Varenicline For Nicotine Vaping Cessation In Non Smoker Vaper Adolescents (Pilot)

The pilot study used apo-varenicline under temp FDA authorization. When varenicline was available an IND exemption was granted to enroll children, IRB approved a trial of varenicline in participants ages 16-25 June 27, 2022, the pilot was terminated

The Investigators propose a randomized, placebo-controlled trial to test the hypothesis that varenicline added to group behavioral and texting support will be well tolerated and improve vaping cessation rates among nicotine dependent adolescents who vape, do not smoke regularly, and are willing to try treatment to stop vaping compared to placebo added to group behavioral and texting support. The study will consist of a three-arm randomized, placebo-controlled, parallel-group study of (1) varenicline up to 1 mg bid for 12 weeks added to behavioral and texting support compared with (2) behavioral and texting support and placebo and (3) monitoring only. The primary comparison will be of vaping cessation rates in those assigned to varenicline vs placebo.To do this, the investigators propose to enroll 300 adolescents aged 16-25 who meet eligibility criteria.

Enrollees will include 300 nicotine dependent adolescents aged 16-25, who vape, do not smoke, and want to quit vaping. The study will will consist of a three-arm randomized, placebo-controlled, parallel-group study of (1) varenicline up to 1 mg bid for 12 weeks added to behavioral and texting support for adolescent vaping cessation or (2) behavioral and texting support and placebo or (3) monitoring only. The primary comparison of interest is efficacy of (1) varenicline vs (2) placebo arms on vaping abstinence outcomes. The study consists of one enrollment visit, one baseline visit, twelve weekly individual treatment and assessment sessions, and six monthly visits at weeks 4, 8, 12, 16, 20 and 24 weeks. At the enrollment visit, participants will complete interviews, questionnaires and diagnostic assessments, as well as saliva and urine sample and vitals. At the baseline visit, participants will complete several interviews, questionnaires, provide a saliva sample for cotinine measurement, and be randomized to the varenicline plus behavioral treatment group, the placebo plus behavioral treatment group, or monitoring-only group. Study staff will distribute varenicline or identically appearing placebo with instructions on how to take the study medication at weeks 0, 2, 4 and 8. Participants will be instructed to bring all empty and unused study medication at each in-person study visit through Week 12. At the weekly treatment meetings, participants will participate in cognitive behavioral therapy and complete questionnaires. Monthly visits will consist of interviews, questionnaires and a saliva and urine sample.

This a 3-arm, randomized, placebo-controlled, parallel-group design of (1) varenicline up to 1 mg bid for 12 weeks added to behavioral and texting support vaping cessation compared or (2) behavioral and texting support and placebo or (3) monitoring only.

Eligible participants will be randomly assigned in a 1:1:1 ratio, in blocks of 6, to double-blind varenicline, identical placebo prepared by the MGH research pharmacy or monitoring (i.e., assessment only). Randomization will be computer generated by the MGH Research Pharmacy personnel with no other interactions with study staff or participants. The full randomization code (drug, placebo, monitoring) will be held in the MGH research pharmacy and available to study PI only in the case of urgent medical need. A partial randomization code (treatment vs monitoring) will be held by the interventionist at the Center for Addiction Medicine. Participants, investigators and outcome assessor will remain fully blind to all 3 arms.

Participants will receive varenicline 0.5 mg once daily on days 1-3, 0.5 mg twice daily on days 4-7 and starting on day 8, 1 mg twice daily for a total of 12 weeks added to 12 weeks of group behavioral and texting support specifically designed for teen vaping cessation

Participants will receive identical placebo 0.5 mg once daily on days 1-3, 0.5 mg twice daily on days 4-7 and starting on day 8, 1 mg twice daily for a total of 12 weeks added to 12 weeks of group behavioral and texting support specifically designed for teen vaping cessation

Participants will attend weekly and monthly sessions that will only consist of assessments. No study medication, no behavioral or texting support.

varenicline: 0.5 mg once daily on days 1-3, 0.5 mg twice daily on days 4-7 and starting on day 8, 1 mg twice daily for a total of 12 weeks

Identical placebo: 0.5 mg once daily on days 1-3, 0.5 mg twice daily on days 4-7 and starting on day 8, 1 mg twice daily for a total of 12 weeks

Percentage of participants with continuous nicotine vaping abstinence from week 9 through end of treatment

Those assigned to varenicline and group behavioral and texting support will have a higher rate of cotinine verified, continuous nicotine vaping abstinence from study week 9 to end of treatment as operationalized by self-report of no nicotine vaping since the last study visit and urinary cotinine <50 ng/ml at each study visit in the designated timeframe.

