Effects of Oral Nicotine and Caffeine Pouches on Anaerobic Performance, Autonomic Function, Cognition, and Behavior

The goal of this randomized placebo controlled crossover trial is to determine effects of oral nicotine and caffeine pouches on anaerobic performance, autonomic function, cognition, and behavior in adult non-obese adult male volunteers between ages 21 and 40.

Accordingly, the primary aims of the study are to determine the effects of acute oral nicotine pouches, oral caffeine pouches, or both, on measures of

• anaerobic performance
• cognition
• cardiovascular and autonomic function
• appetite and food intake.

Researchers will compare oral nicotine pouches, oral caffeine pouches, both oral nicotine and caffeine pouches, and a flavor and color matched placebo to see if how they differentially affect measurements of

• physical performance,
• cognition,
• cardiovascular and autonomic function
• appetite and food intake.

On four separate occasions, participants will be asked to place the oral pouches in their mouth and complete several anerobic cycling, cognitive, and balance tests while blood and salivary biomarkers, subjective appetite ratings, and cardiovascular and autonomic function measurements are collected. After each trial, participants will complete a 24-hr food record.

Study Overview

• Status: Enrolling by invitation
• Conditions: Fatigue, Mental; Fatigue; Muscle, Heart
• Intervention / Treatment: Other: Oral Pouch - Nicotine; Other: Oral Pouch - Caffeine; Other: Oral Pouch - Placebo

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

Contacts and Locations

Study Locations

• United States
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39406
      • University of Southern Mississippi - School of Kinesiology and Nutrition

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Being 21 to 40 years of age
• Being biologically male
• Having a body mass index (BMI) of < 30 kilograms/meter-squared
• Participating in moderate/vigorous exercise for at least 150 minutes/week over the last month

Exclusion Criteria:

