Evaluating the Comparative Pharmacokinetics of Nicotine After Administration Via JUUL or Tobacco Cigarettes

• ClinicalTrials.gov Identifier: NCT04053868
• Recruitment Status: Recruiting
• First Posted: August 13, 2019
• Last Update Posted: May 4, 2022
• Sponsor: University of California, San Francisco
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): University of California, San Francisco

Study Description

Brief Summary:

This is an observational, crossover design that will examine the pharmacokinetics and pharmacodynamics of impact of smoking tobacco cigarettes or vaping the JUUL electronic cigarette.

Condition or disease	Intervention/treatment	Phase
Nicotine Administration & Dosage; E-cigarettes; Vaping; E-Liquid; Tobacco Smoking	Other: JUUL; Other: Tobacco	Not Applicable

Detailed Description:

The goal of this study is to better understand the pharmacokinetic and pharmacodynamics responses produced by the JUUL e-cigarette, compared to tobacco cigarettes, in e-cigarette and tobacco cigarette smokers.

Specific Aim #1- To categorize the nicotine pharmacokinetic (PK) profile (maximum plasma concentration; time to maximum plasma concentration and area under the concentration-time curve) and compare when using the JUUL e-cigarette vs. a tobacco cigarette in a standardized manner.

Specific Aim #2- To categorize the nicotine PK profile (maximum plasma concentration; time to maximum plasma concentration and area under the concentration-time curve(AUC)) and compare when using the JUUL e-cigarette vs a tobacco cigarette when using the product ad libitum.

Specific Aim #3- To evaluate various outcomes following JUUL e-cigarette or tobacco cigarette use, both with standardized and ad lib use including: heart rate, plasma catecholamines, pulmonary function testing.

Specific Aim #4- To evaluate and compare the effects on craving, reward and satisfaction when using the JUUL e-cigarette vs. tobacco cigarette.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Evaluating the Comparative Pharmacokinetics of Nicotine After Administration Via JUUL or Tobacco Cigarettes
• Actual Study Start Date: December 9, 2019
• Estimated Primary Completion Date: August 31, 2022
• Estimated Study Completion Date: August 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Electronic Cigarette; The participants will participate in a standardized vaping session using a JUUL E-cigarette device with a JUUL e-liquid pod.	Other: JUUL; Electronic Cigarette
Experimental: Tobacco Cigarette; The participants will participate in a standardized smoking session using commercial tobacco cigarettes.	Other: Tobacco; Tobacco Cigarette

Outcome Measures

Primary Outcome Measures :

1. Nicotine Exposure [ Time Frame: 6 Hours ]
   Plasma nicotine area under the concentrated time curve (AUC) (ng/ml*h)

Secondary Outcome Measures :

1. Cardiovascular Effects: Heart Rate [ Time Frame: Hospital Days 1-2 ]
   Participant heart rate will be measured in beats per minute throughout both inpatient stays on each arm.
2. Cardiovascular Effects: Systolic Blood Pressure [ Time Frame: Hospital Days 1-2 ]
   Participant systolic blood pressure will be taken during e-cigarette and/or tobacco cigarette use on each arm.
3. Cardiovascular Effects: Diastolic Blood Pressure [ Time Frame: Hospital Days 1-2 ]
   Participant diastolic blood pressure will be taken during e-cigarette and/or tobacco cigarette use on each arm.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Healthy on the basis of medical history and limited physical examination, as described below:
• - Heart rate < 105 beats per minute (bpm)
• - - Considered out of range if both machine and manual readings are above/below these thresholds.
• - Systolic Blood Pressure < 160 and > 90*
• - Diastolic Blood Pressure < 100 and > 50*
• Age: >= 21 & <=70 years old
• Body Mass Index (BMI) <= 38.0 (at PI's discretion for higher BMI if no other concurrent health issues)
• Willingness to avoid combusted marijuana up to 48 hours before each study visit
• Nicotine strength of e-liquid of usual e-cigarette > 0 mg/ml
• Group 1 Experienced E-cigarette users
• - Current use of tobacco cigarettes (<5 cigarettes per day)
• - Current e-cigarette use at least 15 days out of the past 30 days of a non-mod e-cigarette
• Group 2 Primary Tobacco cigarette users:
• - Currently smoking >= 5 cigarettes per day
• - Current e-cigarette use must be < 5 times per month
• Saliva cotinine >=50 ng/ml or urine cotinine and/or NicAlert=6
• Must have a smart phone, computer, or tablet and internet access (for remote procedures)