Percentage of participants with continuous nicotine vaping abstinence from week 9 through end of follow-up

Those assigned to varenicline and group behavioral and texting support will have a higher rate of cotinine verified, continuous nicotine vaping abstinence from study week 9 to end of follow-up as operationalized by self-report of no nicotine vaping since the last study visit and urinary cotinine <50 ng/ml at each study visit in the designated timeframe.

Those assigned to varenicline will have greater reduction in vaped nicotine product exposure than those assigned to placebo as determined by urine cotinine at each visit

Those assigned to varenicline will have earlier onset of abstinence. Self-report verified by urine cotinine at each study visit.

Those assigned to varenicline will have longer latency to first lapse. Self-report verified by urine cotinine at each study visit.

Those assigned to varenicline will have longer latency to relapse. Self-report verified by urine cotinine at each study visit.

Those assigned to varenicline will have a longer duration of abstinence. Self-report verified by urine cotinine at each study visit.

Those assigned to varenicline will have greater total number of days of vaping abstinence. Total number of days vape-free by self-report verified by urine cotinine at each study visit will be compared.

Adverse events are assessed via standardized questions prompting participants to report any changes in their physical or mental health.

Symptoms will be assessed using the Minnesota Withdrawal Scale (MNWS), a 9-item self-rated scale of urge to smoke (craving); depressed mood; irritability, frustration or anger; anxiety; difficulty concentrating; restlessness; increased appetite; difficulty going to sleep; difficulty staying asleep, on an ordinal scale from 0 (not at all) to 4 (extreme). It will be administered at enrollment and each subsequent study visit.

The scale used to measure intensity of craving will be a Visual Analogue Scale 0 (no desire at all) - 7 (unable to resist)

Severity of nicotine cravings will be assessed using the Questionnaire of Vaping Craving (QVC), a 10-item, valid and reliable measure of vaping craving that queries desire and intent to vape and anticipation of positive outcomes related to e-cigarette use, on an ordinal scale from 1 (strongly agree) to 7 (strongly disagree). It will be administered at enrollment and each subsequent study visit.

As assessed by the Mood and Anxiety Symptoms Questionnaire (MASQ-D30), is a 30-item adaptation of the 96 item MASQ that is quick, valid and reliable assessment of depression and anxiety in adolescents, with answers on a ordinal scale from Not at all/slightly to Extremely. It will be administered at each study visit to follow participants' mood symptoms over time during the intervention and follow up.

Assessed with timeline follow back where individuals report the number of days, times, and amount of alcohol, tobacco, marijuana, and non-medical prescription drugs consumed since last study visit.

Inclusion Criteria: Ages 18-25 inclusive; Self report of daily or near daily nicotine vaping for the prior ≥ 3 months, screening semi-quantitative urine cotinine positive for recent nicotine use, exhaled CO <10 ppm and score ≥4 on the 10-item E-cigarette Dependence Inventory (ECDI); Self-report of no combusted tobacco use in the past 2 months at enrollment; Total body weight at screening ≥35 kg (77 lbs) and Body Mass Index (BMI) ≤35 kg/m2; Report motivation to quit vaping in the next 30 days; Able to understand study procedures and read and write in English; Competent and willing to consent to participate in study procedures. Exclusion Criteria: Use of a smoking cessation medication in the prior month (nicotine patch, gum, nasal spray, or inhaler, varenicline, bupropion); Unwillingness to abstain during the study from using smoking cessation aids other than those provided by the study; Unstable medical condition, epilepsy, severe renal impairment; Evidence of active problem substance use severe enough in the investigator's opinion to compromise ability to safely participate; 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.

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.

Researchers who provide a methodologically sound proposal to achieve aims in the approved proposal. Data access agreement required.