• individuals who are younger than 21 or older than 40
• missing any limbs or part of a limb
• having any neuromuscular/musculoskeletal injury or impairment that would prevent performing any exercise/functional measures for this study
• having a pacemaker or any other electrical implant
• a diagnosis (defined as the presence of disease of or using medication to treat the disease) of heart failure, cardiomyopathy (dilated or hypertrophic), valvular disease, type I or type II diabetes
• taking insulin injections
• any history of severe or mild traumatic brain injury within the last two years
• kidney, liver, thyroid, or heart disease
• treated or untreated American Heart Association stage 2 hypertension (>140 millimeters of mercury / > 90 millimeters of mercury)
• any diagnosed neurological or neurodegenerative diseases
• having donated blood or plasma in the last 20 days prior to blood collection procedures
• taking any supplements/medications that may interfere with the results of the study
• any surgeries that would impact swallowing and/or digestion
• currently smoking, vaping, using e-cigarettes, or using any other combustible/smokeless tobacco products
• using smokeless tobacco-free nicotine products on more than 2 days/week
• daily caffeine use of more than 250 milligrams/day or use of any oral caffeine pouches
• have allergies or are regularly taking medications that would impact this study and/or negatively interact with caffeine or nicotine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral Nicotine Pouches; Single dose 3mg oral nicotine pouch	Other: Oral Pouch - Nicotine; Ingestion of a randomized oral nicotine pouch
Experimental: Oral Caffeine Pouches; Single dose 100mg oral caffeine pouch	Other: Oral Pouch - Caffeine; Ingestion of a randomized oral caffeine pouch
Experimental: Combination of oral nicotine and caffeine pouches; Single simultaneous doses of a 3mg oral nicotine pouch and a 100mg oral caffeine pouch	Other: Oral Pouch - Nicotine; Ingestion of a randomized oral nicotine pouch; Other: Oral Pouch - Caffeine; Ingestion of a randomized oral caffeine pouch
Placebo Comparator: Placebo; Flavor, color, and appearance matched placebo	Other: Oral Pouch - Placebo; Ingestion of a randomized oral placebo pouch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wingate Anaerobic Cycling Test	Changes in anaerobic cycling power output	Baseline, 15, 16, 19, 20, 23, 24, 27, 28, 31, 32, and 60 minutes post-ingestion
Concentration of blood lactate	Changes in blood lactate concentration from capillary blood	Baseline, 25, 32 minutes post-ingestion
Concentration of salivary cortisol	Changes in salivary cortisol concentration from saliva	Baseline, 15, 25, 32 minutes post-ingestion
Concentration of salivary interleukin-6	Changes in interleukin-6 concentration from saliva	Baseline, 15, 25, 32 minutes post-ingestion
Salivary catecholamine concentration	Changes in salivary catecholamine concentration from saliva	Baseline, 15, 27, 40 minutes post-ingestion
Profile of Mood States	Changes in Profile of Mood States scores (Score range: 0-60)	Baseline, 15, 32 minutes post-ingestion
Balance	Changes in standing postural sway	Baseline, 15, 32 minutes post-ingestion
Ratings of perceived exertion	Changes in ratings of perceived exertion (Scale range: 6-20 - lower ratings means less effort))	Baseline, 15, 16, 19, 20, 23, 24, 27, 28, 31, 32, and 60 minutes post-ingestion
Hunger - Visual Digital Analog Scale (0-100)	Changes in subjective ratings of hunger	Baseline, 15, 25, 32 minutes post-ingestion
Desire to eat - Visual Digital Analog Scale (0-100)	Changes in subjective ratings of desire to eat	Baseline, 15, 25, 32, 60 minutes post-ingestion
Prospective Consumption of Food - Visual Digital Analog Scale (0-100)	Changes in subjective ratings of prospective consumption of food	Baseline, 15, 25, 32, 60 minutes post-ingestion
Fullness - Visual Digital Analog Scale (0-100)	Changes in subjective ratings of fullness	Baseline, 15, 25, 32, 60 minutes post-ingestion
Food Intake - Digital 24-hour food record	Consumption of food and beverage after study visit	24 hours following the end of each visit
Blood Pressure	Absolute brachial blood pressure values (systolic and diastolic) and relative changes from baseline.	Baseline, 15, 19, 23, 27, 31, and 60 minutes post-ingestion
Heart Rate	Absolute heart rate values and relative changes from baseline.	Baseline, 15, 19, 23, 27, 31, and 60 minutes post-ingestion
Trail Making Test - Digital Cognitive Function Test	Changes in trail making test scores	Baseline, 15, 32 minutes post-ingestion
Sustained Attention Test - Digital Cognitive Function Test	Changes in sustained attention test scores	Baseline, 15, 32 minutes post-ingestion
Visual Working Memory Span Test - Digital Cognitive Function Test	Changes in visual working memory span test scores	Baseline, 15, 32 minutes post-ingestion
Stroop Test - Digital Cognitive Function Test	Changes in Stroop test scores	Baseline, 15, 32 minutes post-ingestion
Deary-Liewald Test - Digital Cognitive Function Test	Changes in Deary-Liewald test scores	Baseline, 15, 32 minutes post-ingestion
Cerebral Blood flow	Doppler ultrasound derived blood flow in the carotid artery	Baseline, 15, 19, 23, 27, and 31 minutes post-ingestion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Glucose Concentration	Changes in blood glucose concentration from capillary blood	Baseline, 15, 25, 32 minutes post-ingestion
Salivary insulin concentration	Changes in salivary insulin concentration from saliva	Baseline, 15, 25, and 32 minutes post-ingestion
Prefrontal Cortex Oxygenation	Near-infrared spectroscopy	Baseline, 15, 19, 23, 27, and 31 minutes post-ingestion
Peripheral Vascular Conductance	Blood flow in the brachial artery normalized to blood pressure (mL/min/mmHg)	Baseline, 15, 19, 23, 27, and 31 minutes post-ingestion
Electromyography	Electromyographic reading of muscle activity of the active muscles (glutes, hamstrings, quadriceps, and calves)	Baseline, 15, 16, 19, 20, 23, 24, 27, 28, 31, and 32 minutes post-ingestion
Peripheral Blood Flow	Doppler ultrasound derived blood flow in the brachial artery	Baseline, 15, 19, 23, 27, and 31 minutes post-ingestion

Collaborators and Investigators

• Sponsor: University of Southern Mississippi
• Investigators: Principal Investigator: Austin J Graybeal, PhD, University of Southern Mississippi

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: July 19, 2024
• First Submitted That Met QC Criteria: July 25, 2024
• First Posted (Actual): July 31, 2024

Study Record Updates

• Last Update Posted (Actual): August 2, 2024
• Last Update Submitted That Met QC Criteria: July 31, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Fatigue; Mental Fatigue; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Nicotine; Caffeine
• Other Study ID Numbers: 24-0285

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