Influence of Caffeine on Psychomotor Vigilance and Carbon Dioxide Tolerance During Graded Hypercapnia (C3F)

The aim of this randomized, double-blind, placebo-controlled crossover trial is to determine the effects of caffeine vs. placebo on psychomotor vigilance and carbon dioxide tolerance during graded hypercapnia.

Study Overview

• Status: Completed
• Conditions: Hypercapnia
• Intervention / Treatment: Other: Graded hypercapnia; Drug: Placebo; Drug: Caffeine

Detailed Description

Healthy and fit young adults (men and women) will participate in this study. Participants will perform two primary experimental trials on separate days, one after consuming 400 mg caffeine, and the other after consuming a non-caffeinated placebo. During each trial, participants will breathe increasing levels of inspired CO2 in a stepwise manner (0%, 2%, 4%, 6%, 8% CO2; all with 21% oxygen) during successive 12-minute stages. The endpoints of the graded hypercapnia protocol will be completion of the 8% CO2 stage, voluntary subject termination due to discomfort, or end-tidal CO2 greater than 70 mmHg. The investigators hypothesize that, compared to placebo, caffeine will lower end tidal and arterialized PCO2 and mitigate CO2-mediated decrements in psychomotor vigilance.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Natick, Massachusetts, United States, 01760
      • US Army Research Institute of Environmental Medicine

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female, age 18-45
• Body mass index 18.5-30.0 kg m-2
• Body mass 50-100 kg
• In good health as determined by the Office of Medical Support & Oversight (OMSO) General Medical Clearance
• Perform exercise at least 2 times per week
• Willing to abstain from exercise and alcoholic beverages for 24 hours before each study visit.
• Willing to abstain from caffeine for 12 hours prior to all study visits
• Willing to abstain from caffeine for 12 hours after visits 3 and 4
• Willing to remain fasted (no food or fluid other than water) from lights out until after arrival at the laboratory the following morning on each study day (~10 hours)
• Have supervisor approval if permanent party military or a federal employee at U.S. Army Natick Soldier System Center

Exclusion Criteria:

• Females who are pregnant or planning to become pregnant during the study
• Females who are surgically sterile
• History of severe adverse reaction to caffeine (e.g., headache, dizziness, diarrhea, insomnia)
• Taking dietary supplements, prescriptions, or over the counter medication, other than a contraceptive (unless approved by OMSO & PI)
• Abnormal blood count (For example: hemoglobin (Hb) outside of the typical normal values reported by LabCorp in accordance with OMSO (Normal [Hb] Males = 12.6-17.7 g/dL; Females = 11.1-15.9 g/dL) or hematocrit (Hct) outside of the normal ranges (Normal Hct Males = 37.5-51.0%; Females = 34.0-46.6%) levels, presence of abnormal blood chemicals (hemoglobin S or sickle cell traits)
• Any history of pulmonary or cardiovascular disease
• Current diagnosis of asthma (childhood asthma with no recurrence in the last 5 years ok)
• Smokers or nicotine users (unless have quit >1 month prior)
• Current or recent respiratory tract or sinus infections (< 1 month prior)
• Current diagnosis of migraine or recurrent headaches (previous diagnosis with no recurrence in the last 5 years ok)
• Any history of seizures
• Any history of panic disorder
• Blood donation in the previous 8 weeks
• Positive Covid-19 test within the last month (based on self-report)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo (microcrystalline cellulose) capsule taken in a single dose 1 hour prior to graded hypercapnia	Other: Graded hypercapnia; Volunteers breathe 0%, 2%, 4%, 6%, and 8% CO2 (with 21% O2, balance nitrogen) for 12 minutes each; Drug: Placebo; Placebo (microcrystalline cellulose) capsule taken in a single dose 1 hour prior to graded hypercapnia
Experimental: Experimental; 400 mg caffeine capsule taken in a single dose 1 hour prior to graded hypercapnia	Other: Graded hypercapnia; Volunteers breathe 0%, 2%, 4%, 6%, and 8% CO2 (with 21% O2, balance nitrogen) for 12 minutes each; Drug: Caffeine; 400 mg caffeine capsule taken in a single dose 1 hour prior to graded hypercapnia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
End-tidal CO2	End-tidal CO2 (mmHg)	60 minutes
PVT Performance	Psychomotor vigilance (mean reaction time in s)	60 minutes
Carbon dioxide tolerance	Time spent in graded hypercapnia protocol (minutes)	60 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory Rate	Breaths per minute	60 minutes
Ventilation	Ventilation (L/min)	60 minutes
Tidal volume	Tidal volume (L)	60 minutes
Oxygen Consumption	Oxygen consumption (L/min)	60 minutes
Carbon dioxide release	Carbon dioxide release (L/min)	60 minutes
Heart Rate	Heart Rate (Beats per minute)	60 minutes
Blood Pressure	Blood pressure (mmHg)	60 minutes
Total Mood Disturbance	Profile of Mood States (AU); higher number is worse mood	60 minutes
Arterialized capillary pH	pH (unitless)	60 minutes
Arterialized capillary PCO2	Partial pressure of carbon dioxide (mmHg)	60 minutes
Arterialized capillary bicarbonate	Bicarbonate (mmol/L))	60 minutes
Dyspnea	Borg 0-10 Scale (higher number is more dyspnea)	60 minutes
Discomfort	Borg 0-10 Scale (higher number is more discomfort)	60 minutes
Headache	100mm visual analog scale (higher number is worse headache)	60 minutes
Plasma caffeine	Plasma caffeine (ug/mL)	60 minutes
Plasma theobromine	Plasma theobromine (ug/mL)	60 minutes
Plasma theophylline	Plasma theophylline (ug/mL)	60 minutes
Plasma paraxanthine	Plasma paraxanthine (ug/mL)	60 minutes

Collaborators and Investigators

• Sponsor: United States Army Research Institute of Environmental Medicine

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2023
• Primary Completion (Actual): September 17, 2024
• Study Completion (Actual): September 17, 2024

Study Registration Dates

• First Submitted: October 4, 2024
• First Submitted That Met QC Criteria: October 8, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: October 8, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Cognitive Function; Caffeine; Carbon dioxide
• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Hypercapnia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Caffeine
• Other Study ID Numbers: 23-05

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