E-cigarettes and Cardiovascular Function (ISME-NRT)

Impact on Cardiovascular Function in Smokers Making a Quit Attempt Using E-cigarettes Compared With Smokers Making a Quit Attempt With Prescription Nicotine-Replacement Therapy

The large current uptake of e-cigarettes (2.8 million U.K. users in 2016; 26), the continuous involvement of e-cigarettes (which potentially affects their contents as well), the uncertainty about their medium- and longer-term effects, and the need to promote smoking cessation as means of reducing Cardiovascular disease, dictate that more research is urgently needed. Research exploring the impact of e-cigarettes on cardiovascular function/ health has been requested by the European Parliament, the British Medical Association, regulatory agencies, clinicians and researchers, as there is currently no consensus within the smoking cessation community as to the potential impact of e-cigarettes. With e-cigarettes being successful in replacing traditional cigarettes (i.e. up to 42% within a month), such studies should not only be efficacy-focused, but should also explore the physiological effects of e-cigarettes, as preliminary work in the field is contrasting and limited, in both the acute- and longer-term timeframe. Furthermore, as e-cigarettes are not simple nicotine-based products, the general public, researchers and government agencies cannot rely on the existing research exploring the effects of nicotine on the cardio-vasculature (e.g. coronary and peripheral vasoconstriction, intravascular inflammation and deregulation of cardiac autonomic function as well as inhibition of microcirculation). Thus, the lack of direct evidence - which would clarify the degree of safety of e-cigarettes for the user's vascular system and determine their longer-term cardiovascular disease risk - increases the need for research in the field.

Such studies will supply in-depth information to service-users and policy-makers, especially as the recently-initiated U.K.'s "Medicines and Healthcare Products Regulatory Agency" validation of e-cigarettes will increase likelihood of their introduction in smoking cessation clinics.

This study will bridge the existing knowledge gap and inform the general public, the scientific and the smoking cessation community in respect to the physiological (e.g. cardiovascular health) and participants' experience of both nicotine-inclusive and nicotine-free, e-cigarettes (when combined with behavioural change support) and compare it against a currently NHS-applied smoking cessation pathway that combines Nicotine Replacement Therapy and behavioural change support. This will allow future research to advance and optimize the pharmacological treatment of tobacco and nicotine dependence, by taking into consideration the study's physiological and Health Economics' findings.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Smoking Cessation; Microcirculation; Macrocirculation
• Intervention / Treatment: Other: Electronic Cigarette and behavioural change support.; Other: Nicotine-Free Electronic Cigarette and behavioural change support.; Other: Nicotine Replacement Therapy and behavioural change support.

• Study Type: Interventional
• Enrollment (Actual): 248
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Yorkshire
    • Sheffield, Yorkshire, United Kingdom, S10 2BP
      • Sheffield Hallam University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• smokers (at least 10 cigarettes/ day for the past year)
• willing to attempt quit smoking by using the National Health Service smoking cessation services or via e-cigarette use.

Exclusion Criteria:

• Non-ambulant people and people with a recent (e.g. within 6 months) cardiovascular disease event (e.g. stroke, myocardial infarction) or cardiac surgery,
• people with insulin-controlled diabetes mellitus or with coexisting skin conditions, leg ulcers, vasculitis or deep venous occlusion (as these may affect their cardiovascular function),
• pregnant women,
• people who require major surgery (which will prevent them of taking part in the study)
• people who following referral to the smoking cessation services, are advised that Nicotine Replacement Therapy is not appropriate for them,
• people who are currently using e-cigarettes on a daily basis, or currently undertaking an attempt within a smoking cessation service,
• people who are judged to be unable or are unwilling to give informed consent.

The study team will assess prospective participants and will not include in the study those who appear too frail or have health problems (e.g. dementia, Alzheimer's etc.) that might prevent them of giving a conscious, informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Nicotine-inclusive e-cigarettes; Participants will receive e-cigarettes (nicotine-inclusive) combined with behavioural change support over a 3 month period.	Other: Electronic Cigarette and behavioural change support.; The nicotine strength of Group A (nicotine-inclusive e-cigarettes) cartridges will be 18 mg/ml of nicotine strength. All participants will receive up to 6 behavioural change support sessions over the 3-month intervention period.; Other Names: e-cigarette
EXPERIMENTAL: Nicotine-free e-cigarettes; Participants will receive e-cigarettes (nicotine-free) combined with behavioural change support over a 3 month period.	Other: Nicotine-Free Electronic Cigarette and behavioural change support.; Group B participants will receive nicotine-free cartridges for the period of the intervention. All participants will receive up to 6 behavioural change support sessions over the 3-month intervention period.; Other Names: Nicotine-free e-cigarette
ACTIVE_COMPARATOR: Nicotine Replacement Therapy (NRT); Participants will be referred to smoking cessation services where they will be expected to receive Nicotine Replacement Therapy combined with behavioural change support over a 3 month period.	Other: Nicotine Replacement Therapy and behavioural change support.; Group C participants will be referred to smoking cessation services where they will be expected to receive Nicotine Replacement Therapy and up to 6 behavioural change support sessions over the 3-month intervention period, as per current guidelines.; Other Names: NRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intervention effect on Flow-mediated dilatation (FMD) assessed via ultrasound (%FMD).	Macro-vascular function assessment.	6 months following quit day.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intervention effect on Flow-mediated dilatation assessed via ultrasound (%FMD).	Macro-vascular function assessment.	3 days and 3 months following quit day.
Intervention effect on Laser Doppler Flowmetry (Perfusion Units).	Micro-vascular function assessment.	3 days, 3 months and 6 months following quit day.
Intervention effect on Mean Arterial Pressure.	Mean arterial pressure assessment.	3 and 6 months following quit day.
Intervention effect on Total Cholesterol/LDL ratio.	Finger prick test (Total Cholesterol/LDL).	3 and 6 months following quit day.
Intervention effect on Cardiovascular disease risk-reduction (Q-Risk assessment score).	Q-risk assessment.	3 and 6 months following quit day.
Patient experiences' assessment (Interview).	Interview assessments of patient experiences.	3 months following quit day.
Health Economics (Cost Utility Analysis).	Health economic assessment of the intervention.	6 months following quit day.
Carbon Monoxide assessment	Carbon Monoxide assessment	3 days, 3 months and 6 months following quit day.
Mean Arterial Pressure	Mean arterial pressure assessments	3 days, 3 months and 6 months following quit day.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical activity assessment	Short Form (SF)- International Physical Activity Questionnaire (IPAQ)	3 months and 6 months following quit day.

Collaborators and Investigators

• Sponsor: Sheffield Hallam University
• Collaborators: King's College London; Heart Research U.K.; Help2Change
• Investigators: Principal Investigator: Markos Klonizakis, DPhil, Reader (Clinical Physiology)

Publications and helpful links

General Publications

• Klonizakis M, Gumber A, McIntosh E, Brose LS. Medium- and longer-term cardiovascular effects of e-cigarettes in adults making a stop-smoking attempt: a randomized controlled trial. BMC Med. 2022 Aug 16;20(1):276. doi: 10.1186/s12916-022-02451-9.
• Jones G, McIntosh E, Brose LS, Klonizakis M. Participant Experiences of a Quit Smoking Attempt Through Either Nicotine Replacement Therapy (NRT) Methods or the Use of an E-cigarette. J Addict Med. 2022 May-Jun 01;16(3):272-277. doi: 10.1097/ADM.0000000000000881.
• Klonizakis M, Crank H, Gumber A, Brose LS. Smokers making a quit attempt using e-cigarettes with or without nicotine or prescription nicotine replacement therapy: Impact on cardiovascular function (ISME-NRT) - a study protocol. BMC Public Health. 2017 Apr 4;17(1):293. doi: 10.1186/s12889-017-4206-y.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 24, 2017
• Primary Completion (ACTUAL): April 21, 2020
• Study Completion (ACTUAL): December 23, 2020

Study Registration Dates

• First Submitted: February 9, 2017
• First Submitted That Met QC Criteria: February 17, 2017
• First Posted (ACTUAL): February 23, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 12, 2021
• Last Update Submitted That Met QC Criteria: July 6, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Ultrasound; Nicotine Replacement Therapy; Electronic Cigarettes; Laser Doppler Flowmetry
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: HWB-2016-17-S&E-10

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No