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Short-Term Cardiovascular Effects of E-Cigarettes: Influence of E-Liquid pH (TCORS-2)

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ClinicalTrials.gov Identifier: NCT04449510
Recruitment Status : Not yet recruiting
First Posted : June 26, 2020
Last Update Posted : July 16, 2020
Sponsor:
Collaborators:
National Institutes of Health (NIH)
Food and Drug Administration (FDA)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of California, San Francisco

Tracking Information
First Submitted Date  ICMJE June 24, 2020
First Posted Date  ICMJE June 26, 2020
Last Update Posted Date July 16, 2020
Estimated Study Start Date  ICMJE August 31, 2020
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 24, 2020)
  • Nicotine Exposure: Blood Nicotine [ Time Frame: Day 1 of each Arm ]
    Concentration of plasma nicotine (ng/ml) will be used to assess differences across the three e-liquid pH levels.
  • Nicotine Exposure: Saliva pH [ Time Frame: Day 1 of each Arm ]
    Participant saliva pH will be measured before and during outpatient stay.
  • Subjective Effects: Withdrawal [ Time Frame: Day 1 of each Arm ]
    We will compile a score for the subjective effect of withdrawal using the sum of points scored on the Minnesota Nicotine Withdrawal Scale (MNWS), where a higher score (score range from 0 points to 60 points) indicates a higher intensity of the indicated subjective effect.
  • Subjective Effects: Craving [ Time Frame: Day 1 of each Arm ]
    We will compile a score for the subjective effect of craving using the sum of points scored in the two subscales (intention and desire to engage in smoking behavior that is anticipated as pleasant, and anticipation of relief from negative affect through smoking) of the Questionnaire of Smoking Urges (QSU-Brief), where a higher score (score range from 10 points to 70 points) indicates a higher intensity of the indicated subjective effect.
  • Subjective Effects: Reward [ Time Frame: Day 1 of each Arm ]
    We will compile a score for the subjective effect of reward using the sum of points scored in the five subscales (Smoking Satisfaction - score range from 1 point to 7 points; Psychological Reward - score range from 5 points to 35 points; Aversion - score range from 2 points to 14 points; Enjoyment of Respiratory Tract Sensations - score range from 2 points to 14 points; and Craving Reduction - score range from 1 point to 7 points) of the modified Cigarette Evaluation Scale (mCES), where a higher score indicates a higher intensity of the indicated subjective effect.
  • Cardiovascular Effects: Heart Rate [ Time Frame: Day 1 of each Arm ]
    Participant heart rate will be measured in beats per minute throughout the outpatient stay.
  • Cardiovascular Effects: Skin Blood Flow [ Time Frame: Day 1 of each Arm ]
    Participant skin blood flow will be measured by product of average blood cell velocity and concentration in mL/min during outpatient stay.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 24, 2020)
  • Vaping Topography: Puff Number [ Time Frame: Day 1 of each Arm ]
    Vaping topography measures will be obtained from frame by frame analysis of high definition videos during the ad libitum sessions and measured as puffs per minute.
  • Vaping Topography: Puff Duration [ Time Frame: Day 1 of each Arm ]
    Vaping topography measures will be obtained from frame by frame analysis of high definition videos during the ad libitum sessions and measured as seconds per puff.
  • Vaping Topography: Inter-Puff Interval [ Time Frame: Day 1 of each Arm ]
    Vaping topography measures will be obtained from frame by frame analysis of high definition videos during the ad libitum sessions and measured as seconds/minutes between puffs.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Short-Term Cardiovascular Effects of E-Cigarettes: Influence of E-Liquid pH
Official Title  ICMJE Short-Term Cardiovascular Effects of E-Cigarettes: Influence of E-Liquid pH
Brief Summary This study will examine the short-term cardiovascular (CV) effects of e-liquid pH in a randomized, crossover clinical and behavioral pharmacology study of experienced adult e-cigarette users (N=21). The specific aim of the study is to assess the impact of changes in e-liquid pH on nicotine pharmacokinetics, cardiovascular, and subjective effects of e-cigarettes.
Detailed Description

This is a single-site, randomized, crossover study of experienced adult e-cigarette users to assess nicotine exposure, toxicant exposure, and the short-term CV effects of e-liquid pH. Three e-liquid pH conditions will be assessed on all participants: 5, 7, and 9.

Hypothesis 2a: The rate of systemic nicotine absorption is inversely related to e-liquid pH and results in lower peak blood nicotine levels at higher pH.

