Vaping High vs. Low Nicotine E-Liquid

This study will examine the effects of electronic cigarette e-liquid nicotine content in a randomized, crossover clinical and behavioral pharmacology study of experienced adult e-cigarette users (N=36). The specific aim is to determine the impact of nicotine content of e-liquid on nicotine pharmacology, systemic exposure to toxic volatile organic compounds, and short-term cardiovascular effects.

Study Overview

• Status: Withdrawn
• Conditions: Cardiovascular Risk Factor; Nicotine Dependence
• Intervention / Treatment: Other: Low Nicotine E-Liquid; Other: Medium or High Nicotine E-Liquid

Detailed Description

This is a within-subjects, crossover design of advanced electronic cigarette users in which we will examine nicotine pharmacokinetics, subjective effects, daily nicotine intake and nicotine titration, short-term cardiovascular effects, and toxicant exposure when participants are using low vs. high nicotine e-liquids.

Hypothesis 1: E-cigarette users will titrate their intake of nicotine such that they will inhale fewer aerosol toxicants and suffer less harm to health when using higher vs. lower nicotine content e-liquids.

Hypothesis 2: Compared to low nicotine, high nicotine e-liquid use will have similar cardiovascular effects throughout the day (due to compensatory behavioral changes), with similar effects on heart rate, blood pressure, and catecholamine release.

Hypothesis 3: Exposure to volatile organic compounds (VOCs) will be lower when vaping high nicotine e-liquids compared to low nicotine e-liquids.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94110
      • University of California, San Francisco
    • San Francisco, California, United States, 94110
      • Zuckerberg San Francisco General Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Healthy on the basis of medical history and limited physical examination, as described below:
• Heart rate < 105 beats per minute (BPM)*
• Systolic Blood Pressure < 160 and > 90*

• Diastolic Blood Pressure < 100 and > 50*

  *Considered out of range if both machine and manual readings are above/below these thresholds.

• Age: >= 21 years
• Age: <= 70 years
• Current regular user of open tank electronic cigarette (EC) (at least 20 times in the past 30 days) with e-liquid nicotine of 3-6 mg/mL.
• Non-smoker or non-daily cigarette smokers agreeing to abstain from cigarettes for the duration of the study.
• Saliva cotinine >50 ng/mL and/or NicAlert=6
• Carbon monoxide >= 5 ppm or per discretion of Principal Investigator

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 PI and considered for inclusion
• History of psychiatric hospitalizations is not exclusionary, but study participation will be determined as per PI'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 (THC & prescribed medications okay)
• Opioid replacement therapy (including methadone, buprenorphine, or other)
• Psychiatric medications
• Current regular use of any psychiatric medications with the exception of Selective Serotonin Reuptake Inhibitors (SSRIs) and serotonin-norepinephrine reuptake Inhibitors (SNRIs) and current evaluation by the PI that the participant is otherwise healthy, stable, and able to participate.
• Medications
• Use of medications that are inducers of nicotine metabolizing enzyme CYP2A6 (Example: rifampicin, carbamazepine, phenobarbital, and other anticonvulsant drugs).
• Use of sympatholytic medications for cardiovascular conditions including hypertension (Example: beta and alpha-blockers)
• Concurrent use of nicotine-containing medications
• Any stimulant medications (example: Adderall) generally given for attention deficit hyperactivity disorder (ADHD) treatment
• Other/Misc. Chronic Health Conditions
• Oral thrush
• Fainting (within the last 30 days)
• Other "life threatening illnesses" as per PI's discretion
• Pregnancy
• Pregnancy (self-reported and urine pregnancy test)
• Breastfeeding (determined by self-report)
• Concurrent participation in another clinical trial
• Inability to read and write in English
• Planning to quit vaping within the next 60 days
• Concurrent regular use of marijuana (occasional users of these products may be enrolled if they agree to abstain from their use during the period of the study)
• Use of other tobacco products, smokeless tobacco, pipes, cigars/cigarillos, blunts/spliffs (no more than 10 times in the past month and must agree to abstain from their use during the period of the study)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Low Nicotine; Using an electronic cigarette, the patient will participate in a standardized vaping session using 3 mg/ml nicotine e-liquid.	Other: Low Nicotine E-Liquid; Participants will vape e-liquid with nicotine concentration of 3 mg/ml.
Other: Medium or High Nicotine; The patient will participate in a standardized vaping session using either an electronic cigarette with 18 mg/ml nicotine e-liquid or a JUUL device with a JUUL e-liquid pod.	Other: Medium or High Nicotine E-Liquid; Participants will vape either e-liquid with nicotine concentration of 18 mg/ml or a JUUL device with JUUL pod of 59 mg/ml nicotine e-liquid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular Effects: Heart Rate	Participant heart rate will be measured in beats per minute throughout the inpatient stay.	Days 1-3 of each Arm
Nicotine Exposure	Plasma nicotine area under curve (AUC) (ng/ml*h)	Day 1 of each Arm
Cardiovascular Effects: Systolic Blood Pressure	Participant systolic blood pressure will be taken for 24 hours during ad-lib e-cigarette use.	Day 2 of each Arm
Cardiovascular Effects: Diastolic Blood Pressure	Participant diastolic blood pressure will be taken for 24 hours during ad-lib e-cigarette use.	Day 2 of each Arm

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vaping Topography: Puff Number	Vaping topography measures will be obtained from self-reported participant vaping log during the ad libitum sessions and measured as puffs per minute.	Days 1-3 of each Arm
Vaping Topography: Puff Duration	Vaping topography measures will be obtained from self-reported participant vaping log during the ad libitum sessions and measured as seconds per puff.	Days 1-3 of each Arm
Vaping Topography: Inter-Puff Interval	Vaping topography measures will be obtained from self-reported participant vaping log during the ad libitum sessions and measured as seconds/minutes between puffs.	Days 1-3 of each Arm

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Neal Benowitz, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2023
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: August 5, 2019
• First Submitted That Met QC Criteria: August 5, 2019
• First Posted (Actual): August 7, 2019

Study Record Updates

• Last Update Posted (Actual): August 22, 2023
• Last Update Submitted That Met QC Criteria: August 17, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Vaping; E-Cigarettes; E-Cig Mods; E-Liquid
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: 19-27571; 5R01DA031193 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No