Varenicline for Nicotine Vaping Cessation in Adolescents

NCT05367492 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: 2020P002774R01DA052583
• Study Type: interventional
• Target: 261
• Locations: 1 country
• Sites: 1

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.

Conditions

Vaping; Nicotine Dependence

Keywords

Vaping; Nicotine; Adolescents; Cessation; Varenicline

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

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

  Study week 12

• Continuous Nicotine Vaping Abstinence Over Study Weeks 9 to 24

  Study weeks 9, 10, 11, 12, 16, 20, 24

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

  Study weeks 1-12

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

  Study weeks 1-12

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

  Study weeks 4, 8, 12

Study Arms (3)

Double Blind Varenicline (V + BC)

EXPERIMENTAL

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; Behavioral: QuitVaping; Behavioral: This Is Quitting

Double Blind Placebo (P + BC)

PLACEBO COMPARATOR

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.

Drug: Double Blind Placebo; Behavioral: QuitVaping; Behavioral: This Is Quitting

Single Blind Enhanced Usual Care (EUC)

ACTIVE COMPARATOR

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

Interventions

Double Blind Varenicline 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

Double Blind Varenicline (V + BC)

Double Blind Placebo 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

Double Blind Placebo (P + BC)

QuitVaping 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.

Double Blind Placebo (P + BC); Double Blind Varenicline (V + BC)

This Is Quitting 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.

Also known as: TIQ

Double Blind Placebo (P + BC); Double Blind Varenicline (V + BC); Single Blind Enhanced Usual Care (EUC)

Eligibility Criteria

• Age: 16 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Center for Addiction Medicine

Boston, Massachusetts, 02114, United States

Location

Related Publications (3)

• 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.

  PMID: 37009114 BACKGROUND

• Gilman JM, Cather C, Reeder HT, Evohr B, Pachas GN, Gray KM, McClure EA, Schuster RM, Evins AE. Cannabis Use and Nicotine Vaping Cessation Outcomes: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2025 Dec 1;8(12):e2547799. doi: 10.1001/jamanetworkopen.2025.47799.

  PMID: 41385228 DERIVED

• 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.

  PMID: 40266580 DERIVED

MeSH Terms

Conditions

Vaping; Tobacco Use Disorder

Condition Hierarchy (Ancestors)

Smoking; Behavior; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Limitations and Caveats

The sample size was underpowered to detect the observed difference in the exploratory comparison between P+ BC and EUC. Results may not generalize to those who regularly use both combustible tobacco and vaped nicotine.

Results Point of Contact

• Title: A. Eden Evins, MD, MPH
• Organization: Massachusetts General Hospital

aeevins@mgh.harvard.edu

617-643-4679

Study Officials

• Eden Evins, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Randi Schuster, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Eligible participants will be assigned to one of three groups using a computer-generated randomization code conducted by MGH Research Pharmacy personnel with no other interactions with participants. The full randomization code of the two double blind treatment arms (arm 1 active varenicline and arm 2 identical placebo), and the single blind EUC arm (arm 3) will be held in the MGH research pharmacy and available to study PIs for urgent medical need only. Participants, investigators and outcome assessors will be fully blind to all 3 arms. A partial randomization code identifying those assigned to double-blind treatment (a combined list of study IDs assigned to either study arm 1 or 2) vs single blind EUC (study arm 3) will be held by a scheduler who is not associated with outcomes assessment, data analysis or interpretation. Assignment to Arm 3, single blind EUC only, will be masked to investigators and outcomes assessors.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: 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

Model Details: Up to 300 participants will be consented and approximately 225 participants will be randomized in a double blind, placebo-controlled, parallel-group trial comparing vaping abstinence rates in participants randomly assigned to (1) varenicline added to behavioral and texting support for vaping cessation (V+BC) and (2) identical placebo added to behavioral and texting support for vaping cessation (P+BC) (primary comparison). Exploratory secondary comparisons will be made between double blind arms 1 and 2 and the single blind (3) enhanced usual care arm.

Study Record Dates

• First Submitted: May 4, 2022
• First Posted: May 10, 2022
• Study Start: June 22, 2022
• Primary Completion: March 20, 2024
• Study Completion: May 28, 2024
• Last Updated: April 27, 2025
• Results First Posted: April 27, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Beginning 3 months and ending 5 years following manuscript publication.
• 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.

Locations

US (1)