Nicotine Dependence, Vaping
Conditions
Keywords
Vaping, Nicotine, Adolescents, Cessation, Varenicline
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.
Interventions
DRUGDouble 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
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
BEHAVIORALQuitVaping
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.
BEHAVIORALThis 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.
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 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.
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
16 Years to 25 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Continuous 4-week Nicotine Vaping Abstinence at End of Treatment (Weeks 9-12) | Assessments at study weeks 9, 10, 11, and 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Continuous Nicotine Vaping Abstinence Over Study Weeks 9 to 24 | Study weeks 9, 10, 11, 12, 16, 20, 24 | 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 defined as observed point-prevalence abstinence over specified study visits at weeks 9, 10, 11, 12, 16, 20, and 24. Visits with self-reported abstinence missing bioverification were treated as missing, with missingness addressed via multiple imputation. |
| Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Study weeks 1-12 | Minnesota Nicotine Withdrawal Scale (MNWS) total scores over study weeks 1 to 12. The MNWS is an 8-item measure assessing the severity of nicotine withdrawal symptoms. Items are scored on an ordinal scale from 0 (not at all) to 4 (extreme) with total scores ranging from 0 to 32. Higher scores indicate greater severity of nicotine withdrawal symptoms. Missingness due to missed visits and/or dropout was addressed via multiple imputation. |
| Seven-Day Point-Prevalence Nicotine Vaping Abstinence at End of Treatment (Week 12) | Study week 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. Visits with self-reported abstinence missing bioverification were treated as missing, with missingness addressed via multiple imputation. |
| Mood and Anxiety Symptoms Questionnaire (MASQ-D30) General Distress Subscore (Weeks 4, 8, and 12) | Study weeks 4, 8, 12 | Summed scores from the General Distress Subscale of the 30-Item Mood and Anxiety Symptoms Questionnaire (MASQ-D30) over Study Weeks 4,8, and 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. Missingness due to missed visits and/or dropout was addressed with multiple imputation. |
| Neuropsychiatric Adverse Event Inventory (NAEI) Elicited Adverse Events by Week 12 | Study weeks 1-12 | The Neuropsychiatric Adverse Event Inventory (NAEI) is a structured interview used to assess neuropsychiatric adverse events. This outcome reports on the number of participants who reported at least one adverse event on the NAEI between the first study week (Week 1) to the end of treatment (Week 12). |
| Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Study weeks 1-12 | 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. Missingness due to missed visits and/or dropout are addressed with multiple imputation. |
Countries
United States
Participant flow
Recruitment details
This trial recruited participants from a single U.S. state from June 2022 to November 2023.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 88 |
| 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. | 87 |
| 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. | 86 |
| Total | 261 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Study Follow Up (Week 24) | Lost to Follow-up | 0 | 1 | 0 |
| Study Follow Up (Week 24) | Withdrawal by Subject | 0 | 1 | 0 |
| Study Intervention (Week 12) | Lost to Follow-up | 0 | 2 | 1 |
| Study Intervention (Week 12) | Withdrawal by Subject | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Double Blind Varenicline (V+BC) | Single Blind Enhanced Usual Care (EUC) | Double Blind Placebo (P+BC) |
|---|---|---|---|---|
| Age, Continuous | 21.5 years STANDARD_DEVIATION 2 | 21.6 years STANDARD_DEVIATION 2 | 21.4 years STANDARD_DEVIATION 2 | 21.4 years STANDARD_DEVIATION 2.1 |
| Alcohol: Median number of days used per week in last 30 days | 1.2 days per week | 1.4 days per week | 0.9 days per week | 1.2 days per week |
| Alcohol: Past 30-day use | 248 Participants | 87 Participants | 82 Participants | 79 Participants |
| Alcohol Use Disorders Identification Test (AUDIT) | 6 score on a scale | 5 score on a scale | 6 score on a scale | 7 score on a scale |
| Any self-reported psychiatric diagnosis | 176 Participants | 60 Participants | 55 Participants | 61 Participants |
| Cannabis: Median number of days used per week in last 30 days | 1.4 days per week | 0.9 days per week | 1.2 days per week | 2.1 days per week |
| Cannabis: Past 30-day use | 187 Participants | 61 Participants | 62 Participants | 64 Participants |
| Cannabis Use Disorders Identification Test- Revised (CUDIT-R) | 7 score on a scale | 6 score on a scale | 8 score on a scale | 8 score on a scale |
| Combusted Tobacco: Median number of days used per week in last 30 days | 0 days per week | 0 days per week | 0 days per week | 0 days per week |
| Combusted Tobacco: Past 30-day use | 21 Participants | 6 Participants | 8 Participants | 7 Participants |
| Current Psychotropic Medication Use | 99 Participants | 33 Participants | 33 Participants | 33 Participants |
| E-Cigarette Dependence Inventory (ECDI) | 13.0 total score on a scale STANDARD_DEVIATION 3.9 | 12.5 total score on a scale STANDARD_DEVIATION 3.8 | 12.8 total score on a scale STANDARD_DEVIATION 3.8 | 13.7 total score on a scale STANDARD_DEVIATION 4 |
| E-cigarette use: Median number of days used per week in last 30 days | 7 days per week | 7 days per week | 7 days per week | 7 days per week |
| Ethnicity (NIH/OMB) Hispanic or Latino | 43 Participants | 17 Participants | 8 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 218 Participants | 71 Participants | 78 Participants | 69 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Lifetime cigarettes smoked ≥100 | 21 Participants | 9 Participants | 5 Participants | 7 Participants |
| Minnesota Nicotine Withdrawal Scale (MNWS) | 10.8 score on a scale STANDARD_DEVIATION 6 | 10.5 score on a scale STANDARD_DEVIATION 6.1 | 11.2 score on a scale STANDARD_DEVIATION 6 | 10.6 score on a scale STANDARD_DEVIATION 6.1 |
| Mood and Anxiety Symptoms Questionnaire (MASQ-D30): General Distress Score | 17.9 score on a scale STANDARD_DEVIATION 6.9 | 17.4 score on a scale STANDARD_DEVIATION 6.7 | 18.8 score on a scale STANDARD_DEVIATION 7.9 | 17.5 score on a scale STANDARD_DEVIATION 6 |
| Mood and Anxiety Symptoms Questionnaire (MASQ-D30) Total Score | 58.2 score on a scale STANDARD_DEVIATION 14.8 | 57.8 score on a scale STANDARD_DEVIATION 14.5 | 58.6 score on a scale STANDARD_DEVIATION 15.3 | 58.3 score on a scale STANDARD_DEVIATION 14.8 |
| Motivation to Quit Vaping | 7.0 score on a scale STANDARD_DEVIATION 1.7 | 7.1 score on a scale STANDARD_DEVIATION 1.7 | 7.1 score on a scale STANDARD_DEVIATION 1.6 | 6.7 score on a scale STANDARD_DEVIATION 1.8 |
| Post-secondary School | 257 Participants | 86 Participants | 86 Participants | 85 Participants |
| Questionnaire of Vaping Craving (QVC) | 40.7 score on a scale STANDARD_DEVIATION 12.9 | 41.3 score on a scale STANDARD_DEVIATION 11.5 | 38.5 score on a scale STANDARD_DEVIATION 13.8 | 42.3 score on a scale STANDARD_DEVIATION 13.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 48 Participants | 13 Participants | 18 Participants | 17 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 5 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 28 Participants | 10 Participants | 8 Participants | 10 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 | 8 Participants | 4 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 160 Participants | 56 Participants | 55 Participants | 49 Participants |
| Region of Enrollment United States | 261 participants | 88 participants | 86 participants | 87 participants |
| Sex: Female, Male Female | 139 Participants | 46 Participants | 46 Participants | 47 Participants |
| Sex: Female, Male Male | 122 Participants | 42 Participants | 40 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 88 | 0 / 86 | 0 / 86 |
| other Total, other adverse events | 78 / 88 | 73 / 86 | 69 / 86 |
| serious Total, serious adverse events | 1 / 88 | 3 / 86 | 1 / 86 |
Outcome results
Primary
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.
Time frame: Assessments at study weeks 9, 10, 11, and 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double Blind Varenicline (V+BC) | Continuous 4-week Nicotine Vaping Abstinence at End of Treatment (Weeks 9-12) | 45 Participants |
| Double Blind Placebo (P+BC) | Continuous 4-week Nicotine Vaping Abstinence at End of Treatment (Weeks 9-12) | 12 Participants |
| Single Blind Enhanced Usual Care (EUC) | Continuous 4-week Nicotine Vaping Abstinence at End of Treatment (Weeks 9-12) | 5 Participants |
p-value: <0.001Regression, Logistic
p-value: <0.00195% CI: [3, 14.1]Regression, Logistic
Secondary
Continuous Nicotine Vaping Abstinence Over Study Weeks 9 to 24
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 defined as observed point-prevalence abstinence over specified study visits at weeks 9, 10, 11, 12, 16, 20, and 24. Visits with self-reported abstinence missing bioverification were treated as missing, with missingness addressed via multiple imputation.
Time frame: Study weeks 9, 10, 11, 12, 16, 20, 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double Blind Varenicline (V+BC) | Continuous Nicotine Vaping Abstinence Over Study Weeks 9 to 24 | 25 Participants |
| Double Blind Placebo (P+BC) | Continuous Nicotine Vaping Abstinence Over Study Weeks 9 to 24 | 6 Participants |
| Single Blind Enhanced Usual Care (EUC) | Continuous Nicotine Vaping Abstinence Over Study Weeks 9 to 24 | 3 Participants |
p-value: 0.00195% CI: [2.1, 16.9]Regression, Logistic
p-value: <0.001Regression, Logistic
Secondary
Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12)
Minnesota Nicotine Withdrawal Scale (MNWS) total scores over study weeks 1 to 12. The MNWS is an 8-item measure assessing the severity of nicotine withdrawal symptoms. Items are scored on an ordinal scale from 0 (not at all) to 4 (extreme) with total scores ranging from 0 to 32. Higher scores indicate greater severity of nicotine withdrawal symptoms. Missingness due to missed visits and/or dropout was addressed via multiple imputation.
Time frame: Study weeks 1-12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double Blind Varenicline (V+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 4 | 7.2 score on a scale | Standard Deviation 5.7 |
| Double Blind Varenicline (V+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 7 | 6.3 score on a scale | Standard Deviation 6 |
| Double Blind Varenicline (V+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 9 | 5.4 score on a scale | Standard Deviation 5 |
| Double Blind Varenicline (V+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 10 | 5.1 score on a scale | Standard Deviation 5.2 |
| Double Blind Varenicline (V+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 12 | 4.5 score on a scale | Standard Deviation 4.5 |
| Double Blind Varenicline (V+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 5 | 7.1 score on a scale | Standard Deviation 6 |
| Double Blind Varenicline (V+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 11 | 4.6 score on a scale | Standard Deviation 5 |
| Double Blind Varenicline (V+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 1 | 8.7 score on a scale | Standard Deviation 6.2 |
| Double Blind Varenicline (V+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 6 | 6.8 score on a scale | Standard Deviation 6 |
| Double Blind Varenicline (V+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 2 | 9.2 score on a scale | Standard Deviation 6.3 |
| Double Blind Varenicline (V+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 3 | 8.2 score on a scale | Standard Deviation 6.4 |
| Double Blind Varenicline (V+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 8 | 6.2 score on a scale | Standard Deviation 5.6 |
| Double Blind Placebo (P+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 3 | 10.5 score on a scale | Standard Deviation 5.8 |
| Double Blind Placebo (P+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 5 | 9.2 score on a scale | Standard Deviation 6.3 |
| Double Blind Placebo (P+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 2 | 10.6 score on a scale | Standard Deviation 6 |
| Double Blind Placebo (P+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 7 | 8.5 score on a scale | Standard Deviation 5.8 |
| Double Blind Placebo (P+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 6 | 8.2 score on a scale | Standard Deviation 5.8 |
| Double Blind Placebo (P+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 8 | 7.9 score on a scale | Standard Deviation 5.8 |
| Double Blind Placebo (P+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 9 | 7.6 score on a scale | Standard Deviation 5.5 |
| Double Blind Placebo (P+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 11 | 6.6 score on a scale | Standard Deviation 5.2 |
| Double Blind Placebo (P+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 1 | 10.6 score on a scale | Standard Deviation 5.8 |
| Double Blind Placebo (P+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 4 | 10.9 score on a scale | Standard Deviation 6.2 |
| Double Blind Placebo (P+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 12 | 7.0 score on a scale | Standard Deviation 6.4 |
| Double Blind Placebo (P+BC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 10 | 6.8 score on a scale | Standard Deviation 5.3 |
| Single Blind Enhanced Usual Care (EUC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 12 | 7.6 score on a scale | Standard Deviation 5.5 |
| Single Blind Enhanced Usual Care (EUC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 5 | 8.8 score on a scale | Standard Deviation 5.9 |
| Single Blind Enhanced Usual Care (EUC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 8 | 7.3 score on a scale | Standard Deviation 5.8 |
| Single Blind Enhanced Usual Care (EUC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 10 | 7.9 score on a scale | Standard Deviation 5.9 |
| Single Blind Enhanced Usual Care (EUC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 1 | 10.4 score on a scale | Standard Deviation 5.8 |
| Single Blind Enhanced Usual Care (EUC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 2 | 10.0 score on a scale | Standard Deviation 5.9 |
| Single Blind Enhanced Usual Care (EUC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 3 | 9.5 score on a scale | Standard Deviation 5.8 |
| Single Blind Enhanced Usual Care (EUC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 6 | 8.1 score on a scale | Standard Deviation 6 |
| Single Blind Enhanced Usual Care (EUC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 7 | 7.7 score on a scale | Standard Deviation 5.3 |
| Single Blind Enhanced Usual Care (EUC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 9 | 8.1 score on a scale | Standard Deviation 6.1 |
| Single Blind Enhanced Usual Care (EUC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 11 | 7.7 score on a scale | Standard Deviation 5.5 |
| Single Blind Enhanced Usual Care (EUC) | Minnesota Nicotine Withdrawal Scale (MNWS) Total Score (Weeks 1-12) | Week 4 | 9.3 score on a scale | Standard Deviation 5.6 |
p-value: 0.00195% CI: [-2.93, -0.83]Regression, Linear
p-value: <0.001Regression, Linear
Secondary
Mood and Anxiety Symptoms Questionnaire (MASQ-D30) General Distress Subscore (Weeks 4, 8, and 12)
Summed scores from the General Distress Subscale of the 30-Item Mood and Anxiety Symptoms Questionnaire (MASQ-D30) over Study Weeks 4,8, and 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. Missingness due to missed visits and/or dropout was addressed with multiple imputation.
Time frame: Study weeks 4, 8, 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double Blind Varenicline (V+BC) | Mood and Anxiety Symptoms Questionnaire (MASQ-D30) General Distress Subscore (Weeks 4, 8, and 12) | Week 8 | 15.6 score on a scale | Standard Deviation 6.3 |
| Double Blind Varenicline (V+BC) | Mood and Anxiety Symptoms Questionnaire (MASQ-D30) General Distress Subscore (Weeks 4, 8, and 12) | Week 4 | 15.8 score on a scale | Standard Deviation 5.8 |
| Double Blind Varenicline (V+BC) | Mood and Anxiety Symptoms Questionnaire (MASQ-D30) General Distress Subscore (Weeks 4, 8, and 12) | Week 12 | 15.2 score on a scale | Standard Deviation 5.8 |
| Double Blind Placebo (P+BC) | Mood and Anxiety Symptoms Questionnaire (MASQ-D30) General Distress Subscore (Weeks 4, 8, and 12) | Week 8 | 16.9 score on a scale | Standard Deviation 6.2 |
| Double Blind Placebo (P+BC) | Mood and Anxiety Symptoms Questionnaire (MASQ-D30) General Distress Subscore (Weeks 4, 8, and 12) | Week 4 | 19 score on a scale | Standard Deviation 6.5 |
| Double Blind Placebo (P+BC) | Mood and Anxiety Symptoms Questionnaire (MASQ-D30) General Distress Subscore (Weeks 4, 8, and 12) | Week 12 | 16.6 score on a scale | Standard Deviation 6.3 |
| Single Blind Enhanced Usual Care (EUC) | Mood and Anxiety Symptoms Questionnaire (MASQ-D30) General Distress Subscore (Weeks 4, 8, and 12) | Week 4 | 17.9 score on a scale | Standard Deviation 6.6 |
| Single Blind Enhanced Usual Care (EUC) | Mood and Anxiety Symptoms Questionnaire (MASQ-D30) General Distress Subscore (Weeks 4, 8, and 12) | Week 12 | 17 score on a scale | Standard Deviation 6.9 |
| Single Blind Enhanced Usual Care (EUC) | Mood and Anxiety Symptoms Questionnaire (MASQ-D30) General Distress Subscore (Weeks 4, 8, and 12) | Week 8 | 16.9 score on a scale | Standard Deviation 6.2 |
p-value: 0.00895% CI: [-3.08, -0.48]Regression, Linear
p-value: 0.02Regression, Linear
Secondary
Neuropsychiatric Adverse Event Inventory (NAEI) Elicited Adverse Events by Week 12
The Neuropsychiatric Adverse Event Inventory (NAEI) is a structured interview used to assess neuropsychiatric adverse events. This outcome reports on the number of participants who reported at least one adverse event on the NAEI between the first study week (Week 1) to the end of treatment (Week 12).
Time frame: Study weeks 1-12
Population: Analysis limited to participants who received randomized treatment. Because one participant randomized to placebo (P+BC) did not receive treatment, the denominator for the analysis is 86.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double Blind Varenicline (V+BC) | Neuropsychiatric Adverse Event Inventory (NAEI) Elicited Adverse Events by Week 12 | 71 Participants |
| Double Blind Placebo (P+BC) | Neuropsychiatric Adverse Event Inventory (NAEI) Elicited Adverse Events by Week 12 | 61 Participants |
| Single Blind Enhanced Usual Care (EUC) | Neuropsychiatric Adverse Event Inventory (NAEI) Elicited Adverse Events by Week 12 | 78 Participants |
p-value: 0.16Fisher Exact
p-value: 0.083Fisher Exact
Secondary
Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12)
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. Missingness due to missed visits and/or dropout are addressed with multiple imputation.
Time frame: Study weeks 1-12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double Blind Varenicline (V+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 8 | 17.8 score on a scale | Standard Deviation 9.8 |
| Double Blind Varenicline (V+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 2 | 29 score on a scale | Standard Deviation 12.2 |
| Double Blind Varenicline (V+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 9 | 17.1 score on a scale | Standard Deviation 9.7 |
| Double Blind Varenicline (V+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 11 | 16 score on a scale | Standard Deviation 8.7 |
| Double Blind Varenicline (V+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 3 | 25.8 score on a scale | Standard Deviation 12.9 |
| Double Blind Varenicline (V+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 12 | 14.4 score on a scale | Standard Deviation 6.9 |
| Double Blind Varenicline (V+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 10 | 15.9 score on a scale | Standard Deviation 8.7 |
| Double Blind Varenicline (V+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 4 | 22.8 score on a scale | Standard Deviation 11.4 |
| Double Blind Varenicline (V+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 5 | 20.4 score on a scale | Standard Deviation 10.1 |
| Double Blind Varenicline (V+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 1 | 34.1 score on a scale | Standard Deviation 12.1 |
