Varenicline for Nicotine Vaping Cessation in Adolescents (ViVA)

Randomized Controlled Trial of Varenicline for Cessation of Nicotine Vaping in Adolescent Non-smokers

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.

Study Overview

• Status: Completed
• Conditions: Nicotine Dependence; Vaping
• Intervention / Treatment: Drug: Double Blind Varenicline; Behavioral: QuitVaping; Behavioral: This Is Quitting; Drug: Double Blind Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 261
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Center for Addiction Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Double Blind Varenicline (V + BC); Participants will...; Receive the drug varenicline, in tablet form, up to 1 mg BID for 12 weeks.; Attend QuitVaping behavioral support sessions, completed in-person or via video-conferencing, once per week for 12 weeks.; Be encouraged to sign up for This Is Quitting (TIQ), a text message vaping cessation program for adolescents.	Drug: Double Blind Varenicline; 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; Behavioral: QuitVaping; 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.; Behavioral: This Is Quitting; 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.; Other Names: TIQ
Placebo Comparator: Double Blind Placebo (P + BC); Participants will...; Receive placebo tablets, identical in appearance to varenicline, up to 1 mg BID for 12 weeks.; Attend QuitVaping behavioral support sessions, completed in-person or via video-conferencing, once per week for 12 weeks.; Be encouraged to sign up for This Is Quitting (TIQ), a text message vaping cessation program for adolescents.	Behavioral: QuitVaping; 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.; Behavioral: This Is Quitting; 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.; Other Names: TIQ; Drug: Double Blind Placebo; 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
Active Comparator: Single Blind Enhanced Usual Care (EUC); Participants will...; Receive NO drug intervention.; Attend NO behavioral support sessions.; Be encouraged to sign up for This Is Quitting (TIQ), a text message vaping cessation program for adolescents.	Behavioral: This Is Quitting; 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.; Other Names: TIQ

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Assessments at study weeks 9, 10, 11, and 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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).	Study weeks 1-12

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Eden Evins, MD, Massachusetts General Hospital; Principal Investigator: Randi Schuster, PhD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Schuster RM, Cather C, Pachas GN, Nielsen L, Iroegbulem V, Dufour J, Potter K, Levy S, Gray KM, Evins AE. A randomized controlled trial of varenicline and brief behavioral counseling delivered by lay counselors for adolescent vaping cessation: Study protocol. Front Psychiatry. 2023 Mar 15;14:1083791. doi: 10.3389/fpsyt.2023.1083791. eCollection 2023.

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2022
• Primary Completion (Actual): March 20, 2024
• Study Completion (Actual): May 28, 2024

Study Registration Dates

• First Submitted: May 4, 2022
• First Submitted That Met QC Criteria: May 9, 2022
• First Posted (Actual): May 10, 2022

Study Record Updates

• Last Update Posted (Actual): April 27, 2025
• Last Update Submitted That Met QC Criteria: April 15, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Adolescents; Nicotine; Varenicline; Cessation; Vaping
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Tobacco Use Disorder; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Cholinergic Agents; Nicotinic Agonists; Cholinergic Agonists; Varenicline
• Other Study ID Numbers: 2020P002774; R01DA052583 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data that support the findings of this study are available upon request. Data will include de-identified individual patient-level data, a data dictionary, and analytic code. Investigators proposing to use the data must execute a data use agreement with Massachusetts General Hospital and have approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, before data is shared. Data will be available within three months of manuscript publication. Requests for data should be sent to aeevins@mgh.harvard.edu or rschuster@mgh.harvard.edu.
• IPD Sharing Time Frame: Beginning 3 months and ending 5 years following manuscript publication.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal to achieve aims in the approved proposal. Data use agreement and approval from an Institutional Review Board, Independent Ethics Committee, or Research Ethics Board are required.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No