Clinical trial NCT03473483: Cigarette Harm Reduction With Electronic Cigarette Use
Official title: Cigarette Harm Reduction With Electronic Cigarette Use
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Nicotine Dependence
Tobacco Toxicity
Nicotine Dependence, Cigarettes
Cardiovascular Risk Factor
Nicotine Withdrawal
Keywords: nicotine
tobacco
research electronic cigarette
e-cigarette
SREC
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute on Drug Abuse (NIDA)
First posted: 2018-03-22
Enrollment: 0
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 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.

Detailed description: Daily cigarette smokers who are familiar with e-cigarette (EC) use will be instructed to use only NIDA Standardized Research Electronic Cigarettes (SREC) and tobacco cigarettes (TC) while enrolled on the study. Our overall goals are two-fold: (1) to compare nicotine and toxicant exposure and pharmacological effects of SREC used alone vs tobacco cigarettes alone (TC), or dual use; and (2) using SREC alone, TC alone, or ad libitum SREC use combined with 50% reduction in usual TC use as a model for dual use, to examine the extent to which nicotine and toxicant exposure and biomarkers of potential harm compare among the 3 groups. The former would inform the effects of total switching, the latter would inform the potential harm reducing effects of smoking fewer TC while using EC.

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)
* - 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

Exclusion Criteria:

* 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 conditions (such as current or past schizophrenia and/or current or past bipolar disorder, major personality disorder, or major depression current or within the past year. Participants with current or past minor to moderate depression and/or anxiety disorders will be reviewed by the study physician and considered for inclusion. Psychiatric hospitalizations are not exclusionary, but study participation will be determined as per study physician's approval.
* 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

Primary outcomes:
measure: Peak Nicotine Concentration
timeFrame: Up to 2 years
measure: Time of Peak Nicotine Concentration
timeFrame: Up to 2 years
measure: Mean overall systemic nicotine exposure
timeFrame: Baseline through study completion, approximately 2 years
measure: Change in Mean score on the Modified Cigarette Evaluation Questionnaire (mCEQ)
timeFrame: Baseline through study completion, approximately 2 years
measure: Patterns of puffing
timeFrame: Baseline through study completion, approximately 2 years
measure: Change in Mean score on the Minnesota Tobacco Withdrawal Scale-Revised (MTWS-R)
timeFrame: Baseline through study completion, approximately 2 years
measure: Change in Mean score on the Questionnaire on Smoking Urges (QSU-Brief)
timeFrame: Baseline through study completion, approximately 2 years
measure: Change in Mean score on the Positive and Negative Affect Scale (PANAS)
timeFrame: Baseline through study completion, approximately 2 years
Secondary outcomes:
measure: Changes in mean circadian heart rate
timeFrame: Baseline through study completion, approximately 2 years
measure: Changes in mean blood pressure
timeFrame: Baseline through study completion, approximately 2 years
measure: Changes in mean urinary catecholamine
timeFrame: Baseline through study completion, approximately 2 years
measure: Mean Level of exposure to Tobacco smoke toxicant
timeFrame: Baseline through study completion, approximately 2 years
measure: Sensitivity of anabasine or nicotelline to nicotine metabolites
timeFrame: Baseline through study completion, approximately 2 years
measure: Specificity of anabasine or nicotelline to nicotine metabolites
timeFrame: Baseline through study completion, approximately 2 years
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Tobacco Research Center
state: California
Study officials:
affiliation: University of California, San Francisco
name: Neal L. Benowitz, MD
role: PRINCIPAL_INVESTIGATOR
References: