Nicotine Dependence, Vaping
Conditions
Keywords
Vaping, Nicotine, Adolescents, Cessation, Varenicline
Brief summary
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.
Detailed description
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.
Interventions
DRUGVarenicline
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
DRUGPlacebo
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
Sponsors
National Institute on Drug Abuse (NIDA)
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
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.
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 25 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Days of Vaping Abstinence | Baseline-24 weeks | Those assigned to varenicline will have greater total number of days of vaping abstinence. Total number of days of vaping abstinence was assessed by self-report and verified by urine cotinine testing at each study visit. |
| Percentage of Participants With Continuous Nicotine Vaping Abstinence From Week 9 Through End of Follow-up (Week 24) | Weeks 9-24 | 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 on a timeline followback assessment and urinary cotinine \<50 ng/ml at each study visit in the designated timeframe. |
| Percentage of Change in Nicotine Product Exposure | Baseline-week 24 | Those assigned to varenicline will have greater percentage reduction in vaped nicotine product exposure than those assigned to placebo as determined by urine cotinine from baseline to week 24. Cotinine is a byproduct of nicotine that is used to measure exposure to nicotine product exposure. Positive values represent increases and negative values represent decreases. |
| Onset of Vaping Abstinence in Weeks | Baseline-24 weeks | Those assigned to varenicline will have earlier onset of abstinence. Onset of vaping abstinence (weeks) was assessed by participant self-report of vaping abstinence, and verified by urine cotinine testing. |
| Latency to First Lapse in Weeks | Baseline-24 weeks | Those assigned to varenicline will have longer latency to first lapse. This outcome was assessed via self-report and verified by urine cotinine testing. |
| Latency to Relapse in Weeks | Baseline-24 weeks | Those assigned to varenicline will have longer latency to relapse. This outcome was assessed by self-report and verified by urine cotinine testing at each study visit. |
| Duration of Vaping Abstinence in Weeks | Baseline-24 weeks | Those assigned to varenicline will have a longer duration of abstinence in weeks. This measure was assessed by self-report and verified by urine cotinine testing at each study visit. |
| Percentage of Participants With Continuous Nicotine Vaping Abstinence From Week 9 Through End of Treatment (Week 12) | Weeks 9-12 | 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 on a timeline followback assessment and urinary cotinine \<50 ng/mL at each study visit in the designated timeframe. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events During the Treatment Period | Baseline-week 12 | Adverse events are assessed via standardized questions prompting participants to report any changes in their physical or mental health. |
| Nicotine Withdrawal Symptoms: Mean Difference (Week 16 - Baseline) | Baseline to Week 16 | Symptoms will be assessed using the Minnesota Withdrawal Scale (MNWS), a 9-item self-rated scale of nicotine withdrawal symptoms, with scores ranging from 0 - 36, where higher scores indicate a greater degree of withdrawal. The difference between baseline and Week 16 will be computed for each participant. |
| Intensity of Nicotine Craving: Mean Difference (Week 12 - Baseline) | Baseline to week 12 | A Visual Analogue Scale was used to measure intensity of nicotine craving. The scale ranged from 0 (no desire at all) to 7 (unable to resist). Higher scores represent more intense nicotine craving. |
| Severity of Nicotine Craving: Mean Difference (Week 12 - Baseline) | Baseline to Week12 | Severity of nicotine cravings will be assessed using the Questionnaire of Vaping Craving (QVC), a 10-item measure of vaping craving, with scores ranging from 10 - 70, where higher scores indicate greater craving for vaping products. The difference between baseline and Week 12 will be computed for each participant. |
| Severity of Clinical Symptoms (Mood and Anxiety): Mean Difference (Week 16 - Baseline) | Baseline-week 16 | Severity of clinical symptoms will be assessed by the Mood and Anxiety Symptoms Questionnaire (MASQ-D30), a 30-item measure ranging from 30 - 150, with higher scores indicating a greater degree of clinical distress. The difference between baseline and Week 16 will be computed for each participant. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Amount of Substances Other Than Nicotine Consumed | Baseline-week 16 | 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. |
Countries
United States
Participant flow
Pre-assignment details
Five participants signed consent and were enrolled. One (1) subject was considered a screen fail and not randomized to an arm/group, and four (4) subjects were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Varenicline 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
Varenicline: 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 | 1 |
| Placebo 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
Placebo: 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 | 1 |
| Monitoring Only Participants will attend weekly and monthly sessions that will only consist of assessments. No study medication, no behavioral or texting support. | 2 |
| Total | 4 |
Baseline characteristics
| Characteristic | Varenicline | Placebo | Monitoring Only | Total |
|---|---|---|---|---|
| Age, Continuous | 21 years STANDARD_DEVIATION 0 | 21 years STANDARD_DEVIATION 0 | 21.5 years STANDARD_DEVIATION 0.5 | 21.25 years STANDARD_DEVIATION 0.43 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 | 0 / 2 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 2 / 2 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 | 2 / 2 |
Outcome results
Primary
Duration of Vaping Abstinence in Weeks
Those assigned to varenicline will have a longer duration of abstinence in weeks. This measure was assessed by self-report and verified by urine cotinine testing at each study visit.
Time frame: Baseline-24 weeks
Population: No participants in the monitoring group quit vaping.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Duration of Vaping Abstinence in Weeks | 15 Weeks |
| Placebo | Duration of Vaping Abstinence in Weeks | 22 Weeks |
Primary
Latency to First Lapse in Weeks
Those assigned to varenicline will have longer latency to first lapse. This outcome was assessed via self-report and verified by urine cotinine testing.
Time frame: Baseline-24 weeks
Population: No participants in the monitoring only group quit vaping, and as such, could not lapse.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Latency to First Lapse in Weeks | 10 Weeks |
| Placebo | Latency to First Lapse in Weeks | NA Weeks |
Primary
Latency to Relapse in Weeks
Those assigned to varenicline will have longer latency to relapse. This outcome was assessed by self-report and verified by urine cotinine testing at each study visit.
Time frame: Baseline-24 weeks
Population: No participants in the monitoring only group quit vaping, and as such, could not relapse.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Latency to Relapse in Weeks | NA Weeks |
| Placebo | Latency to Relapse in Weeks | NA Weeks |
Primary
Onset of Vaping Abstinence in Weeks
Those assigned to varenicline will have earlier onset of abstinence. Onset of vaping abstinence (weeks) was assessed by participant self-report of vaping abstinence, and verified by urine cotinine testing.
Time frame: Baseline-24 weeks
Population: No participants in the monitoring only group quit vaping.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Onset of Vaping Abstinence in Weeks | 8 Weeks |
| Placebo | Onset of Vaping Abstinence in Weeks | 2 Weeks |
Primary
Percentage of Change in Nicotine Product Exposure
Those assigned to varenicline will have greater percentage reduction in vaped nicotine product exposure than those assigned to placebo as determined by urine cotinine from baseline to week 24. Cotinine is a byproduct of nicotine that is used to measure exposure to nicotine product exposure. Positive values represent increases and negative values represent decreases.
Time frame: Baseline-week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | Percentage of Change in Nicotine Product Exposure | -99 percentage change in nicotine exposure |
| Placebo | Percentage of Change in Nicotine Product Exposure | -100 percentage change in nicotine exposure |
| Monitoring Only | Percentage of Change in Nicotine Product Exposure | 0 percentage change in nicotine exposure |
Primary
Percentage of Participants With Continuous Nicotine Vaping Abstinence From Week 9 Through End of Follow-up (Week 24)
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 on a timeline followback assessment and urinary cotinine \<50 ng/ml at each study visit in the designated timeframe.
Time frame: Weeks 9-24
Population: No participant reached 24 weeks in the study, and as such, were not included in the analysis.
Primary
Percentage of Participants With Continuous Nicotine Vaping Abstinence From Week 9 Through End of Treatment (Week 12)
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 on a timeline followback assessment and urinary cotinine \<50 ng/mL at each study visit in the designated timeframe.
Time frame: Weeks 9-12
Population: 5 people enrolled in the pilot, 1 was a screen fail, 4 were enrolled and have been included in the analysis. Due to the small number of participants enrolled in the pilot, data is presented as participant count.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varenicline | Percentage of Participants With Continuous Nicotine Vaping Abstinence From Week 9 Through End of Treatment (Week 12) | 0 Participants |
| Placebo | Percentage of Participants With Continuous Nicotine Vaping Abstinence From Week 9 Through End of Treatment (Week 12) | 1 Participants |
| Monitoring Only | Percentage of Participants With Continuous Nicotine Vaping Abstinence From Week 9 Through End of Treatment (Week 12) | 0 Participants |
Primary
Total Number of Days of Vaping Abstinence
Those assigned to varenicline will have greater total number of days of vaping abstinence. Total number of days of vaping abstinence was assessed by self-report and verified by urine cotinine testing at each study visit.
Time frame: Baseline-24 weeks
Population: No participant reached 24 weeks in the study, and as such, were not included in the analysis.
Secondary
Intensity of Nicotine Craving: Mean Difference (Week 12 - Baseline)
A Visual Analogue Scale was used to measure intensity of nicotine craving. The scale ranged from 0 (no desire at all) to 7 (unable to resist). Higher scores represent more intense nicotine craving.
Time frame: Baseline to week 12
Population: Measure data was not collected from any enrolled participant.
Secondary
Nicotine Withdrawal Symptoms: Mean Difference (Week 16 - Baseline)
Symptoms will be assessed using the Minnesota Withdrawal Scale (MNWS), a 9-item self-rated scale of nicotine withdrawal symptoms, with scores ranging from 0 - 36, where higher scores indicate a greater degree of withdrawal. The difference between baseline and Week 16 will be computed for each participant.
Time frame: Baseline to Week 16
Population: Participants in the placebo and monitoring group didn't provide post baseline outcome measure data, and therefore were not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Nicotine Withdrawal Symptoms: Mean Difference (Week 16 - Baseline) | -7 score on a scale | Standard Deviation 0 |
Secondary
Number of Adverse Events During the Treatment Period
Adverse events are assessed via standardized questions prompting participants to report any changes in their physical or mental health.
Time frame: Baseline-week 12
Population: Monitoring only participants didn't complete week 12, data includes AEs collected as of their last visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Number of Adverse Events During the Treatment Period | 3 Number of adverse events | Standard Deviation 0 |
| Placebo | Number of Adverse Events During the Treatment Period | 4 Number of adverse events | Standard Deviation 0 |
| Monitoring Only | Number of Adverse Events During the Treatment Period | 2.5 Number of adverse events | Standard Deviation 2.1 |
Secondary
Severity of Clinical Symptoms (Mood and Anxiety): Mean Difference (Week 16 - Baseline)
Severity of clinical symptoms will be assessed by the Mood and Anxiety Symptoms Questionnaire (MASQ-D30), a 30-item measure ranging from 30 - 150, with higher scores indicating a greater degree of clinical distress. The difference between baseline and Week 16 will be computed for each participant.
Time frame: Baseline-week 16
Population: participants in the monitoring group didn't provide post baseline outcome measure therefore were not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Severity of Clinical Symptoms (Mood and Anxiety): Mean Difference (Week 16 - Baseline) | -11 score on a scale | Standard Deviation 0 |
| Placebo | Severity of Clinical Symptoms (Mood and Anxiety): Mean Difference (Week 16 - Baseline) | -12 score on a scale | Standard Deviation 0 |
Secondary
Severity of Nicotine Craving: Mean Difference (Week 12 - Baseline)
Severity of nicotine cravings will be assessed using the Questionnaire of Vaping Craving (QVC), a 10-item measure of vaping craving, with scores ranging from 10 - 70, where higher scores indicate greater craving for vaping products. The difference between baseline and Week 12 will be computed for each participant.
Time frame: Baseline to Week12
Population: participants in the monitoring group didn't provide post baseline outcome measure therefore were not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Severity of Nicotine Craving: Mean Difference (Week 12 - Baseline) | -16 score on a scale | Standard Deviation 0 |
| Placebo | Severity of Nicotine Craving: Mean Difference (Week 12 - Baseline) | -18 score on a scale | Standard Deviation 0 |
Other Pre-specified
Amount of Substances Other Than Nicotine Consumed
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.
Time frame: Baseline-week 16