Evaluation of the Electronic Cigarette Withdrawal Syndrome

• ClinicalTrials.gov Identifier: NCT06066996
• Recruitment Status: Recruiting
• First Posted: October 4, 2023
• Last Update Posted: December 6, 2023
• Sponsor: Johns Hopkins University
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
E-cigarette Use; Withdrawal	Drug: Transdermal Nicotine Patch; Drug: Placebo Nicotine Patch	Early Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Evaluation of the Electronic Cigarette Withdrawal Syndrome: Mechanistic Targets for Intervention
• Actual Study Start Date: November 28, 2023
• Estimated Primary Completion Date: August 31, 2028
• Estimated Study Completion Date: August 31, 2028

Arms and Interventions

Arm	Intervention/treatment
Experimental: Transdermal Nicotine Patch; 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; Blinded Nicotine Patch
Placebo Comparator: Transdermal Placebo Patch; 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; Blinded Patch with No Nicotine
No Intervention: No Patch; Participants assigned to this condition will not receive a patch.

Outcome Measures

Primary Outcome Measures :

1. Change in Hughes-Hatsukami Withdrawal Scale [ Time Frame: Baseline, every 4 hours up to 16 hours ]
   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.
2. Change in Smoking urges as assessed by the Tiffany-Drobes Questionnaire of Smoking Urges (QSU) Brief [ Time Frame: Baseline, every 4 hours up to 16 hours ]
   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.
3. Change in Positive and Negative Affect Schedule (PANAS) [ Time Frame: Baseline, every 4 hours up to 16 hours ]
   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.
4. Change in Conners' Continuous Performance Task (CPT) [ Time Frame: Baseline, every 4 hours up to 16 hours ]
   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.
5. Change in Memory as assessed by the N-Back [ Time Frame: Baseline, every 4 hours up to 16 hours ]
   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.
6. Total sleep time [ Time Frame: Nightly up to seven days ]
   Total time sleeping in minutes measured using actigraphy and unobtrusive EEG.
7. Total time spent in Rapid eye movement (REM) sleep [ Time Frame: Nightly up to seven days ]
   Total time sleeping in minutes in REM stage measured using actigraphy and unobtrusive EEG.
8. Wake after sleep onset (WASO) [ Time Frame: Nightly up to seven days ]
   Total number of minutes that a person is awake after having initially fallen asleep measured using actigraphy and unobtrusive EEG.

Secondary Outcome Measures :

1. Change in E-Cigarette Demand Intensity [ Time Frame: Baseline, every 4 hours up to 16 hours ]
   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.
2. Change in E-Cigarette Demand Elasticity [ Time Frame: Baseline, every 4 hours up to 16 hours ]
   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.
3. Return to Use [ Time Frame: Day 14 ]
   Return to e-cigarette use at the one week follow-up.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion criteria:

1. 21-55 years old
2. good general health as reviewed by study medical team
3. vital signs in normal range as reviewed by study medical team
4. negative urine test for illicit drug use (excluding THC) and negative breath alcohol test
5. daily use of a nicotine-containing e-cigarette for at least 6 months
6. no regular use of other tobacco products (e.g., smokeless products) for at least 6 months
7. urine cotinine >100ng/mL (i.e., recommended cutoff for confirming current nicotine use)
8. exhaled breath carbon monoxide (CO) <6ppm
9. Penn State E-cigarette Dependence (PSED) score >=4, indicating mild dependence or greater
10. have an interest in reducing e-cigarette use

Exclusion criteria:

1. psychoactive drug use (aside from cannabis, nicotine, alcohol, caffeine) in past month
2. current use of over-the-counter (OTC) or prescription medications that may impact safety
3. use cannabis >2 times per week
4. history of or current significant medical condition that would impact participation or safety according to the study investigators and medical staff
5. 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
6. enrollment in another trial
7. positive pregnancy test
8. currently using a nicotine/tobacco cessation product
9. seizure disorder or traumatic brain injury (TBI)

Contacts and Locations

Contacts

Contact: Justin Strickland, Ph.D.; 4105501975; jstric14@jhmi.edu

Locations

United States, Maryland

Behavioral Pharmacology Research Unit; Recruiting

Baltimore, Maryland, United States, 21224

Contact: Justin Strickland, Ph.D. 410-550-1975 jstric14@jhmi.edu

Sponsors and Collaborators

Johns Hopkins University

National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Justin Strickland, Ph.D.; Johns Hopkins University

More Information

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT06066996
• Other Study ID Numbers: IRB00407275; R01DA057925 ( U.S. NIH Grant/Contract )
• First Posted: October 4, 2023
• Last Update Posted: December 6, 2023
• Last Verified: November 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Substance Withdrawal Syndrome; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Nicotine; Ganglionic Stimulants; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Nicotinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action