Concentration Impact Nicotine Salt (CINS)

Impact of the Nicotine Concentration on the Efficacy of a Nicotine Salt Vape Pod System as Smoking Cessation Tool

Double-blind (for the two active arms), randomized, three-arm (two active and one control) clinical trial investigating factors (e.g. nicotine concentration) influencing the success of smoking cessation strategies and possible health risks related to nicotine salt vaping.

Study Overview

• Status: Recruiting
• Conditions: Smoking Cessation; Vaping
• Intervention / Treatment: Procedure: Smoking cessation counseling; Other: Open system vape device and nicotine salt e-liquids

Detailed Description

At the clinic screening visit demographics, smoking (including the Fagerström Test for Cigarette Dependence (FTCD) Questionnaire) and medical history, concomitant medication, vital signs, body mass index (BMI) and exhaled carbon monoxide (CO) will be assessed, and a physical examination will be performed. Saliva samples will be collected for cotinine and nicotine metabolite ratio (NMR) measurement, urine samples for urinary anabasine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), nicotine metabolites, tobacco-specific nitrosamines (TSNA), and VOC, and blood samples for genotyping, steroid levels, blood lipids, creatinine, and glucose.

After randomization the open system vape device and the nicotine salt e-liquids will be distributed to the participants of the two active arms. Use of e-liquids in the active arms will be ad libitum during three months and will be monitored by returned empty e-liquid bottles.

All groups will receive smoking cessation counseling at baseline, week 1, and week 4. Visits at the center at baseline, week 4, and 3 months will include questionnaires regarding TC and EC use, respiratory symptoms, liking, and adverse events, measurement of heart rate, blood pressure, BMI, blood steroid levels, HDL, LDL, creatinine and glucose, and measurement of urinary TSNA, VOC and nicotine metabolites. For participants self-reporting TC abstinence, exhaled CO validation and urinary anabasine and NNAL will be collected to verify tobacco abstinence.

A follow-up visit also assessing TC abstinence will take place at 6 months.

• Study Type: Interventional
• Enrollment (Estimated): 312
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Evangelia Liakoni, MD; Phone Number: 0041316325461; Email: evangelia.liakoni@insel.ch

Study Locations

• Switzerland
  • Bern, Switzerland
    • Recruiting
    • Inselspital
    • Contact: Evangelia Liakoni, MD; Phone Number: +41 31 632 5461; Email: evangelia.liakoni@insel.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adult (≥ 18 years old) smokers (at least 5 TC per day for at least 12 months)
• Motivated to quit smoking as evidenced by signing the informed consent form at trial enrolment specifying that a target quit date will be set
• Exhaled CO ≥ 10 ppm or saliva cotinine of > 30 ng/ml (in case of borderline CO measurement of 6-10 ppm) at screening
• Willing to participate in the trial even if allocated to the control group
• Ability to communicate well with the investigator and to understand and comply with the requirements of the study
• Signed informed consent form

Exclusion Criteria:

• Known hypersensitivity/allergy to a content of the e-liquid
• Pregnancy or breast feeding
• Intention to become pregnant during the course of the study
• Current regular use of EC or tobacco heating systems
• Use of NRT, varenicline, or bupropion in the month prior to the screening visit
• People who smoke tobacco combined with marijuana and do not currently want to quit marijuana use
• Participation in an interventional trial within 30 days prior to the screening visit
• Legal incapacity or limited legal capacity at screening
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active arm, low concentration (18 mg/mL) nicotine salt e-liquids	Procedure: Smoking cessation counseling; Smoking cessation counseling at baseline, week 1, and week 4.; Other: Open system vape device and nicotine salt e-liquids; Ad libitum use of nicotine salt e-liquids during three months.
Active Comparator: Active arm, high concentration (59 mg/mL) nicotine salt e-liquids	Procedure: Smoking cessation counseling; Smoking cessation counseling at baseline, week 1, and week 4.; Other: Open system vape device and nicotine salt e-liquids; Ad libitum use of nicotine salt e-liquids during three months.
Other: Control group; Receive only smoking cessation counseling	Procedure: Smoking cessation counseling; Smoking cessation counseling at baseline, week 1, and week 4.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
7-day point prevalence tobacco abstinence (in terms of non-inferiority)	Defined as no smoking, i.e. "not a puff", self-reported and confirmed by exhaled carbon monoxide (<10 ppm) and urinary anabasine levels (<3 ng/mL) when using low vs. high nicotine salt concentration e-liquids.	1 month
Volume of e-liquid used (in terms of superiority)	Volume of e-liquid used when using low vs. high nicotine salt concentration e-liquids.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
7-day point prevalence tobacco cigarette abstinence	Same as primary outcome using a less strict definition of tobacco cigarette abstinence, i.e. self-report of smoking no more than 5 cigarettes	1 month
Continuous tobacco cigarette abstinence	Self-reported continuous abstinence at 1 month (confirmed by exhaled carbon monoxide and urinary anabasine) using the stricter, i.e. "not a puff" and the less strict, i.e. "no more than 5 cigarettes" definition	1 month
7-day point prevalence tobacco cigarette abstinence	Self-reported 7-day point prevalence abstinence at 3 and 6 months (confirmed by exhaled carbon monoxide and urinary anabasine) using the stricter, i.e. "not a puff" and the less strict, i.e. "no more than 5 cigarettes" definition	3 and 6 months
Continuous tobacco cigarette abstinence	Self-reported continuous abstinence at 3 and 6 months (confirmed by exhaled carbon monoxide and urinary anabasine) using the stricter, i.e. "not a puff" and the less strict, i.e. "no more than 5 cigarettes" definition, and when allowing a 2-week "grace period" from the target quit date	3 and 6 months
Number of drop-outs		Through study completion
Time of dropping out		Through study completion
Urinary volatile organic compounds (VOC)	Change of non-nicotine toxicants (VOC) from baseline to 1 month and 3 months of nicotine salt use	1 and 3 months
Tobacco-specific nitrosamines (TSNA)	Change of non-nicotine toxicants (TSNA) from baseline to 1 month and 3 months of nicotine salt use	1 and 3 months
Liking/rating of trial product (active arms)	Questions regarding helpfulness in refraining from smoking, how satisfying and how good the e-cigarette tastes compared to the tobacco cigarettes, if they would recommend the assigned trial product to another smoker, and any potential practical problems they might have with the handling.	1 and 3 months
Respiratory symptoms	Checklist with specific questions regarding shortness of breath, wheezing, cough or phlegm	Up to 6 months
Adverse events	Checklist with specific questions regarding presence or absence of nausea, sleep disturbance, throat/mouth irritation or other	Up to 6 months
Total nicotine amount vaped		1 and 3 months
Total volume of e-liquid consumed		1 and 3 months
Steroid profiles	Steroid profiles in saliva, blood and urine	Baseline, 1, 3 and 6 months
Number of cigarettes smoked per day among those who fail to quit		Through study completion

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Collaborators: Swiss National Science Foundation
• Investigators: Principal Investigator: Evangelia Liakoni, MD, Inselspital, Bern University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2024
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: January 13, 2021
• First Submitted That Met QC Criteria: January 22, 2021
• First Posted (Actual): January 27, 2021

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: 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: BASEC-ID: 2020-01875

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data that relates to individual, primary publications (and not the whole study database as such) will be deposited in the Bern Open Repository and Information System (BORIS). All efforts will be made to protect privacy and to de-identify the data. Data will be shared on request under the following conditions: A meaningful study question by the requester, outline of the planned analyses, valid methodology, signed data sharing agreement that contains a confidentiality agreement in case of sensitive data.

Drug and device information, study documents

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