Cigarette Harm Reduction With Electronic Cigarette Use

NCT03473483 | Withdrawn DMC

• 2 other identifiers: 17-23142U01DA045519
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is an observational, crossover study that will be examine use behaviors, chemical exposures, and biological effects of SREC compared to TC use in subjects confined to a research ward setting.

Conditions

Nicotine Dependence; Tobacco Toxicity; Nicotine Dependence, Cigarettes; Cardiovascular Risk Factor; Nicotine Withdrawal

Keywords

nicotine; tobacco; research electronic cigarette; e-cigarette; SREC

Outcome Measures

Primary Outcomes (8)

• Peak Nicotine Concentration

  Compare peak nicotine concentration between SREC vs. Tobacco Cigarette (TC) use

  Up to 2 years

• Time of Peak Nicotine Concentration

  Compare time of peak nicotine concentration between SREC vs. Tobacco Cigarette (TC) use

  Up to 2 years

• Mean overall systemic nicotine exposure

  Descriptive statistics will be used to examine systemic nicotine exposure from daily use of SREC and compare daily nicotine intake to TC use

  Baseline through study completion, approximately 2 years

• Change in Mean score on the Modified Cigarette Evaluation Questionnaire (mCEQ)

  The mCEQ use three multi-item domains (subscales) and two single items: "Smoking Satisfaction", "Psychological Reward", "Aversion", "Enjoyment of Respiratory Tract Sensations" and "Craving Reduction". Scores for each subscale are calculated as the average of its individual item responses of The items are rated on a seven-point scale ranging from 1 (not at all) to 7 (extremely). Higher scores indicate greater intensity of each smoking effect with, for example, greater satisfaction or psychological reward after smoking. Scores will be compared between SREC, TC, and dual use

  Baseline through study completion, approximately 2 years

• Patterns of puffing

  Compare the pattern of puffing between SREC and TC use by coding the recorded ad libitum use of SREC vs TC.

  Baseline through study completion, approximately 2 years

• Change in Mean score on the Minnesota Tobacco Withdrawal Scale-Revised (MTWS-R)

  The MTWS-R features two separate measures for examining the severity of nicotine withdrawal symptoms in a participant: a self-report scale and an observer scale. The observer scale asks the scale-taker to rate the severity of four symptoms in someone the they know who is experiencing nicotine withdrawal: "angry/irritable/frustrated," "anxious/tense," "depressed," and "restless/impatient." The self-report version asks for rankings of the severity of those same four symptoms, plus eleven others that cannot be observed by outsiders (including such things as "desire or craving to smoke," "insomnia, sleep problems, awakening at night," or "dizziness). Both scales use a Likert-type scale for the severity ratings, ranging from 0 ("not at all") to 4 ("severe"). These scores are tallied to calculate an a total withdrawal discomfort score and will be compared between SREC, TC, and dual use.

  Baseline through study completion, approximately 2 years

• Change in Mean score on the Questionnaire on Smoking Urges (QSU-Brief)

  The QSU-Brief consists of 10 statements about the respondent's feelings and thoughts about his or her desire to smoke cigarettes as he or she is completing the questionnaire (i.e., right now). Each response is scored a number ranging from 1 (strongly disagree) to 7 (strongly agree) and total scores are calculated by summing the item scores to compare craving between SREC, TC, and dual use.

  Baseline through study completion, approximately 2 years

• Change in Mean score on the Positive and Negative Affect Scale (PANAS)

  The Positive and Negative Affect Schedule (PANAS) is a brief scale is comprised of 20 items, with 10 items measuring positive affect (e.g., excited, inspired) and 10 items measuring negative affect (e.g., upset, afraid). Each item is rated on a five-point Likert Scale, ranging from 1 = Very Slightly or Not at all to 5 = Extremely, to measure the extent to which the affect has been experienced in a specified time frame and the final score is derived out of the sum of the ten items on both the positive and negative side. Scores can range from 10-50 for both the Positive and Negative Affect with the lower scores representing lower levels of Positive/Negative Affect and higher scores representing higher levels of Positive/Negative Affect. The scores will be comparted between SREC, TC, and dual use.

  Baseline through study completion, approximately 2 years

Secondary Outcomes (6)

• Changes in mean circadian heart rate

  Baseline through study completion, approximately 2 years

• Changes in mean blood pressure

  Baseline through study completion, approximately 2 years

• Changes in mean urinary catecholamine

  Baseline through study completion, approximately 2 years

• Mean Level of exposure to Tobacco smoke toxicant

  Baseline through study completion, approximately 2 years

• Sensitivity of anabasine or nicotelline to nicotine metabolites

  Baseline through study completion, approximately 2 years

Study Arms (3)

SREC only or cigarette only use

EXPERIMENTAL

Four days of SREC/Usual cigarette/product use as regular with daily diary. Admitted to hospital research ward on Day 5 and 6 for 2 hospital day visits that includes a standardized session of product use; 4-hr abstinence; pharmacokinetic (PK) blood draws; ad libitum use of product; cardiovascular (CV) monitoring, 12-hr urine collections, and 12-hr circadian blood draws.

Other: SREC

Alternate product from Arm 1

EXPERIMENTAL

Four days of SREC/Usual cigarette/product use as regular with daily diary. Admitted to hospital research ward on Day 5 and 6 for 2 hospital day visits that includes a standardized session of product use; 4-hr abstinence; PK blood draws; ad libitum use of product; CV monitoring, 12-hr urine collections, and 12-hr circadian blood draws.

Other: SREC

Standardized Dual Use

EXPERIMENTAL

Four days of SREC and/or usual product use as regular with daily diary. Admitted to hospital research ward on Day 5 and 6 for 2 hospital day visits that includes ad libitum SREC use and less than usual amount of cigarette use; CV monitoring, 12-hr urine collections, and 12-hr circadian blood draws.

Other: SREC

Interventions

SREC OTHER

The Standardized Research E-Cigarette (SREC) was developed by NIDA to help researchers assess uncertainties in electronic nicotine delivery devices. Tank: * Sealed and disposable * Minimum 350 puffs per tank * Volume of e-liquid per tank \~ 3ml E-Liquid Characteristics: * Tobacco flavored * Nicotine concentration: 15 mg/ml * Propylene Glycol:\~ 50% (wt / wt) * Glycerin: \~ 50% (wt / wt) * Cotinine: \<1 μg/g * Nornicotine: 5 μg/g * Myosmine : 3 μg/g * Anabasine: \<1 μg/g * Anatabine: \<1 μg/g * Beta:nicotyrine: \<1 μg/g * Diacetyl: \<2 μg/g * 2,3:Pentanedione: \<1 μg/g * Arsenic: \<0.1 μg/g * Cadmium: \<0.1 μg/g * Chromium: \<0.1 μg/g * Lead: \<0.1 μg/g * Nickel: \<0.1 μg/g * Mercury: \<0.05 μg/g

Also known as: Standardized Research E-Cigarette

Alternate product from Arm 1; SREC only or cigarette only use; Standardized Dual Use

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• \- Body Mass Index ≤ 38.0
• \- Expired Carbon Dioxide (CO) \>=5ppm
• Current regular "dual" user of both electronic cigarette (EC) and tobacco cigarette (TC)
• EC device use at least 10 or more days in the past 30 days
• Daily use of conventional TC (at least 10 cigarettes per day (CPD), as confirmed by saliva cotinine \>50 ng/ml and/or NicAlert=6)
• Age: \>= 21 years old to \<= 70 years old
• Willingness to use a non-menthol e-cigarette only (until menthol flavored SREC becomes available)
• Willingness to abstain from marijuana for the duration of the study

You may not qualify if:

• Unstable medical conditions (such as unstable heart disease, seizures, cancer, uncontrolled thyroid disease, diabetes, Hepatitis B or C or renal or liver impairment, glaucoma, history of stroke, an ulcer in the past year, or active use of an inhaler for Asthma or Chronic obstructive pulmonary disease (COPD).
• Psychiatric medications with the exception of Selective Serotonin Reuptake Inhibitors (SSRI) and Serotonin and norepinephrine reuptake inhibitors (SNRIs) and current evaluation by the study physician that the participant is otherwise healthy, stable and able to participate.
• Pregnancy or breastfeeding (by history and pregnancy test); women of childbearing potential must be using an acceptable method of contraception
• 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 \[no more than 15 times in combination in the past month and must agree to abstain from their use during the period of the study.\]
• Concurrent use of nicotine-containing medications
• 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 ok). Must not be on opioid replacement therapy.
• Medications: Use of medications that are inducers of nicotine metabolizing enzyme CYP2A6 (Example: rifampicin, dexamethasone, phenobarbital, and other anticonvulsant drugs). Use of medications for cardiovascular conditions including hypertension (Example: beta- and alpha-blocking drugs). Use of stimulants (Example: Adderall)
• Other/Misc Health Conditions: Oral thrush; fainting within the last 30 days; untreated thyroid disease; other "life threatening illnesses" as per study physician's discretion.
• Concurrent participation in another clinical trial
• Inability to read and write in English
• Planning to quit smoking or vaping within the next 60 days
• A known propylene glycol/vegetable glycerin allergy

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

UCSF Tobacco Research Center

San Francisco, California, 94110, United States

Location

MeSH Terms

Conditions

Tobacco Use Disorder; Vaping

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Smoking; Behavior

Study Officials

• Neal L. Benowitz, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2018
• First Posted: March 22, 2018
• Study Start: August 1, 2022
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: December 9, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)