Effect of Nicotine Pouches on The Underlying Normal Electrocardiogram (NICOTUNE)

Effect of Nicotine Pouches on The Underlying Normal Electrocardiogram A Double-Blinded, Placebo-Controlled Cross-over Study Exploring the Dose-Response Effects of Nicotine Pouches on Heart Rate and the Electrocardiogram ACRONYM: The NICOTUNE Study

Nicotine pouches (NPs) are increasingly being used by children, adolescents, and adults, and are often presented as a less harmful alternative to, for example, smoking. The ability to use these products discreetly (unlike smoking) makes them an attractive option for individuals who wish to avoid the stigma that smokers may sometimes experience.

Nicotine is a well-known addictive substance that affects many organ systems, including the heart and circulatory system. The amount of nicotine in NPs varies greatly, but the pouches can contain large amounts of nicotine compared to the content of a single cigarette. While many studies have previously examined the effects of smoking and other nicotine products on the heart and circulatory system, specific data on the effects of NPs on these same systems are rather limited.

In light of the above, the investigators have planned a study to investigate whether NPs affect the circulatory system and heart rate, assessed through electrocardiography (ECG) and vital signs (i.e., pulse, blood pressure, respiratory rate, and more).

The investigators hypothesis is that the nicotine content in NPs leads to notable changes in the aforementioned measurements and could therefore potentially be associated with an increased health risk.

Study Overview

• Status: Completed
• Conditions: Heart Rate; Vital Sign Monitoring; Symptoms; ECG
• Intervention / Treatment: Other: Placebo Pouch; Other: Low Dose Nicotine Pouch; Other: High-dose Nicotine Pouch

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Hvidovre, Denmark, 2650
    • Department of cardiology, Copenhagen University Hospital, Amager & Hvidovre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adults aged 18-70 years.
• Regular (defined as daily) or occasional (generally defined as nondaily) nicotine users (e.g., cigarettes, vaping, or nicotine pouches).
• Willingness to abstain from nicotine, caffeine (including caffeine containing energy drinks), and alcohol for 6 hours prior to the session

Exclusion Criteria:

• History of cardiovascular conditions.
• Medications affecting cardiac conduction or autonomic function (e.g., antiarrhythmic drugs).
• Pregnancy or breastfeeding.
• Current illness or infection.
• History of substance abuse.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo pouch arm	Other: Placebo Pouch; A Placebo Pouch are placed and held in the oral cavity (between the gum and lip) for 20 minutes, as per standard use instructions. After 20 minutes pouches are removed from the oral cavity and disposed.
Experimental: Low-dosage nicotine pouch arm	Other: Low Dose Nicotine Pouch; A Low Dose Nicotine Pouch are placed and held in the oral cavity (between the gum and lip) for 20 minutes, as per standard use instructions. After 20 minutes pouches are removed from the oral cavity and disposed.
Experimental: High-dosage nicotine pouch arm	Other: High-dose Nicotine Pouch; A High Dose Nicotine Pouch are placed and held in the oral cavity (between the gum and lip) for 20 minutes, as per standard use instructions. After 20 minutes pouches are removed from the oral cavity and disposed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate	Changes in HR (beats/minute) obtained from an ECG recorded 20 minutes after nicotine pouch administration compared to the baseline ECG.	10 and 20 minutes (just before disposal) after the placement of the nicotine pouch in the oral cavity

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ECG parameters	Changes in various ECG parameters from baseline: • PR interval (msec) • QRS duration (msec) • QT interval (corrected, QTc) (msec) • HRV (msec)	10 and 20 minutes (just before disposal) after the placement of the nicotine pouch in the oral cavity
ST-T segment changes	ST-T segment changes, e.g., depression/elevation/inversion (mm) from baseline	10 and 20 minutes (just before disposal) after the placement of the nicotine pouch in the oral cavity
Arrhythmias	Any arrhythmias e.g., ectopic beats (yes/no, numerical) detected on the ECG compared with baseline ECG	10 and 20 minutes (just before disposal) after the placement of the nicotine pouch in the oral cavity

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure	Changes in Blood pressure (mmHg)	10 and 20 minutes (just before disposal) after the placement of the nicotine pouch in the oral cavity
Respiratory rate	Changes in Respiratory rate (breaths per minute)	10 and 20 minutes (just before disposal) after the placement of the nicotine pouch in the oral cavity
Oxygen saturation	Changes in Oxygen saturation (percentage/%)	10 and 20 minutes (just before disposal) after the placement of the nicotine pouch in the oral cavity
Body temperature	Changes in Body temperature (degree Celsius)	10 and 20 minutes (just before disposal) after the placement of the nicotine pouch in the oral cavity
Self-reported symptoms	Subjective symptoms self-reported by the participants during the intervention using VAS-questionnaire of 10 known nicotine effect/symptoms (nausea, dizziness, lightheadedness, nervousness, sweatiness, headache, excessive salivation, heart pounding, confusion, and weakness).	10 and 20 minutes (just before disposal) after the placement of the nicotine pouch in the oral cavity

Collaborators and Investigators

• Sponsor: Ekim Seven

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2025
• Primary Completion (Actual): October 31, 2025
• Study Completion (Actual): October 31, 2025

Study Registration Dates

• First Submitted: June 10, 2025
• First Submitted That Met QC Criteria: July 4, 2025
• First Posted (Actual): July 9, 2025

Study Record Updates

• Last Update Posted (Actual): December 11, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: H-25018523

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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