| Double Blind Varenicline (V+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 6 | 19.3 score on a scale | Standard Deviation 10.5 |
| Double Blind Varenicline (V+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 7 | 18.9 score on a scale | Standard Deviation 10.3 |
| Double Blind Placebo (P+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 7 | 27.8 score on a scale | Standard Deviation 14 |
| Double Blind Placebo (P+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 6 | 29.2 score on a scale | Standard Deviation 13.1 |
| Double Blind Placebo (P+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 4 | 33.2 score on a scale | Standard Deviation 13.4 |
| Double Blind Placebo (P+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 9 | 25.4 score on a scale | Standard Deviation 13.1 |
| Double Blind Placebo (P+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 2 | 37.3 score on a scale | Standard Deviation 13 |
| Double Blind Placebo (P+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 10 | 24 score on a scale | Standard Deviation 12.2 |
| Double Blind Placebo (P+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 1 | 39 score on a scale | Standard Deviation 12.2 |
| Double Blind Placebo (P+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 11 | 22.1 score on a scale | Standard Deviation 11.5 |
| Double Blind Placebo (P+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 5 | 32.2 score on a scale | Standard Deviation 12.8 |
| Double Blind Placebo (P+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 8 | 26.9 score on a scale | Standard Deviation 13.6 |
| Double Blind Placebo (P+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 12 | 22 score on a scale | Standard Deviation 11.2 |
| Double Blind Placebo (P+BC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 3 | 34.8 score on a scale | Standard Deviation 12.1 |
| Single Blind Enhanced Usual Care (EUC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 12 | 28.1 score on a scale | Standard Deviation 13.3 |
| Single Blind Enhanced Usual Care (EUC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 10 | 30.4 score on a scale | Standard Deviation 13.3 |
| Single Blind Enhanced Usual Care (EUC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 1 | 37 score on a scale | Standard Deviation 13 |
| Single Blind Enhanced Usual Care (EUC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 3 | 34.1 score on a scale | Standard Deviation 12.3 |
| Single Blind Enhanced Usual Care (EUC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 4 | 34.1 score on a scale | Standard Deviation 13.4 |
| Single Blind Enhanced Usual Care (EUC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 5 | 32 score on a scale | Standard Deviation 13.8 |
| Single Blind Enhanced Usual Care (EUC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 6 | 32.5 score on a scale | Standard Deviation 14 |
| Single Blind Enhanced Usual Care (EUC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 7 | 31.2 score on a scale | Standard Deviation 14.4 |
| Single Blind Enhanced Usual Care (EUC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 8 | 30 score on a scale | Standard Deviation 14.8 |
| Single Blind Enhanced Usual Care (EUC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 9 | 31.2 score on a scale | Standard Deviation 13 |
| Single Blind Enhanced Usual Care (EUC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 11 | 28.9 score on a scale | Standard Deviation 14.1 |
| Single Blind Enhanced Usual Care (EUC) | Questionnaire of Vaping Craving (QVC) Total Scores (Weeks 1-12) | Week 2 | 36.6 score on a scale | Standard Deviation 12.8 |
p-value: <0.00195% CI: [-9.08, -4.45]Regression, Linear
p-value: <0.001Regression, Linear
Secondary
Seven-Day Point-Prevalence Nicotine Vaping Abstinence at End of Treatment (Week 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. Visits with self-reported abstinence missing bioverification were treated as missing, with missingness addressed via multiple imputation.
Time frame: Study week 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double Blind Varenicline (V+BC) | Seven-Day Point-Prevalence Nicotine Vaping Abstinence at End of Treatment (Week 12) | 60 Participants |
| Double Blind Placebo (P+BC) | Seven-Day Point-Prevalence Nicotine Vaping Abstinence at End of Treatment (Week 12) | 22 Participants |
| Single Blind Enhanced Usual Care (EUC) | Seven-Day Point-Prevalence Nicotine Vaping Abstinence at End of Treatment (Week 12) | 13 Participants |
p-value: <0.00195% CI: [3.1, 12.3]Regression, Logistic
p-value: <0.001Regression, Logistic