Hypothesis 2b: Heart rate acceleration will decrease and subjective measures of sensation in the throat, reward, and satisfaction will increase with increasing e-liquid pH.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Cardiovascular Risk Factor
  • Nicotine Dependence
Intervention  ICMJE Other: Electronic Cigarette
E-cigarette Device: The delivery device will be a variable wattage all-in-one device with operating wattage of 7.0 - 75.0 W. The device will be set at 10 watts for the study visits.
Study Arms  ICMJE
  • E-liquid pH 5, 7, or 9
    Using an electronic cigarette, the patient will participate in a standardized vaping session using 1 of 3 assigned e-liquid pH.
    Intervention: Other: Electronic Cigarette
  • 1 of the other 2 remaining e-liquid pH
    Using an electronic cigarette, the patient will participate in a standardized vaping session using 1 of the other 2 assigned e-liquid pH.
    Intervention: Other: Electronic Cigarette
  • Remaining e-liquid pH
    Using an electronic cigarette, the patient will participate in a standardized vaping session using the remaining assigned e-liquid pH.
    Intervention: Other: Electronic Cigarette
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: June 24, 2020)
21
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2021
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Heart rate < 105 beats per minute (BPM)*
  • Systolic Blood pressure <160 and > 90*
  • Diastolic Blood Pressure <100 and > 50*
  • Body Mass Index (BMI) < 38.0 (at investigator's discretion for higher BMI if no other concurrent health issues)

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

  • Use e-cigarettes on at least 15 days in the past 30 for at least 3 months
  • Smoke 10 or fewer cigarettes/tobacco products per day in the last 30 days
  • Willing to use mod e-cigarette
  • Willing to abstain from tobacco product use for night before study
  • Age: > 21 years old and < 70 years old
  • Using e-liquid > 0mg/ml nicotine
  • Saliva cotinine of ≥ 30 ng/ml or NicAlert=6 (in cases where lab turn around time will delay study procedure)

Exclusion Criteria:

  • Seizures
  • Cancer
  • Hepatitis B or C or Liver Disease
  • Oral Thrush
  • Heart disease
  • Glaucoma
  • Kidney disease or urinary retention
  • Diabetes
  • High Blood Pressure (taking sympatholytic medications such as alpha and beta blockers)
  • History of stroke
  • An ulcer in the past year
  • Thyroid disease (okay if controlled with medication)
  • 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 study physician and considered for inclusion.
  • History of psychiatric hospitalizations are not exclusionary, but study participation will be determined as per study physician's approval
  • Recent onset or change in cough, fever and/or abdominal symptoms (vomiting or pain) in the past two weeks. (If yes, participant can re-screen when symptoms resolve).
  • 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 at the screening visit (THC & prescribed medications okay)
  • Opioid replacement therapy (including methadone, buprenorphine, or other)
  • Positive urine cannabis is not exclusionary but participant must report use of cannabis and agree to abstain from cannabis use for the duration of the study
  • Psychiatric medications
  • Current regular use of any psychiatric medications with the exception of Selective Serotonin Reuptake Inhibitor (SSRI) and serotonin-norepinephrine reuptake Inhibitor (SNRIs) and current evaluation by the study physician that the participant is otherwise healthy, stable, and able to participate.
  • Medications
  • Use of medications that are inducers of nicotine metabolizing enzyme CYP2A4 (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 sympatholytic medications that affect cardiovascular conditions including hypertension, (Example: beta and alpha-blockers)
  • Other/Misc. Chronic Health Conditions
  • Fainting (within the last 30 days)
  • Other "life threatening illnesses" as per study physician's discretion
  • Pregnancy
  • Pregnancy (self-reported and urine pregnancy test)
  • Breastfeeding (determined by self-report)
  • Concurrent participation in another clinical trial
  • Inability to communicate in English
  • Planning to quit vaping within the next 60 days
  • Uncomfortable with getting blood drawn
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Aileen Macaraeg, BS 415-608-3419 aileen.macaraeg@ucsf.edu
Contact: Jennifer Ko, BS 628-206-4244 jennifer.ko@ucsf.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04449510
Other Study ID Numbers  ICMJE 20-30597
2U54CA180890-06 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of California, San Francisco
Study Sponsor  ICMJE University of California, San Francisco
Collaborators  ICMJE
  • National Institutes of Health (NIH)
  • Food and Drug Administration (FDA)
  • National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Gideon St. Helen, PhD University of California, San Francisco
PRS Account University of California, San Francisco
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP