Cigarette Harm Reduction With Electronic Cigarette Use

Study Overview
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Brief Summary
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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
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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.

Official Title
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Cigarette Harm Reduction With Electronic Cigarette Use

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

Intervention / Treatment
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* Other: SREC


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SREC only or cigarette only use<br>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<br>* 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<br>* Other names: Standardized Research E-Cigarette;|
| Experimental: Alternate product from Arm 1<br>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<br>* 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<br>* Other names: Standardized Research E-Cigarette;|
| Experimental: Standardized Dual Use<br>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<br>* 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<br>* Other names: Standardized Research E-Cigarette;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in mean circadian heart rate | Compare changes in mean circadian heart rate between SREC-only and TC-only use | Baseline through study completion, approximately 2 years | 
| Changes in mean blood pressure | Compare changes in blood pressure between SREC-only and TC-only use | Baseline through study completion, approximately 2 years | 
| Changes in mean urinary catecholamine | Compare mean urinary catecholamine excretion between SREC-only and TC-only use | Baseline through study completion, approximately 2 years | 
| Mean Level of exposure to Tobacco smoke toxicant | Compare levels of exposure of tobacco smoke toxicant between dual SREC-TC use and TC-only use | Baseline through study completion, approximately 2 years | 
| Sensitivity of anabasine or nicotelline to nicotine metabolites | Sensitivity is defined as the ratio of anabasine or nicotelline to nicotine metabolites (cotinine or total nicotine equivalents) in urine from SREC-only and TC-only use. | Baseline through study completion, approximately 2 years | 
| Specificity of anabasine or nicotelline to nicotine metabolites | Specificity of anabasine or nicotelline will be compared to nicotine metabolites (cotinine or total nicotine equivalents) in urine from SREC-only and TC-only use. | Baseline through study completion, approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nicotine, tobacco, research electronic cigarette, e-cigarette, SREC