Combination of E-cigarettes and Varenicline for Tobacco Harm Reduction (EVAR)

• ClinicalTrials.gov Identifier: NCT04210180
• Recruitment Status: Completed
• First Posted: December 24, 2019
• Results First Posted: February 8, 2022
• Last Update Posted: February 24, 2022
• Sponsor: Rose Research Center, LLC
• Collaborator: Foundation for a Smoke Free World INC
• Information provided by (Responsible Party): Jed Rose, Rose Research Center, LLC

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
Smoking Cessation; Harm Reduction	Drug: Varenicline; Other: e-cigarette	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Combination of E-cigarettes and Varenicline for Tobacco Harm Reduction
• Actual Study Start Date: November 19, 2019
• Actual Primary Completion Date: October 14, 2020
• Actual Study Completion Date: March 22, 2021

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 Name: Chantix; Other: e-cigarette; Each G6 prefilled cartomizer contains a 50/50 blend nicotine salt with 35mg nicotine strength.; Other Name: Halo G6

Outcome Measures

Primary Outcome Measures :

1. Number of Participant Reporting Continuous Complete Switching From Cigarettes to Halo G6 [ Time Frame: 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.
2. Number of Participants Confirmed (by Expired Air CO) to Have Switched From Cigarettes to Halo G6 [ Time Frame: 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 :

1. Number of Participants Reporting Point Abstinence From Smoking Cigarettes at 6 Months Post-Switch [ Time Frame: 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:

1. Mean Changes in Arterial Flow When Smokers Switch From Cigarettes to E-cigarettes [ Time Frame: 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

• Ages Eligible for Study: 21 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Has signed the ICF and is able to read and understand the information provided in the consent form.
2. Is 21 to 65 years of age (inclusive) at screening.
3. Smokes at least 10 commercially available cigarettes per day (no brand restrictions), for the last 12 months.
4. Has an expired air carbon monoxide reading of at least 10 ppm at screening.
5. Interested in switching to an electronic cigarette.
6. Willing and able to comply with the requirements of the study.
7. Owns a smart phone with text message and data capabilities compatible with necessary surveys.

Exclusion Criteria:

1. 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).
2. 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.
3. Planned use of an FDA-approved smoking cessation product during the study.
4. High blood pressure (systolic > 150 mmHg or diastolic >95 mmHg) at screening.
5. Body mass index (BMI) less than 15.0 kg/m2 or greater than 40.0 kg/m2.
6. 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.
7. Has received psychotherapy or behavioral treatments potentially impacting symptoms of depression, anxiety, or nicotine withdrawal within 30 days of screening, or during the study.
8. Taking antidepressants, psychoactive medications (e.g. antipsychotics, benzodiazepines, hypnotics) or medications that prolong QTc.
9. 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); b. Experimental (investigational) drugs that are unknown to subject; c. Chronic opiate use.
10. 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.
11. Pregnant or nursing (by self-report) or has a positive pregnancy test.
12. Enrollment requirements met.

Contacts and Locations

Locations

United States, North Carolina

Rose Research Center

Charlotte, North Carolina, United States, 28262

Rose Research Center

Raleigh, North Carolina, United States, 27617

Sponsors and Collaborators

Rose Research Center, LLC

Foundation for a Smoke Free World INC

  Study Documents (Full-Text)

Documents provided by Jed Rose, Rose Research Center, LLC:

Study Protocol and Statistical Analysis Plan  [PDF] March 23, 2020

More Information

• Responsible Party: Jed Rose, President and CEO, Rose Research Center, LLC
• ClinicalTrials.gov Identifier: NCT04210180
• Other Study ID Numbers: EVAR
• First Posted: December 24, 2019
• Results First Posted: February 8, 2022
• Last Update Posted: February 24, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Varenicline; Nicotinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs