Varenicline for Nicotine Vaping Cessation in Adolescents

NCT ID: NCT05367492

Last Updated: 2025-04-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 261 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-22
• Study Completion Date: 2024-05-28

Brief Summary

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.

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.

Conditions

Vaping; Nicotine Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Double Blind Varenicline

Intervention Type: DRUG

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

QuitVaping

Intervention Type: BEHAVIORAL

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 Quitting

Intervention Type: BEHAVIORAL

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.

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.

Group Type: PLACEBO_COMPARATOR

Double Blind Placebo

Intervention Type: DRUG

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

QuitVaping

Intervention Type: BEHAVIORAL

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 Quitting

Intervention Type: BEHAVIORAL

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.

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.

Group Type: ACTIVE_COMPARATOR

This Is Quitting

Intervention Type: BEHAVIORAL

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.

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

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.

Intervention Type: 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.

Intervention Type: BEHAVIORAL

Other Intervention Names

TIQ

Eligibility Criteria

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.

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Anne Eden Evins

Founder Director, Center for Addiction Medicine and Director for Faculty Development, Department of Psychiatry; Cox Family Professor of Psychiatry in the Field of Addiction Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Eden Evins, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Randi Schuster, PhD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Center for Addiction Medicine

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 37009114 (View on PubMed)

Evins AE, Cather C, Reeder HT, Evohr B, Potter K, Pachas GN, Gray KM, Levy S, Rigotti NA, Iroegbulem V, Dufour J, Casottana K, Costello MA, Gilman JM, Schuster RM. Varenicline for Youth Nicotine Vaping Cessation: A Randomized Clinical Trial. JAMA. 2025 Jun 3;333(21):1876-1886. doi: 10.1001/jama.2025.3810.

Reference Type: DERIVED

PMID: 40266580 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R01DA052583

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2020P002774

Identifier Type: -

Identifier Source: org_study_id