 6 weeks of treatment

Outcome Measures

Primary Outcome Measures

1. Biologically-verified 7-day Point Prevalence Smoking Abstinence [End of treatment (week 6)]

   Self-reported abstinence for the past 7 days, confirmed by urine cotinine ≤100 ng/mL

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Regular cigarette smokers smoking at least 5 cigarettes per day as derived by Time-Line Follow-Back method (Sobell et al., 1988). Average number of cigarettes per day (over past 30 days) will be used. Five cigarettes per day may seem low, but based on previous studies, adolescents tend to smoke fewer cigarettes per day as compared to adults.

2. Baseline urine cotinine level greater than 100 ng/ml.

3. Age range of 12 - 21

4. If under 18 yr. of age, parent(s) or guardian(s) able to participate in informed consent and initial assessment, or the participant must provide evidence of emancipated status.

5. For post menarchal female participants: agree to use birth control to avoid pregnancy.

Exclusion Criteria:

1. Active substance abuse/dependence (other than nicotine) within 2 weeks prior to participating in the study

2. Lifetime bipolar affective disorder (BPAD), psychosis, eating disorders. Bupropion may have adverse consequence on participants with these psychiatric diagnoses.

3. Current major depressive disorders. Since bupropion is also an antidepressant, this criteria is to minimize the confound of depressive disorder during the study. History of depressive disorders and current attention deficit hyperactivity disorder (ADHD) will not be an exclusion. We will use permuted block randomization procedure to balance the groups for ADHD.

4. Pregnancy or lactation. The safety of bupropion in pregnancy and during lactation is not well studied.

5. History of seizure disorder or predisposition to seizures (e.g., history of significant head trauma, currently taking medications that lower seizure threshold), since bupropion can lower seizure threshold.

6. History of severe renal, hepatic, neurological, or chronic pulmonary disease. This criterion was chosen due to the hepatic metabolism of bupropion.

7. Unstable medical problems

8. Allergy to bupropion

9. Current treatment with any other medication containing bupropion

10. Current treatment with any monoamine oxidase (MAO) inhibitors currently or within 2 weeks of starting the study since there may be serious and severe medical interactions between MAO inhibitors and bupropion SR.

11. Current treatment with nicotine replacement therapy (NRT)

12. History of intolerance or non-response to bupropion SR.

13. Current (past month) suicide ideation

14. Suicide attempt (past year)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical University of South Carolina	Charleston	South Carolina	United States	29425

Sponsors and Collaborators

• Medical University of South Carolina
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Himanshu P Upadhyaya, MS, MBBS, Medical University of South Carolina

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kevin Gray, MD, Professor, Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT00330187
• Other Study ID Numbers: DA17460; R01DA017460
• First Posted: May 26, 2006
• Last Update Posted: Oct 2, 2018
• Last Verified: Sep 1, 2018

• Keywords provided by Kevin Gray, MD, Professor, Medical University of South Carolina: nicotine dependence; bupropion SR; smoking cessation; adolescents; contingency management
• Additional relevant MeSH terms: Tobacco Use Disorder; Bupropion

Study Results

Participant Flow

Arm/Group Title	Bupropion SR + Contingency Management	Placebo + Contingency Management	Bupropion SR + No Contingency Management	Placebo + No Contingency Management
Arm/Group Description	Bupropion SR capsules, with goal dose of 300 mg/day, for 6 weeks of treatment. Contingency Management, with escalating rewards for abstinence (and re-sets for non-abstinence) at twice-weekly visits. Bupropion SR: Bupropion SR, with goal dose 300 mg/day, for 6 weeks of active treatment Contingency Management: Contingency Management provided at twice-weekly visits during the 6-week active treatment. Escalating schedule, with resets, reinforcing smoking abstinence.	Placebo capsules, matched in appearance to Bupropion SR capsules, for 6 weeks of treatment. Contingency Management, with escalating rewards for abstinence (and re-sets for non-abstinence) at twice-weekly visits. Contingency Management: Contingency Management provided at twice-weekly visits during the 6-week active treatment. Escalating schedule, with resets, reinforcing smoking abstinence. Placebo: Placebo, matched in appearance to Bupropion SR, for 6 weeks of treatment	Bupropion SR capsules, with goal dose of 300 mg/day, for 6 weeks of treatment. Contingency Management is not provided in this arm. Bupropion SR: Bupropion SR, with goal dose 300 mg/day, for 6 weeks of active treatment	Placebo capsules, matched in appearance to Bupropion SR capsules, for 6 weeks of treatment. Contingency Management is not provided in this arm. Placebo: Placebo, matched in appearance to Bupropion SR, for 6 weeks of treatment
Period Title: Overall Study
STARTED	37	36	29	32
COMPLETED	17	18	11	18
NOT COMPLETED	20	18	18	14

Baseline Characteristics

Arm/Group Title	Bupropion SR + Contingency Management	Placebo + Contingency Management	Bupropion SR + No Contingency Management	Placebo + No Contingency Management	Total
Arm/Group Description	Bupropion SR capsules, with goal dose of 300 mg/day, for 6 weeks of treatment. Contingency Management, with escalating rewards for abstinence (and re-sets for non-abstinence) at twice-weekly visits. Bupropion SR: Bupropion SR, with goal dose 300 mg/day, for 6 weeks of active treatment Contingency Management: Contingency Management provided at twice-weekly visits during the 6-week active treatment. Escalating schedule, with resets, reinforcing smoking abstinence.	Placebo capsules, matched in appearance to Bupropion SR capsules, for 6 weeks of treatment. Contingency Management, with escalating rewards for abstinence (and re-sets for non-abstinence) at twice-weekly visits. Contingency Management: Contingency Management provided at twice-weekly visits during the 6-week active treatment. Escalating schedule, with resets, reinforcing smoking abstinence. Placebo: Placebo, matched in appearance to Bupropion SR, for 6 weeks of treatment	Bupropion SR capsules, with goal dose of 300 mg/day, for 6 weeks of treatment. Contingency Management is not provided in this arm. Bupropion SR: Bupropion SR, with goal dose 300 mg/day, for 6 weeks of active treatment	Placebo capsules, matched in appearance to Bupropion SR capsules, for 6 weeks of treatment. Contingency Management is not provided in this arm. Placebo: Placebo, matched in appearance to Bupropion SR, for 6 weeks of treatment	Total of all reporting groups
Overall Participants	37	36	29	32	134
Age (Count of Participants)
<=18 years	17 45.9%	16 44.4%	14 48.3%	15 46.9%	62 46.3%
Between 18 and 65 years	20 54.1%	20 55.6%	15 51.7%	17 53.1%	72 53.7%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	18.4 (1.9)	18.4 (1.9)	18.1 (1.9)	19 (1.8)	18.5 (1.9)
Sex: Female, Male (Count of Participants)
Female	16 43.2%	14 38.9%	11 37.9%	15 46.9%	56 41.8%
Male	21 56.8%	22 61.1%	18 62.1%	17 53.1%	78 58.2%

Outcome Measures

1. Primary Outcome

Title	Biologically-verified 7-day Point Prevalence Smoking Abstinence
Description	Self-reported abstinence for the past 7 days, confirmed by urine cotinine ≤100 ng/mL
Time Frame	End of treatment (week 6)

Outcome Measure Data

Analysis Population Description

Intent-to-treat analysis

Arm/Group Title	Bupropion SR + Contingency Management	Placebo + Contingency Management	Bupropion SR + No Contingency Management	Placebo + No Contingency Management
Arm/Group Description	Bupropion SR capsules, with goal dose of 300 mg/day, for 6 weeks of treatment. Contingency Management, with escalating rewards for abstinence (and re-sets for non-abstinence) at twice-weekly visits. Bupropion SR: Bupropion SR, with goal dose 300 mg/day, for 6 weeks of active treatment Contingency Management: Contingency Management provided at twice-weekly visits during the 6-week active treatment. Escalating schedule, with resets, reinforcing smoking abstinence.	Placebo capsules, matched in appearance to Bupropion SR capsules, for 6 weeks of treatment. Contingency Management, with escalating rewards for abstinence (and re-sets for non-abstinence) at twice-weekly visits. Contingency Management: Contingency Management provided at twice-weekly visits during the 6-week active treatment. Escalating schedule, with resets, reinforcing smoking abstinence. Placebo: Placebo, matched in appearance to Bupropion SR, for 6 weeks of treatment	Bupropion SR capsules, with goal dose of 300 mg/day, for 6 weeks of treatment. Contingency Management is not provided in this arm. Bupropion SR: Bupropion SR, with goal dose 300 mg/day, for 6 weeks of active treatment	Placebo capsules, matched in appearance to Bupropion SR capsules, for 6 weeks of treatment. Contingency Management is not provided in this arm. Placebo: Placebo, matched in appearance to Bupropion SR, for 6 weeks of treatment
Measure Participants	37	36	29	32
Number [participants]	10 27%	3 8.3%	3 10.3%	3 9.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bupropion SR + Contingency Management, Placebo + No Contingency Management
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.07
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.6
	Confidence Interval	(2-Sided) 95%; 0.9 to 14.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Full study period (randomization through week 12 post-treatment follow-up visit)
Arm/Group Title	Bupropion SR + Contingency Management		Placebo + Contingency Management		Bupropion SR + No Contingency Management		Placebo + No Contingency Management
Arm/Group Description	Bupropion SR capsules, with goal dose of 300 mg/day, for 6 weeks of treatment. Contingency Management, with escalating rewards for abstinence (and re-sets for non-abstinence) at twice-weekly visits. Bupropion SR: Bupropion SR, with goal dose 300 mg/day, for 6 weeks of active treatment Contingency Management: Contingency Management provided at twice-weekly visits during the 6-week active treatment. Escalating schedule, with resets, reinforcing smoking abstinence.		Placebo capsules, matched in appearance to Bupropion SR capsules, for 6 weeks of treatment. Contingency Management, with escalating rewards for abstinence (and re-sets for non-abstinence) at twice-weekly visits. Contingency Management: Contingency Management provided at twice-weekly visits during the 6-week active treatment. Escalating schedule, with resets, reinforcing smoking abstinence. Placebo: Placebo, matched in appearance to Bupropion SR, for 6 weeks of treatment		Bupropion SR capsules, with goal dose of 300 mg/day, for 6 weeks of treatment. Contingency Management is not provided in this arm. Bupropion SR: Bupropion SR, with goal dose 300 mg/day, for 6 weeks of active treatment		Placebo capsules, matched in appearance to Bupropion SR capsules, for 6 weeks of treatment. Contingency Management is not provided in this arm. Placebo: Placebo, matched in appearance to Bupropion SR, for 6 weeks of treatment
All Cause Mortality
	Bupropion SR + Contingency Management		Placebo + Contingency Management		Bupropion SR + No Contingency Management		Placebo + No Contingency Management
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/37 (0%)		0/36 (0%)		0/29 (0%)		0/32 (0%)
Serious Adverse Events
	Bupropion SR + Contingency Management		Placebo + Contingency Management		Bupropion SR + No Contingency Management		Placebo + No Contingency Management
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/37 (0%)		0/36 (0%)		0/29 (0%)		0/32 (0%)
Other (Not Including Serious) Adverse Events
	Bupropion SR + Contingency Management		Placebo + Contingency Management		Bupropion SR + No Contingency Management		Placebo + No Contingency Management
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/37 (59.5%)		14/36 (38.9%)		25/29 (86.2%)		15/32 (46.9%)
General disorders
Other	4/37 (10.8%)	4	6/36 (16.7%)	6	3/29 (10.3%)	3	5/32 (15.6%)	5
Nervous system disorders
Headache	12/37 (32.4%)	12	5/36 (13.9%)	5	6/29 (20.7%)	6	5/32 (15.6%)	5
Psychiatric disorders
Insomnia	2/37 (5.4%)	2	0/36 (0%)	0	9/29 (31%)	9	5/32 (15.6%)	5
Irritability	8/37 (21.6%)	8	3/36 (8.3%)	3	5/29 (17.2%)	5	0/32 (0%)	0
Vivid dreams	1/37 (2.7%)	1	0/36 (0%)	0	8/29 (27.6%)	8	0/32 (0%)	0

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.