Exclusion Criteria:

• Medical
• - Heart disease
• - Seizures
• - Cancer
• - Thyroid disease (okay if controlled with medication)
• - Diabetes
• - Hepatitis B or C or Liver disease
• - Glaucoma
• - Kidney disease or urinary retention
• - History of stroke
• - An ulcer in the past year
• - Active use of an inhaler for Asthma or Chronic Obstructive Pulmonary Disease (COPD)
• Psychiatric conditions
• - Current or past schizophrenia, and/or current or past bipolar disorder
• - Major depression, current or within the past year
• - Major personality disorder
• - Participants with current or past minor or moderate depression and/or anxiety disorders will be reviewed by the principal investigator (PI) and/or medical monitor and considered for inclusion
• - History of psychiatric hospitalizations are not exclusionary, but study participation will be determined as per PI's or medical monitor's approval
• Drug/Alcohol Dependence
• - Alcohol or illicit drug dependence within the past 12 months with the exception of those who have recently completed an alcohol/drug treatment program
• - Positive toxicology test for illicit drugs at the screening visit (Tetrahydrocannabinol (THC) & prescribed medications okay)
• - Opioid replacement therapy (including methadone, buprenorphine, or other)
• Psychiatric medications
• - Current regular use of any psychiatric medications is exclusionary, with the exception of Selective Serotonin Reuptake Inhibitor (SSRI) and serotonin-norepinephrine reuptake Inhibitor (SNRI) and current evaluation by the PI and/or medical monitor that the participant is otherwise healthy, stable, and able to participate
• Medications
• - Use of sympatholytic medications for cardiovascular conditions including hypertension (Example: beta and alpha-blockers)
• - Use of medications that are inducers of nicotine metabolizing enzyme CYP2A6 (Example: rifampicin, carbamazepine, phenobarbital, and other anticonvulsant drugs)
• - Concurrent use of nicotine-containing medications
• - Any stimulant medications (example: Adderall) generally given for attention deficit hyperactivity disorder (ADHD) treatment
• Use of Other Tobacco Products (OTP)
• - Any of the following products in combination more than 15 times in the past month
• - - smokeless tobacco (snus, oral snuff, chewing tobacco)
• - - pipes
• - - cigars, cigarillos, little cigars
• - - blunts, spliffs
• - - hookah
• Other/Misc. Chronic Health Conditions
• Fainting (within the last 30 days)
• Other "life threatening illnesses" as per PI's or medical monitor's discretion
• Pregnancy
• - Pregnancy (self-reported and urine pregnancy test)
• - Breastfeeding (determined by self-report)
• Concurrent participation in another clinical trial (at PI's discretion)
• Inability to read and write in English
• Planning to quit smoking or vaping within the next 60 days
• Recent onset or change (worsening) in cough, fever and/or abdominal symptoms (vomiting or pain) in the past two weeks
• Diagnosis of pneumonia in the past 3 months
• Uncomfortable with blood draws
• Known allergy to propylene glycol or vegetable glycerin

Contacts and Locations

Contacts

Contact: Lisa Lawrence; 415-608-4864; Lisa.Lawrence@ucsf.edu

Contact: Jeremy P Giberson; 415-706-6023; jeremy.giberson@ucsf.edu

Locations

United States, California

Zuckerberg San Francisco General Hospital; Recruiting

San Francisco, California, United States, 94110

Contact: Jeremy P Giberson, BS 415-706-6023 jeremy.giberson@ucsf.edu

Contact: Sundos Yassin, BS (628) 206-8955 sundos.yassin@ucsf.edu

Principal Investigator: Neal L Benowitz, MD

Sub-Investigator: Gideon St. Helen, PhD

University of California, San Francisco; Recruiting

San Francisco, California, United States, 94143

Contact: Jeremy P Giberson, BS 415-706-6023 jeremy.giberson@ucsf.edu

Contact: Sundos Yassin (628) 206-8955 sundos.yassin@ucsf.edu

Principal Investigator: Neal L Benowitz, MD

Sub-Investigator: Gideon St. Helen, PhD

Sponsors and Collaborators

University of California, San Francisco

National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Neal L Benowitz, MD; University of California, San Francisco

More Information

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT04053868
• Other Study ID Numbers: 19-28309; 2R01DA039264-04A1 ( U.S. NIH Grant/Contract )
• First Posted: August 13, 2019
• Last Update Posted: May 4, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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