Cardiovascular Effects of Very Low Nicotine Content Cigarettes (CEV)

The study is measuring Cardiovascular effects of very low nicotine content cigarettes on daily and non-daily smokers

Study Overview

• Status: Recruiting
• Conditions: Tobacco Use
• Intervention / Treatment: Other: usual brand of Cigarettes; Drug: SPECTRUM cigarettes

Detailed Description

The FDA is planning regulatory actions to limit nicotine levels in cigarettes as far as it is not reduced to zero. The strategy is designed to reduce the addictiveness of cigarettes. However, nicotine related effects of the cigarettes with reduced nicotine content on various body systems are largely unknown. Following formal implementation of the regulatory policy what cardiovascular effects of reduced nicotine cigarettes, also called very low nicotine content cigarettes (VLNCC) are expected to persist is important to determine. This study will determine the cardiovascular effects of VLNCC such as change in heart rate, autonomic functions and indices of ventricular repolarization in smokers. Participants will be asked to smoke two VLNCC and one normal nicotine content cigarette (NNCC) while we will be recording their electrocardiogram (ECG) to see a change in heart rate, heart rate variability and indices of ventricular repolarization.

• Study Type: Interventional
• Enrollment (Estimated): 49
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Maria Anwar, MS; Phone Number: 802-922-3343; Email: manwar@wakehealth.edu

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Wake Forest University Health Sciences
      • Contact: Maria Anwar, MS; Phone Number: 802-922-3343; Email: manwar@wakehealth.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Self-reported cigarette smoking at least once in the past 30 days
• ≥21 years old
• Willingness to smoke research cigarettes or usual brand cigarettes during lab visit.
• Ability to speak, comprehend, and read English sufficiently to complete study procedures

Exclusion Criteria:

• Self-reported diagnosis of cardiovascular diseases like coronary artery disease, stroke, peripheral artery disease, cardiac arrhythmia, pulmonary embolism & blood clots in legs and arm in the past 3 months
• Body temperature ≥ 100.4˙F
• Unstable health conditions interfering with electrocardiogram (ECG) measurements
• Self-reported diagnosis of hyperthyroidism or thyrotoxicosis
• Currently pregnant (as indicated by urine pregnancy test at the start of laboratory visit) or breastfeeding.
• Currently seeking treatment to quit smoking

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Usual Brand of Cigarettes; Participants will smoke 2-3 cigarettes of their usual brand	Other: usual brand of Cigarettes; Usual Brand of Cigarettes
Experimental: Research Cigarettes (SPECTRUM); Participants will smoke 1-2 SPECTRUM cigarettes	Drug: SPECTRUM cigarettes; SPECTRUM cigarettes have varying amount of nicotine content; Other Names: Cigarette Smoke

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Heart rate - Very Low Nicotine Content Cigarettes (VLNCC)s - NRC102/103(0.5mg nicotine)	Change in heart rate from pre-exposure to post-exposure for the Very Low Nicotine Content Cigarettes (VLNCC)s - NRC102/103(0.5mg nicotine)	Hour 1
Change in Heart rate - Very Low Nicotine Content Cigarettes (VLNCC)s - NRC301/302(2.4mg nicotine)	Change in heart rate from pre-exposure to post-exposure for the Very Low Nicotine Content Cigarettes (VLNCC)s - NRC301/302(2.4mg nicotine)	Hour 1
Change in Heart rate - Normal Nicotine Content Cigarettes (NNCC)s - NRC600/601(15.8mg nicotine)	Change in heart rate from pre-exposure to post-exposure for the normal nicotine content cigarettes (NNCC)s - NRC600/601(15.8mg nicotine)	Hour 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Heart rate variability(HRV) - Very Low Nicotine Content Cigarettes (VLNCC)s - NRC102/103(0.5mg nicotine)	Change in measures of heart rate variability (HF, LF, LF/HF, RMSSD = root mean square of standard deviation; SDNN = standard deviation of normal-to-normal intervals, Total power) from pre-exposure to post-exposure for the Very Low Nicotine Content Cigarettes (VLNCC)s	Hour 1
Change in Heart rate variability(HRV) - Very Low Nicotine Content Cigarettes (VLNCC)s - NRC301/302(2.4mg nicotine)	Change in measures of heart rate variability (HF, LF, LF/HF, RMSSD = root mean square of standard deviation; SDNN = standard deviation of normal-to-normal intervals, Total power) from pre-exposure to post-exposure for the Very Low Nicotine Content Cigarettes (VLNCC)s	Hour 1
Change in Heart rate variability(HRV) - Normal Nicotine Content Cigarettes (NNCC)s - NRC600/601(15.8mg nicotine)	Change in measures of heart rate variability (HF, LF, LF/HF, RMSSD = root mean square of standard deviation; SDNN = standard deviation of normal-to-normal intervals, Total power) from pre-exposure to post-exposure for the Normal Nicotine Content Cigarettes (NNCC)s	Hour 1
Change in electrocardiogram (ECG) Measures - Very Low Nicotine Content Cigarettes (VLNCC)s - NRC102/103(0.5mg nicotine)	Measures of ventricular repolarization (Q-T interval, QTc, Tp-e interval)from pre-exposure to post-exposure for the Very Low Nicotine Content Cigarettes (VLNCC)s	Hour 1
Change in electrocardiogram (ECG) Measures - Very Low Nicotine Content Cigarettes (VLNCC)s - NRC300/301(2.4mg nicotine)	Measures of ventricular repolarization (Q-T interval, QTc, Tp-e interval)from pre-exposure to post-exposure for the Very Low Nicotine Content Cigarettes (VLNCC) s	Hour 1
Change in electrocardiogram (ECG) Measures - Normal Nicotine Content Cigarettes (NNCC)s - NRC600/601(15.8mg nicotine)	Measures of ventricular repolarization (Q-T interval, QTc, Tp-e interval)from pre-exposure to post-exposure for the Normal Nicotine Content Cigarettes (NNCC)s	Hour 1

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Investigators: Principal Investigator: Eric C Donny, PhD, Wake Forest University Health Sciences

Publications and helpful links

General Publications

• Benowitz NL, Henningfield JE. Establishing a nicotine threshold for addiction. The implications for tobacco regulation. N Engl J Med. 1994 Jul 14;331(2):123-5. doi: 10.1056/NEJM199407143310212. No abstract available.
• Benowitz NL, Henningfield JE. Reducing the nicotine content to make cigarettes less addictive. Tob Control. 2013 May;22 Suppl 1(Suppl 1):i14-7. doi: 10.1136/tobaccocontrol-2012-050860.
• Hatsukami DK, Kotlyar M, Hertsgaard LA, Zhang Y, Carmella SG, Jensen JA, Allen SS, Shields PG, Murphy SE, Stepanov I, Hecht SS. Reduced nicotine content cigarettes: effects on toxicant exposure, dependence and cessation. Addiction. 2010 Feb;105(2):343-55. doi: 10.1111/j.1360-0443.2009.02780.x.
• Tachmes L, Fernandez RJ, Sackner MA. Hemodynamic effects of smoking cigarettes of high and low nicotine content. Chest. 1978 Sep;74(3):243-6. doi: 10.1378/chest.74.3.243.
• Moheimani RS, Bhetraratana M, Peters KM, Yang BK, Yin F, Gornbein J, Araujo JA, Middlekauff HR. Sympathomimetic Effects of Acute E-Cigarette Use: Role of Nicotine and Non-Nicotine Constituents. J Am Heart Assoc. 2017 Sep 20;6(9):e006579. doi: 10.1161/JAHA.117.006579.

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 23, 2023
• First Submitted That Met QC Criteria: January 31, 2023
• First Posted (Actual): February 1, 2023

Study Record Updates

• Last Update Posted (Estimated): October 3, 2025
• Last Update Submitted That Met QC Criteria: September 29, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Cigarette smoking; Nicotine Content; Cardiovascular Disorders
• Additional Relevant MeSH Terms: Behavior; Smoking; Tobacco Smoking; Cardiovascular Diseases; Cigarette Smoking; Tobacco Use
• Other Study ID Numbers: IRB00092813

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No