Varenicline for Nicotine Vaping Cessation in Adolescents

Massachusetts General Hospital261 enrolled

Overview

The study will test the hypothesis that varenicline, when added to behavioral and texting support for vaping cessation, will improve vaping abstinence rates in adolescents dependent on vaped nicotine over placebo plus behavioral and texting support for vaping cessation. Approximately 225 adolescents will be randomly assigned to one of three arms (1) varenicline up to 1 mg bid for 12 weeks plus behavioral and texting support for vaping cessation (V+BC), (2) identical appearing placebo plus behavioral and texting support (P+BC) and (3) enhanced usual care (EUC). The primary comparison will be the double-blind, placebo-controlled comparison of vaping cessation rates in those assigned to varenicline vs placebo.

Up to 300 adolescents, aged 16-25, who vape, do not smoke regularly, and want to quit vaping will be consented; approximately 225 eligible participants will be randomly assigned to a double blind, placebo-controlled intervention consisting of (1) varenicline or (2) identical placebo, up to 1 mg bid for 12 weeks, plus behavioral and texting support for adolescent vaping cessation or to (3) enhanced usual care. The primary comparison of interest is the double blind, placebo-controlled efficacy comparison of those assigned to (1) varenicline vs (2) placebo on vaping abstinence outcomes. The secondary comparison of placebo plus behavioral and texting support vs. EUC will estimate the efficacy of behavioral and texting support for vaping cessation in this population. The secondary comparison of varenicline plus behavioral and texting support vs EUC will estimate of the efficacy of varenicline treatment plus behavioral and texting support for vaping cessation in this population vs no treatment, the most common vaping cessation intervention. All participants will complete enrollment and baseline visits, and six monthly assessment visits. Those assigned to double blind intervention (study arms 1 or 2) will also complete 12 weekly behavioral support sessions. Assessors will be blind to intervention assignment (arm 1 or 2) vs EUC (arm 3) assignment. Among those assigned to the V+BC or P+BC intervention arms, study staff and participants will be blind to active varenicline vs placebo assignment, such that among those assigned to intervention (arm 1 or 2), assignment to study drug will be double blind. For those assigned a double blind intervention arm, study staff will distribute varenicline or identical appearing placebo and give instructions use at weeks 0, 2, 4 and 8. Participants will be asked to bring all empty and unused study medication at each in-person study visit through Week 12. The enrollment visit will consist of questionnaires, diagnostic assessments, vitals, saliva and urine samples. The baseline visit will consist of questionnaires, a saliva sample for cotinine concentration, and randomization. Monthly visits will consist of interviews, questionnaires and a saliva and urine sample. Weekly treatment meetings for participants assigned to arms 1 or 2 will consist of cognitive behavioral support and questionnaires.

Interventions

Double Blind VareniclineDRUG

For participants 16-17 years old, ≤ 55 kg: * 0.5 mg once daily for 7 days, then * 0.5 mg twice daily for 11 weeks For participants 16-17 years old, \>55 kg: * 0.5 mg once daily or 3 days, * 0.5 mg twice daily for 4 days * 1.0 mg twice daily for 11 weeks For participants 18+ years old: * 0.5 mg once daily or 3 days, * 0.5 mg twice daily for 4 days * 1.0 mg twice daily for 11 weeks

Double Blind PlaceboDRUG

For participants 16-17 years old, ≤ 55 kg: * 0.5 mg once daily for 7 days, then * 0.5 mg twice daily for 11 weeks For participants 16-17 years old, \>55 kg: * 0.5 mg once daily or 3 days, * 0.5 mg twice daily for 4 days * 1.0 mg twice daily for 11 weeks For participants 18+ years old, regardless of weight: * 0.5 mg once daily or 3 days, * 0.5 mg twice daily for 4 days * 1.0 mg twice daily for 11 weeks

QuitVapingBEHAVIORAL

QuitVaping is a manualized intervention based on the American Lung Association smoking cessation program modified with adolescent appropriate content and language for vaping cessation from the vaping section of teen.smokefree.gov and the Truth Initiative. These behavioral support sessions will be delivered weekly during the 12-week treatment phase via videoconference or in- person.

This Is QuittingBEHAVIORAL

A free, publicly available text message vaping cessation program from Truth Initiative, designed specifically to help adolescents who vape nicotine quit. Participants who set a quit date receive messages for a week preceding it and 30 days afterward that include encouragement and support, skill- and self-efficacy building exercises, coping strategies, and information about the risks of vaping, benefits of quitting and cutting down to quit.

Eligibility

Sex: ALLMin age: 16 YearsMax age: 25 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Ages 16-25, inclusive; * Self-report of daily or near daily nicotine vaping for the prior ≥ 3 months and semi-quantitative saliva screening for cotinine positive for recent nicotine use; * Nicotine dependence as defined by a score ≥4 on the 10-item E-cigarette Dependence Inventory (ECDI), or report of persistent use despite negative consequences, or prior failed quit attempts; * Self-report of no regular combusted tobacco use in the past 2 months at enrollment and exhaled CO \<10 ppm; * Total body weight at enrollment ≥35 kg (77 lbs); * Report willingness to try varenicline to stop vaping; * Able to understand study procedures and read and write in English; * Have a parent or legal guardian who is able and willing to provide written informed consent (if under the age of 18); * Competent and willing to provide written informed consent (if age 18+) or assent (if under 18); * For participants who could become pregnant: negative urine pregnancy test at enrollment and agree to use effective contraception (e.g., abstinence, hormonal contraception, intra-uterine device, sterilization, or double barrier contraception) during the study. Exclusion Criteria: * Use of a smoking cessation medication in the prior month (nicotine patch, gum, nasal spray, or inhaler, varenicline, bupropion); * Unwilling to abstain during the study from using smoking cessation aids other than those provided by the study; * Unstable medical condition, epilepsy, severe renal impairment; * Inpatient psychiatric hospitalization in the prior 6 months, serious suicidal ideation or suicide attempt within 6 months of enrollment, recent active suicidal ideation or suicidal behavior identified at enrollment or baseline visits; * Evidence of active problem substance use severe enough to compromise ability to safely participate, in the investigator's opinion; * Prior adverse drug reaction to varenicline; * Unwilling to provide urine samples; * Any condition or situation that would, in the investigator's opinion, make it unlikely that the participant could adhere safely to the study protocol; * Ward of the state.

Outcomes

Primary Outcomes

Continuous 4-week Nicotine Vaping Abstinence at End of Treatment (Weeks 9-12)

Point-prevalence abstinence from e-cigarette use was defined as self-report of no e-cigarette use since the last visit, bioverified by saliva cotinine \<30 ng/ml. Continuous abstinence is defined as observed point-prevalence abstinence over specified study visits at weeks 9, 10, 11 and 12. Visits with self-reported abstinence missing bioverification were treated as missing, with missingness addressed via multiple imputation.

Time frame: Assessments at study weeks 9, 10, 11, and 12

Secondary Outcomes

Seven-Day Point-Prevalence Nicotine Vaping Abstinence at End of Treatment (Week 12)

Point-prevalence abstinence from e-cigarette use was defined as self-report of no e-cigarette use since the last visit, bioverified by saliva cotinine \<30 ng/ml. Visits with self-reported abstinence missing bioverification were treated as missing, with missingness addressed via multiple imputation.

Time frame: Study week 12

Continuous Nicotine Vaping Abstinence Over Study Weeks 9 to 24

Point-prevalence abstinence from e-cigarette use was defined as self-report of no e-cigarette use since the last visit, bioverified by saliva cotinine \<30 ng/ml. Continuous abstinence defined as observed point-prevalence abstinence over specified study visits at weeks 9, 10, 11, 12, 16, 20, and 24. Visits with self-reported abstinence missing bioverification were treated as missing, with missingness addressed via multiple imputation.

Time frame: Study weeks 9, 10, 11, 12, 16, 20, 24

Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12)

Minnesota Nicotine Withdrawal Scale (MNWS) total scores over study weeks 1 to 12. The MNWS is an 8-item measure assessing the severity of nicotine withdrawal symptoms. Items are scored on an ordinal scale from 0 ("not at all") to 4 ("extreme") with total scores ranging from 0 to 32. Higher scores indicate greater severity of nicotine withdrawal symptoms. Missingness due to missed visits and/or dropout was addressed via multiple imputation.

Time frame: Study weeks 1-12

Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12)

Summed scores from the Questionnaire of Vaping Craving (QVC) over Study Weeks 1 to 12. The QVC is a 10-item self-rated validated measure (ranging from 10 to 70) of vaping craving that examines desire and intent to vape and anticipation of positive outcomes related to e-cigarette use, with higher scores indicating greater cravings to vape. Missingness due to missed visits and/or dropout are addressed with multiple imputation.

Time frame: Study weeks 1-12

Mood and Anxiety Symptoms Questionnaire (MASQ-D30) General Distress Subscore (Weeks 4, 8, and 12)

Summed scores from the General Distress Subscale of the 30-Item Mood and Anxiety Symptoms Questionnaire (MASQ-D30) over Study Weeks 4,8, and 12. The General Distress subscale of the MASQ-D30 is a 10-item self-rated validated measure (ranging from 10 to 50) of non-specific symptoms of general distress or negative affect, with higher scores indicating a greater degree of general distress. Missingness due to missed visits and/or dropout was addressed with multiple imputation.

Time frame: Study weeks 4, 8, 12

Neuropsychiatric Adverse Event Inventory (NAEI) Elicited Adverse Events by Week 12

The Neuropsychiatric Adverse Event Inventory (NAEI) is a structured interview used to assess neuropsychiatric adverse events. This outcome reports on the number of participants who reported at least one adverse event on the NAEI between the first study week (Week 1) to the end of treatment (Week 12).

Time frame: Study weeks 1-12

Varenicline for Nicotine Vaping Cessation in Adolescents

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes