EVAR: Combination of E-cigarettes and Varenicline for Tobacco Harm Reduction
Study Details
Study Description
Brief Summary
This open-label study will explore the impact of varenicline on the process of switching from combustible cigarettes (CC) to an e-cigarette. Varenicline is currently the most efficacious single pharmacotherapy for smoking cessation, and through its actions as an agonist or partial agonist at various nicotinic acetylcholine receptor subtypes, serves to diminish the rewarding effects of cigarette smoking. Diminishing the rewarding effects of smoking might facilitate the transition from CC to e-cigarettes. On the other hand, varenicline might attenuate the rewarding effects of nicotine-containing e-cigarettes as well, which could hamper the transition. Thus, the study will provide important information about the actions of varenicline on CC as well as e-cigarettes. There is no therapeutic intent in that smokers' nicotine/tobacco dependence will not be treated; the goal is to switch from one form of nicotine/tobacco dependence (CC) to dependence on a different tobacco product (e-cigarettes).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Varenicline plus e-cigarette Participants enrolled in the study will receive a G6 e-cigarette at V2 for ad libitum use. The FDA approved starter kit of varenicline will be provided to participants at V3 (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7) along with additional G6 cartomizers. After the first week of varenicline, participants will receive the FDA-approved standard dose of varenicline (1 mg twice daily) and will continue to receive enough G6 cartomizers for the next 11 weeks. |
Drug: Varenicline
0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7; then 1 mg twice daily for the remaining 11 weeks.
Other Names:
Other: e-cigarette
Each G6 prefilled cartomizer contains a 50/50 blend nicotine salt with 35mg nicotine strength.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participant Reporting Continuous Complete Switching From Cigarettes to Halo G6 [Weeks 8-11]
The primary switching outcome will be smoking abstinence during weeks 8-11 post-switching date. Complete switching from combustible cigarette use at each time point will be defined by a self-report of no cigarette smoking (not even a puff) since the prior session.
- Number of Participants Confirmed (by Expired Air CO) to Have Switched From Cigarettes to Halo G6 [Weeks 8-11]
The primary switching outcome will be smoking abstinence during weeks 8-11 post-switching date. Complete switching from combustible cigarette use at each time point confirmed by an expired air CO reading of less than 5 ppm.
Secondary Outcome Measures
- Number of Participants Reporting Point Abstinence From Smoking Cigarettes at 6 Months Post-Switch [6 months]
Point abstinence will be defined by a self-report of no cigarette smoking (not even a puff) in the last seven days at six months post-switch.
Other Outcome Measures
- Mean Changes in Arterial Flow When Smokers Switch From Cigarettes to E-cigarettes [Baseline (Visit 1) and 13 weeks (Visit 7)]
Ankle-Brachial Index (ABI) use to evaluate vascular changes when smokers change from cigarettes to e-cigarettes over a 13-week period. Measurements will be obtained using a manual sphygmomanometer and an 8- to 10- MHz doppler ultrasound probe. Subjects will undergo this testing at Visit 1 (baseline data) and at the end of study (Visit 7). Ankle Brachial Index (ABI) is the ratio of the blood pressure in the lower legs to the blood pressure in the arms. The normal range for the ankle-brachial index is between 0.90 and 1.30. An index of 0.41 to 0.90 indicates mild to moderate arterial disease and an index of 0.40 and lower indicates severe disease
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Has signed the ICF and is able to read and understand the information provided in the consent form.
-
Is 21 to 65 years of age (inclusive) at screening.
-
Smokes at least 10 commercially available cigarettes per day (no brand restrictions), for the last 12 months.
-
Has an expired air carbon monoxide reading of at least 10 ppm at screening.
-
Interested in switching to an electronic cigarette.
-
Willing and able to comply with the requirements of the study.
-
Owns a smart phone with text message and data capabilities compatible with necessary surveys.
Exclusion Criteria:
-
Is unhealthy or cannot participate in the study for any reason (e.g., medical, psychiatric, and/or social reason) as judged by the Investigator or designated medical staff based on all available assessments from the screening period (e.g., safety laboratory, vital signs, physical examination, Ankle-Brachial Index, ECG, concomitant medications and medical history).
-
PHQ-9 score greater than 9, or a score greater than 0 on item #9 ("Thoughts that you would be better off dead, or of hurting yourself in some way") at screening.
-
Planned use of an FDA-approved smoking cessation product during the study.
-
High blood pressure (systolic > 150 mmHg or diastolic >95 mmHg) at screening.
-
Body mass index (BMI) less than 15.0 kg/m2 or greater than 40.0 kg/m2.
-
Coronary heart disease, structural cardiac disease (including, but not limited to valvular heart disease or cardiac murmurs), cardiac dysrhythmias, syncope, cardiac chest pain, or history of heart attack or heart failure.
-
Has received psychotherapy or behavioral treatments potentially impacting symptoms of depression, anxiety, or nicotine withdrawal within 30 days of screening, or during the study.
-
Taking antidepressants, psychoactive medications (e.g. antipsychotics, benzodiazepines, hypnotics) or medications that prolong QTc.
-
Use of any of these products in the past 30 days: a. Illegal drugs (or if the urine drug screen is positive for cocaine, THC, amphetamines, methamphetamines, or opiates);
- Experimental (investigational) drugs that are unknown to subject; c. Chronic opiate use.
-
Use of smokeless tobacco (chewing tobacco, snuff), cigars (except for "Black & Mild" cigars or Cigarillos), pipes, hookah, e-cigarettes, nicotine replacement therapy or other smoking cessation treatments within 14 days of screening.
-
Pregnant or nursing (by self-report) or has a positive pregnancy test.
-
Enrollment requirements met.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Rose Research Center | Charlotte | North Carolina | United States | 28262 |
| 2 | Rose Research Center | Raleigh | North Carolina | United States | 27617 |
Sponsors and Collaborators
- Rose Research Center, LLC
- Foundation for a Smoke-Free World
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- EVAR
Study Results
Participant Flow
| Recruitment Details | The study was conducted in both the Raleigh, NC and Charlotte, NC offices of Rose Research Center. Enrollment started on 19 Nov 2019 and ended on 08 Jul 2020. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Varenicline Plus E-cigarette |
|---|---|
| Arm/Group Description | Participants enrolled in the study will receive a G6 e-cigarette at V2 for ad libitum use. The FDA approved starter kit of varenicline will be provided to participants at V3 (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7) along with additional G6 cartomizers. After the first week of varenicline, participants will receive the FDA-approved standard dose of varenicline (1 mg twice daily) and will continue to receive enough G6 cartomizers for the next 11 weeks. Varenicline: 0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7; then 1 mg twice daily for the remaining 11 weeks. e-cigarette: Each G6 prefilled cartomizer contains a 50/50 blend nicotine salt with 35mg nicotine strength. |
| Period Title: Overall Study | |
| STARTED | 25 |
| COMPLETED | 23 |
| NOT COMPLETED | 2 |
Baseline Characteristics
| Arm/Group Title | Varenicline Plus E-cigarette |
|---|---|
| Arm/Group Description | Participants enrolled in the study will receive a G6 e-cigarette at V2 for ad libitum use. The FDA approved starter kit of varenicline will be provided to participants at V3 (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7) along with additional G6 cartomizers. After the first week of varenicline, participants will receive the FDA-approved standard dose of varenicline (1 mg twice daily) and will continue to receive enough G6 cartomizers for the next 11 weeks. Varenicline: 0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7; then 1 mg twice daily for the remaining 11 weeks. e-cigarette: Each G6 prefilled cartomizer contains a 50/50 blend nicotine salt with 35mg nicotine strength. |
| Overall Participants | 25 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
46.92
(9.10)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
13
52%
|
| Male |
12
48%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
2
8%
|
| Not Hispanic or Latino |
23
92%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
6
24%
|
| White |
19
76%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
25
100%
|
Outcome Measures
| Title | Number of Participant Reporting Continuous Complete Switching From Cigarettes to Halo G6 |
|---|---|
| Description | The primary switching outcome will be smoking abstinence during weeks 8-11 post-switching date. Complete switching from combustible cigarette use at each time point will be defined by a self-report of no cigarette smoking (not even a puff) since the prior session. |
| Time Frame | Weeks 8-11 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Varenicline Plus E-cigarette |
|---|---|
| Arm/Group Description | Participants enrolled in the study will receive a G6 e-cigarette at V2 for ad libitum use. The FDA approved starter kit of varenicline will be provided to participants at V3 (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7) along with additional G6 cartomizers. After the first week of varenicline, participants will receive the FDA-approved standard dose of varenicline (1 mg twice daily) and will continue to receive enough G6 cartomizers for the next 11 weeks. Varenicline: 0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7; then 1 mg twice daily for the remaining 11 weeks. e-cigarette: Each G6 prefilled cartomizer contains a 50/50 blend nicotine salt with 35mg nicotine strength. |
| Measure Participants | 25 |
| Count of Participants [Participants] |
8
32%
|
| Title | Number of Participants Confirmed (by Expired Air CO) to Have Switched From Cigarettes to Halo G6 |
|---|---|
| Description | The primary switching outcome will be smoking abstinence during weeks 8-11 post-switching date. Complete switching from combustible cigarette use at each time point confirmed by an expired air CO reading of less than 5 ppm. |
| Time Frame | Weeks 8-11 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Varenicline Plus E-cigarette |
|---|---|
| Arm/Group Description | Participants enrolled in the study will receive a G6 e-cigarette at V2 for ad libitum use. The FDA approved starter kit of varenicline will be provided to participants at V3 (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7) along with additional G6 cartomizers. After the first week of varenicline, participants will receive the FDA-approved standard dose of varenicline (1 mg twice daily) and will continue to receive enough G6 cartomizers for the next 11 weeks. Varenicline: 0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7; then 1 mg twice daily for the remaining 11 weeks. e-cigarette: Each G6 prefilled cartomizer contains a 50/50 blend nicotine salt with 35mg nicotine strength. |
| Measure Participants | 25 |
| Count of Participants [Participants] |
8
32%
|
| Title | Number of Participants Reporting Point Abstinence From Smoking Cigarettes at 6 Months Post-Switch |
|---|---|
| Description | Point abstinence will be defined by a self-report of no cigarette smoking (not even a puff) in the last seven days at six months post-switch. |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Varenicline Plus E-cigarette |
|---|---|
| Arm/Group Description | Participants enrolled in the study will receive a G6 e-cigarette at V2 for ad libitum use. The FDA approved starter kit of varenicline will be provided to participants at V3 (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7) along with additional G6 cartomizers. After the first week of varenicline, participants will receive the FDA-approved standard dose of varenicline (1 mg twice daily) and will continue to receive enough G6 cartomizers for the next 11 weeks. Varenicline: 0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7; then 1 mg twice daily for the remaining 11 weeks. e-cigarette: Each G6 prefilled cartomizer contains a 50/50 blend nicotine salt with 35mg nicotine strength. |
| Measure Participants | 25 |
| Count of Participants [Participants] |
16
64%
|
| Title | Mean Changes in Arterial Flow When Smokers Switch From Cigarettes to E-cigarettes |
|---|---|
| Description | Ankle-Brachial Index (ABI) use to evaluate vascular changes when smokers change from cigarettes to e-cigarettes over a 13-week period. Measurements will be obtained using a manual sphygmomanometer and an 8- to 10- MHz doppler ultrasound probe. Subjects will undergo this testing at Visit 1 (baseline data) and at the end of study (Visit 7). Ankle Brachial Index (ABI) is the ratio of the blood pressure in the lower legs to the blood pressure in the arms. The normal range for the ankle-brachial index is between 0.90 and 1.30. An index of 0.41 to 0.90 indicates mild to moderate arterial disease and an index of 0.40 and lower indicates severe disease |
| Time Frame | Baseline (Visit 1) and 13 weeks (Visit 7) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 10 participants were not able to come to the lab for ABI evaluation at Visit 7 because of COVID restrictions. |
| Arm/Group Title | Varenicline Plus E-cigarette |
|---|---|
| Arm/Group Description | Participants enrolled in the study will receive a G6 e-cigarette at V2 for ad libitum use. The FDA approved starter kit of varenicline will be provided to participants at V3 (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7) along with additional G6 cartomizers. After the first week of varenicline, participants will receive the FDA-approved standard dose of varenicline (1 mg twice daily) and will continue to receive enough G6 cartomizers for the next 11 weeks. Varenicline: 0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7; then 1 mg twice daily for the remaining 11 weeks. e-cigarette: Each G6 prefilled cartomizer contains a 50/50 blend nicotine salt with 35mg nicotine strength. |
| Measure Participants | 13 |
| Mean (Standard Deviation) [ratio] |
-0.05
(0.12)
|
Adverse Events
| Time Frame | Data were collected during the 13 week study period. | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Varenicline Plus E-cigarette | |
| Arm/Group Description | Participants enrolled in the study will receive a G6 e-cigarette at V2 for ad libitum use. The FDA approved starter kit of varenicline will be provided to participants at V3 (0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7) along with additional G6 cartomizers. After the first week of varenicline, participants will receive the FDA-approved standard dose of varenicline (1 mg twice daily) and will continue to receive enough G6 cartomizers for the next 11 weeks. Varenicline: 0.5 mg nightly for days 1-3, then 0.5 mg twice daily for days 4-7; then 1 mg twice daily for the remaining 11 weeks. e-cigarette: Each G6 prefilled cartomizer contains a 50/50 blend nicotine salt with 35mg nicotine strength. | |
All Cause Mortality |
||
| Varenicline Plus E-cigarette | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/25 (0%) | |
Serious Adverse Events |
||
| Varenicline Plus E-cigarette | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/25 (4%) | |
| Musculoskeletal and connective tissue disorders | ||
| Allergic Reaction to lidocaine | 1/25 (4%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Varenicline Plus E-cigarette | ||
| Affected / at Risk (%) | # Events | |
| Total | 22/25 (88%) | |
| Gastrointestinal disorders | ||
| Vomiting | 2/25 (8%) | 3 |
| Nausea | 10/25 (40%) | 10 |
| Constipation | 2/25 (8%) | 2 |
| Nervous system disorders | ||
| Headache | 6/25 (24%) | 6 |
| Insomnia | 4/25 (16%) | 5 |
| Nightmares/ Vivid Dreams | 3/25 (12%) | 3 |
| Psychiatric disorders | ||
| Agitation/Anxiety | 2/25 (8%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 5/25 (20%) | 5 |
| Sore Throat | 2/25 (8%) | 2 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Jed E. Rose, Ph.D. |
|---|---|
| Organization | Rose Research Center |
| Phone | 9193282345 |
| jed.rose@roseresearchcenter.com |
- EVAR