Varenicline for Adolescent Smoking Cessation

Study Overview
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Brief Summary
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This is a placebo-controlled smoking cessation treatment study for adolescents ages 14-21. After assessment and inclusion into the study, participants will be randomized to receive a 12-week double blind course of varenicline or placebo.

Detailed Description
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The objective of this protocol is to examine the efficacy and safety of varenicline for smoking cessation in adolescents. The guiding design philosophy was to model the adult smoking cessation literature (allowing for indirect comparisons of efficacy in different populations) while fine-tuning some elements specifically geared for adolescents. After assessment and inclusion into the study, participants will be randomized to receive a 12-week double blind course of varenicline or placebo. Participants will provide smoking self-report (cigarettes per day) throughout the study. Biological confirmation with carbon monoxide breathalyzer will occur at all visits, and urine cotinine measurement will occur at key time points (baseline, end of treatment and final post-treatment follow-up). Psychiatric/medical visits will occur weekly throughout active treatment to systematically monitor safety and tolerability. After the 12-week treatment course, participants will return for 3 post-treatment follow-up visits (Week 13, Week 18, and Week 26).

Official Title
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A Randomized Controlled Trial of Varenicline for Adolescent Smoking Cessation

Conditions
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Nicotine Dependence

Intervention / Treatment
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* Drug: Varenicline
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 14-21 Daily smoker for ≥6 months Desire to quit smoking, with at least one prior failed quit attempt and willingness to participate in a treatment study If under age 18, parent(s) or guardian(s) able to participate in informed consent and initial assessment (unless the participant provides evidence of emancipated status) If female, agreement to use birth control (any form of hormonal contraception such as Depo-Provera, daily oral contraception, transdermal patch, or Nuva-ring; intrauterine device; sterilization; or double barrier contraception, which is a combination of any two of the following methods: condoms, spermicide, diaphragm) to avoid pregnancy Exclusion Criteria: Lifetime history of any DSM-IV-TR mood or psychotic disorder (e.g., major depressive disorder, bipolar disorder, schizophrenia) Lifetime history of suicidality, homicidality, or clinically significant hostility/aggression Current substance dependence, other than nicotine Current unstable major medical disorder Current pregnancy or breastfeeding Current use of medications with smoking cessation efficacy Known hypersensitivity to varenicline

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: varenicline<br>Participants >55 kg will take varenicline 0.5 mg once daily for 3 days, titrated to 0.5 mg twice daily for 4 days, titrated to 1 mg twice daily for 11 weeks. Participants ≤55 kg will take varenicline 0.5 mg once daily for 7 days, titrated to 0.5 mg twice daily for 11 weeks. | Drug: Varenicline<br>* participants >55 kg will take varenicline/placebo 0.5 mg once daily for 3 days, titrated to 0.5 mg twice daily for 4 days, titrated to 1 mg twice daily thereafter. Participants ≤55 kg will take varenicline/placebo 0.5 mg once daily for 7 days, titrated to 0.5 mg twice daily thereafter.<br>* Other names: Chantix;|
| Placebo Comparator: placebo<br>Participants >55 kg will take placebo 0.5 mg once daily for 3 days, titrated to 0.5 mg twice daily for 4 days, titrated to 1 mg twice daily for 11 weeks. Participants ≤55 kg will take placebo 0.5 mg once daily for 7 days, titrated to 0.5 mg twice daily for 11 weeks. | Drug: placebo<br>* participants >55 kg will take varenicline/placebo 0.5 mg once daily for 3 days, titrated to 0.5 mg twice daily for 4 days, titrated to 1 mg twice daily thereafter. Participants ≤55 kg will take varenicline/placebo 0.5 mg once daily for 7 days, titrated to 0.5 mg twice daily thereafter.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Cotinine-confirmed 7-day Point Prevalence Abstinence at the End of Treatment | Self-reported 7-day cigarette abstinence, confirmed by urine corinne ≤50 ng/mL at the end-of-treatment (week 12) visit | 7 days at end of treatment | 
| Number of Participants Experiencing Treatment-emergent Adverse Events | Clinician-collected adverse events (regardless of relatedness to medication) occurring at any point after randomization and initiation of treatment. | 26 weeks (12 weeks of treatment plus full post-treatment follow-up) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Visits With Abstinence During Treatment | Self-reported between-visit abstinence at weekly visits during treatment (reported as percentage of total possible visits across all participants at which participants self-reported abstinence). Missing data were imputed to non-abstinence. | 12 weeks (all of active treatment) | 
| Percentage of Post-treatment Visits With Abstinence | Self-reported abstinence at post-treatment follow-up visits (reported as percentage of total possible post-treatment follow-up visits at which abstinence in the prior week was self-reported). Missing data were imputed to non-abstinence. | One week abstinence at the Week 16 and Week 26 post-treatment follow-up visits | 
| Number of Participants Achieving 7+ Days Abstinence at Any Point During Treatment | Number of participants achieving 7+ days of self-reported abstinence at any point during active treatment | 12 weeks of active treatment |