Clinical trial NCT04053868: Evaluating the Comparative Pharmacokinetics of Nicotine After Administration Via JUUL or Tobacco Cigarettes
Official title: Evaluating the Comparative Pharmacokinetics of Nicotine After Administration Via JUUL or Tobacco Cigarettes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Nicotine Administration & Dosage
E-cigarettes
Vaping
E-Liquid
Tobacco Smoking
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2019-08-13
Enrollment: 17
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility 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

Primary outcomes:
measure: Mean Nicotine Exposure
timeFrame: Plasma collected at baseline (prior to any product use) and at 2, 5, 7, 10, 15, 30, 60, 90, and 118 minutes after end of standardized session.
Secondary outcomes:
measure: Overall Mean Heart Rate Over Time
timeFrame: Up to 118 minutes after end of standardized session.
measure: Mean Systolic Blood Pressure Over Time
timeFrame: Up to 118 minutes after end of standardized session.
measure: Mean Diastolic Blood Pressure Over Time
timeFrame: Up to 118 minutes after end of standardized session.
measure: Mean Questionnaire of Smoking Urges (QSU) and Modified for E-cigarettes (mQSU) Score Over Time
timeFrame: Up to 118 minutes after end of standardized session
measure: Mean Minnesota Nicotine Withdrawal Scale (MNWS) Score Over Time
timeFrame: Up to 118 minutes after end of standardized session.
measure: Mean Cigarette Evaluation Scale (CES) and Modified for E-cigarettes (mCES) Score Over Time
timeFrame: Up to 240 minutes after end of standardized session
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General Hospital
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Neal L Benowitz, MD
role: PRINCIPAL_INVESTIGATOR
References: