Evaluation of the Electronic Cigarette Withdrawal Syndrome

Study Overview
=================
Brief Summary
-----------------
The goal of this project is to rigorously evaluate the nature of e-cigarette withdrawal in exclusive e-cigarette users during a monitored abstinence period and the role of nicotine in the expression of this withdrawal syndrome.

Detailed Description
-----------------
This project will use a rigorous residential laboratory design to evaluate e-cigarette withdrawal expression and experimentally determine the role of nicotine in this syndrome. Healthy adults who exclusively use e-cigarettes will undergo monitored e-cigarette abstinence over seven days (1 week) in a residential unit. The investigators will evaluate the contribution of nicotine to withdrawal expression by assigning participants to one of three conditions: active nicotine patch, placebo patch control, or no patch to control for expectancies. Standardized behavioral and biological measures associated with withdrawal including patient report, cognitive task performance, and biometrics will be collected throughout to establish a rigorous timecourse of withdrawal and evaluate the contribution of nicotine to these symptoms.

Official Title
-----------------
Evaluation of the Electronic Cigarette Withdrawal Syndrome: Mechanistic Targets for Intervention

Conditions
-----------------
E-cigarette Use, Withdrawal

Intervention / Treatment
-----------------
* Drug: Transdermal Nicotine Patch
* Drug: Placebo Nicotine Patch


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: 21-55 years old good general health as reviewed by study medical team vital signs in normal range as reviewed by study medical team negative urine test for illicit drug use (excluding THC) and negative breath alcohol test daily use of a nicotine-containing e-cigarette for at least 6 months no regular use of other tobacco products (e.g., smokeless products) for at least 6 months urine cotinine >100ng/mL (i.e., recommended cutoff for confirming current nicotine use) exhaled breath carbon monoxide (CO) <6ppm Penn State E-cigarette Dependence (PSED) score >=4, indicating mild dependence or greater have an interest in reducing e-cigarette use Exclusion criteria: psychoactive drug use (aside from cannabis, nicotine, alcohol, caffeine) in past month current use of over-the-counter (OTC) or prescription medications that may impact safety use cannabis >2 times per week history of or current significant medical condition that would impact participation or safety according to the study investigators and medical staff current psychiatric condition or substance use disorder (aside from tobacco use disorder) that would impact participation or safety according to the study investigators and medical staff enrollment in another trial positive pregnancy test currently using a nicotine/tobacco cessation product seizure disorder or traumatic brain injury (TBI)

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 55 Years

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

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

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

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transdermal Nicotine Patch<br>Participants assigned to this condition will receive a blinded nicotine patch and will wear the patch on their upper arm, per the manufacturer's instructions. | Drug: Transdermal Nicotine Patch<br>* Blinded Nicotine Patch<br>|
| Placebo Comparator: Transdermal Placebo Patch<br>Participants assigned to this placebo nicotine patch condition will receive a blinded patch containing 0mg of nicotine, and will wear the patch on their upper arm, per the manufacturer's instructions. | Drug: Placebo Nicotine Patch<br>* Blinded Patch with No Nicotine<br>|
| No Intervention: No Patch<br>Participants assigned to this condition will not receive a patch. | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hughes-Hatsukami Withdrawal Scale | The Hughes-Hatsukami Withdrawal Scale consists of 13 items presented individually on a 100mm visual analog scale. Higher scores reflect higher withdrawal (worse outcome) [range 0-32]. Measures are taken at baseline, 8am, 12pm, 4pm, and 8pm every day during the seven day residential stay. | Baseline, every 4 hours up to 16 hours | 
| Change in Smoking urges as assessed by the Tiffany-Drobes Questionnaire of Smoking Urges (QSU) Brief | The Tiffany-Drobes QSU Brief consists of ten items, each presented on the screen as a phrase centered above seven boxes ranging from (strongly disagree) to (strongly agree). Higher scores reflect higher withdrawal (worse outcome) [range 0-70]. Measures are taken at baseline, 8am, 12pm, 4pm, and 8pm every day during the seven day residential stay. | Baseline, every 4 hours up to 16 hours | 
| Change in Positive and Negative Affect Schedule (PANAS) | The PANAS consists of 20 items presented individually on a five-point Likert scale. Higher scores reflect more positive affect and negative affect [range 0-50]. Measures are taken at baseline, 8am, 12pm, 4pm, and 8pm every day during the seven day residential stay. | Baseline, every 4 hours up to 16 hours | 
| Change in Conners' Continuous Performance Task (CPT) | On the CPT, participants respond to single letters appearing on their computer screen but are asked to refrain from responding to a specified letter(i.e., the letter X). Higher scores reflect more inattention. Measures are taken at baseline, 8am, 12pm, 4pm, and 8pm every day during the seven day residential stay. | Baseline, every 4 hours up to 16 hours | 
| Change in Memory as assessed by the N-Back | On the n-back, participants decide whether each stimulus in a sequence matches the one that appeared n items ago. Higher scores reflect more accuracy. Measures are taken at baseline, 8am, 12pm, 4pm, and 8pm every day during the seven day residential stay. | Baseline, every 4 hours up to 16 hours | 
| Total sleep time | Total time sleeping in minutes measured using actigraphy and unobtrusive EEG. | Nightly up to seven days | 
| Total time spent in Rapid eye movement (REM) sleep | Total time sleeping in minutes in REM stage measured using actigraphy and unobtrusive EEG. | Nightly up to seven days | 
| Wake after sleep onset (WASO) | Total number of minutes that a person is awake after having initially fallen asleep measured using actigraphy and unobtrusive EEG. | Nightly up to seven days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in E-Cigarette Demand Intensity | E-cigarette use at unconstrained price measured using a commodity purchase task. Higher scores reflect more demand (worse outcome). Measures are taken at baseline, 8am, 12pm, 4pm, and 8pm every day during the seven day residential stay. | Baseline, every 4 hours up to 16 hours | 
| Change in E-Cigarette Demand Elasticity | Sensitivity of e-cigarette use to price measured using a commodity purchase task. Higher scores reflect more price sensitivity (better outcome). Measures are taken at baseline, 8am, 12pm, 4pm, and 8pm every day during the seven day residential stay. | Baseline, every 4 hours up to 16 hours | 
| Return to Use | Return to e-cigarette use at the one week follow-up. | Day 14 |