Assisting Smokers to Switch to an e-Cigarette by Accelerating Learning of Adaptive Habits Using D-cycloserine

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the effects of a reward devaluation strategy, which has been researched in the past, combined/augmented with the medication d-cycloserine in assisting smokers to switch from combustible cigarette (CC) to Juul.

Official Title
-----------------
Assisting Smokers to Switch to an e-Cigarette by Accelerating Learning of Adaptive Habits Using D-cycloserine

Conditions
-----------------
Smoking Cessation, Harm Reduction

Intervention / Treatment
-----------------
* Drug: d-cycloserine
* Other: Juul e-cigarette


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Has signed the informed consent form (ICF) and is able to understand the information provided in the ICF. Is 22 to 65 years of age (inclusive) at screening. Smokes ≥ 10 commercially available CCs per day (no brand restrictions), for the last 12 months. Expired air CO reading of at least 10 ppm as assessed at the screening session. 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, ECG, concomitant medications and medical history). Patient Health Questionnaire (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 mm Hg, diastolic >95 mm Hg) 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 within 30 days of screening, or during the study. Taking antidepressants or psychoactive medications (e.g., antipsychotics, antidepressants, benzodiazepines, hypnotics). Use of any of these products in the past 30 days: Illegal drugs (or if the urine drug screen is positive for cocaine, tetrahydrocannabinol (THC), amphetamines, methamphetamines, or opiates); Experimental (investigational) drugs that are unknown to participant; Chronic opiate use; Medications to treat tuberculosis (e.g., isoniazid, ethionamide). 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 positive pregnancy test.

Ages Eligible for Study
-----------------
Minimum Age: 22 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DCS with Juul e-cigarette<br>d-cycloserine (DCS) 100 mg taken orally, once a day for six weeks. There will be a 50 mg dose taken the afternoon/evening prior to the first switch date (after enrollment) to ensure serum levels of the medication are available for the first switch to e-cigarette attempt. Participants will be instructed to use the Juul as often as they like during the 12 week period, and to switch completely to the Juul within 1 week. If, however, they do smoke any combustible cigarettes (CC), they will also be instructed to use the Juul immediately before each CC to relieve their craving as much as possible before smoking their usual brand. The Juul will also be the first product that they are instructed to use each morning. Smokers will be told to try to completely substitute Juul for CCs by the end of the first week of use. | Drug: d-cycloserine<br>* d-cycloserine (DCS) 100 mg taken orally, once a day for six weeks.<br>Other: Juul e-cigarette<br>* Juul use as often as the participant likes for 12 weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Smoking Abstinence based on Self-Report | 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. | During weeks 3-6 and 9-12 post-switching date. | 
| Smoking Abstinence based on Expired Air Carbon Monoxide (CO) | Complete switching from combustible cigarette use at each time point will be confirmed by an expired air CO reading of less than 5 ppm. | End of Week 6, End of Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in Cigarettes Per Day | Reduction in the number of reports cigarettes smoked per day over the previous seven days (at each time point) compared to baseline. | Week 6, Week 12, Six-Month Follow-Up | 
| Reduction in Expired Air Carbon Monoxide (CO) | Reduction in Expired Air Carbon Monoxide (CO) compared to baseline. | End of Week 6, End of Week 12 | 
| Change in rewarding effects for cigarettes and e-cigarettes at 6 weeks post switch | o assess subjective satisfaction and other perceived rewarding or aversive effects accompanying e-cigarette use and combustible cigarette use using the modified (e-Cigarette) Cigarette Evaluation Questionnaire. This questionnaire contains five subscale scores: smoking satisfaction (satisfying, tastes good, enjoy smoking), psychological rewards (calms down, more awake, less irritable, helps concentrate, reduces hunger), aversion (dizziness, nauseated), enjoyment of respiratory tract sensations (single-item assessment), craving reduction (single-item assessment). Participants will be asked to assess the 12 items of the questionnaire on a 7-point scale, ranging from 1-not at all to 7-extremely. | End of Week 6 |