Varenicline for Nicotine Vaping Cessation in Adolescents (ViVA)

• ClinicalTrials.gov Identifier: NCT05367492
• Recruitment Status: Recruiting
• First Posted: May 10, 2022
• Last Update Posted: August 24, 2022
• Sponsor: Massachusetts General Hospital
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): A. Eden Evins, Massachusetts General Hospital

Study Description

Brief Summary:

The study will test the hypothesis that varenicline, when added to group behavioral and texting support for vaping cessation, will improve vaping abstinence rates in adolescents dependent on vaped nicotine over placebo plus group 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 (2) identical appearing placebo plus behavioral and texting support and (3) monitoring only. The primary comparison will be the double-blind, placebo-controlled comparison of vaping cessation rates in those assigned to varenicline vs placebo.

Condition or disease	Intervention/treatment	Phase
Vaping; Nicotine Dependence	Drug: Double Blind Varenicline; Drug: Double Blind Placebo; Behavioral: QuitVaping; Behavioral: This Is Quitting	Phase 4

Detailed Description:

Up to 300 adolescents, aged 16-25, who vape, do not smoke regularly, and want to quit vaping will be enrolled; 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) monitoring only. 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. monitoring only 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 monitoring only 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 monitoring only (arm 3) assignment. Among those assigned to an intervention arm, 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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: 300 participants will be enrolled 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 and (2) identical placebo added to behavioral and texting support for vaping cessation (primary comparison). Exploratory secondary comparisons will be made between double blind arms 1 and 2 and the single blind (3) monitoring only arm.
• Masking: Triple (Participant, Investigator, Outcomes Assessor)

Masking Description

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 monitoring 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 monitoring (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 monitoring only, will be masked to investigators and outcomes assessors.

• Primary Purpose: Treatment
• Official Title: Varenicline for Nicotine Vaping Cessation in Adolescents
• Actual Study Start Date: June 27, 2022
• Estimated Primary Completion Date: December 2025
• Estimated Study Completion Date: December 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Double Bline Varenicline; 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 Name: TIQ
Placebo Comparator: Double Blind Placebo; 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; 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; 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 Name: TIQ
No Intervention: Single Blind Monitoring only; Participants will...; Receive NO drug intervention.; Attend NO behavioral support sessions.; Will not be encouraged to sign up for text message vaping cessation support.

Outcome Measures

Primary Outcome Measures :

1. Continuous 4-week Nicotine Vaping Abstinence at end of treatment [ Time Frame: Study week12 ]
   The percent of participants who self-report nicotine vaping abstinence since the last visit and have cotinine <10 ng/ml, assessed at study weeks 9 - 12. The primary comparison of interest is between the varenicline and placebo arms

Secondary Outcome Measures :

1. Seven-Day Point-Prevalence Nicotine Vaping Abstinence at End of Treatment [ Time Frame: Study week 12 ]
   Percent of participants who self-report nicotine vaping abstinence for 7 days and have cotinine <10 ng/ml at week 12. The primary comparison of interest is between the varenicline and placebo arms.
2. Continuous Nicotine Vaping Abstinence over Study Weeks 9 to 24 [ Time Frame: Study weeks 9, 10, 11, 12, 16, 20, 24 ]
   Percent of participants who self-report nicotine vaping abstinence since the last visit and have cotinine <10 ng/ml, assessed at each visit during study weeks 9 - 24. The primary comparison of interest is between the varenicline and placebo arms.
3. Change in Nicotine Withdrawal symptoms [ Time Frame: Study weeks 1-12 ]
   Change in Nicotine Withdrawal Scale (MNWS) scores over Study Weeks 1 to 12. The MNWS is a 9-item self-rated validated measure (ranging from 0 to 36) of nicotine withdrawal, with higher scores indicating greater severity of withdrawal symptoms. The primary comparison of interest is between the varenicline and placebo arms.
4. Change in Vaping Craving (QVC) [ Time Frame: Study weeks 1-12 ]
   Mean Change in 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. The primary comparison of interest is between the varenicline and placebo arms.
5. Change in General Distress [ Time Frame: Study weeks 1-12 ]
   Mean Change in Summed Scores from the General Distress Subscale of the 30-Item Mood and Anxiety Symptoms Questionnaire (MASQ-D30) over Study Weeks 1 to 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. The primary comparison of interest is between the varenicline and placebo arms.
6. Adverse Events [ Time Frame: Study weeks 1-12 ]
   The number of participants who report at least one adverse event during the interval between the first study week (week 1) to end of treatment (week 12). The primary comparison of interest is between the varenicline and placebo arms.

Eligibility Criteria

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

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) and Body Mass Index (BMI) ≤35 kg/m2;
• 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;
• Lifetime history of schizophrenia or bipolar disorder, 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.

Contacts and Locations

Contacts

Contact: Gladys N Pachas, MD; 6176431991; gpachas1@mgh.harvard.edu

Locations

United States, Massachusetts

Center for Addiction Medicine; Recruiting

Boston, Massachusetts, United States, 02114

Contact: Gladys Pachas, MD 617-643-1991 gpachas1@mgh.harvard.edu

Sponsors and Collaborators

Massachusetts General Hospital

National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Eden Evins, MD; Massachusetts General Hospital
• Principal Investigator: Randi Schuster, PhD; Massachusetts General Hospital

More Information

• Responsible Party: A. 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, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT05367492
• Other Study ID Numbers: 2020P002774; R01DA052583 ( U.S. NIH Grant/Contract )
• First Posted: May 10, 2022
• Last Update Posted: August 24, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices), and the study protocol, statistical analysis plan, analytic code, and informed consent form will be made available to researchers who provide a methodologically sound proposal beginning 3 months and ending 5 years following article publication to achieve aims in the approved proposal. Proposals should be directed to rschuster@mgh.harvard.edu. To gain access, data requestors will need to sign a data access agreement.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Analytic Code
• Time Frame: Beginning 3 months and ending 5 years following article publication.
• Access Criteria: Researchers who provide a methodologically sound proposal to achieve aims in the approved proposal. Data access agreement required.

• 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

Keywords provided by A. Eden Evins, Massachusetts General Hospital:

Vaping; Nicotine; Adolescents; Cessation; Varenicline

Additional relevant MeSH terms:

Tobacco Use Disorder; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Varenicline; Nicotinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs