Cigarette Harm Reduction With Electronic Cigarette Use

NCT ID: NCT03473483

Last Updated: 2022-12-09

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-01
• Study Completion Date: 2026-03-31

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.

Conditions

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

Keywords

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

SREC only or cigarette only use

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.

Group Type: EXPERIMENTAL

SREC

Intervention Type: 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

Alternate product from Arm 1

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.

Group Type: EXPERIMENTAL

SREC

Intervention Type: 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

Standardized Dual Use

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.

Group Type: EXPERIMENTAL

SREC

Intervention Type: 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

Interventions

SREC

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

Intervention Type: OTHER

Other Intervention Names

Standardized Research E-Cigarette

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Neal L. Benowitz, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

UCSF Tobacco Research Center

San Francisco, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

U01DA045519

Identifier Type: NIH

Identifier Source: secondary_id

View Link

17-23142

Identifier Type: -

Identifier Source: org_study_id