Influence of Graded Hypercapnia on Endurance Exercise Performance

Study Overview
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Brief Summary
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The aim of this randomized, single-blind, placebo-controlled crossover trial is to determine the effects of graded hypercapnia (0, 2, and 4% inspired CO2) on endurance performance. Twelve healthy and fit young adults (men and women) will complete this study. Participants will perform experimental trials on 3 separate days (one each breathing 0%, 2%, and 4% inspired CO2-all with normal 21% oxygen). During each trial, they will perform 10 minutes of submaximal treadmill walking exercise and then complete a self-paced 2-mile treadmill run time-trial.

Detailed Description
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Participants will undergo baseline measurements of pulmonary function and maximal oxygen uptake (VO2max). They will then complete two familiarization trials, with 10 minutes of submaximal exercise ( 40%VO2max) followed by a self-paced 2-mile treadmill time trial. Lastly, they will complete three experimental trials, repeating the same submaximal and time-trial exercise procedures while breathing the test gas (0%, 2%, or 4% CO2-all with normal 21% oxygen). During the experimental trials, arterialized capillary blood samples will be collected at rest breathing room air, at rest breathing the test gas, and during submaximal exercise at 40% VO2max breathing the test gas. The primary outcome is 2-mile treadmill time-trial performance. Secondary outcomes include ventilation, metabolic rate, heart rate, arterialized capillary pH/PCO2/HCO3, perceived exertion, dyspnea, leg discomfort, breathing descriptors, and headache ratings.

Official Title
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Influence of Graded Hypercapnia on Endurance Exercise Performance

Conditions
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Hypercapnia

Intervention / Treatment
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* Other: Inspired gas


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age 18-45 In good health as determined by medical screening Passed his/her most recent Army Combat Fitness Test (ACFT) (Military Volunteers Only) or performs aerobic exercise at least 2 times per week and able to complete two mile run in ≤ 21 minutes (Civilian Volunteers) Willing to not participate in any exercise or drink alcoholic beverages for 24 hours before each study visit. Willing to not take part in any strenuous exercise in the 36 hours before each visit. Willing not to drink caffeine or eat food until after testing on familiarization and performance testing visits (visits 2-6). Willing to maintain a similar dietary pattern in the 2 days before each familiarization and performance visits. Have supervisor approval if permanent party military or a federal employee at U.S. Army Natick Soldier System Center Able to speak and read English fluently Exclusion Criteria: Females who are pregnant or planning to become pregnant during the study Taking dietary supplements, prescriptions, or over the counter medication, other than a contraceptive (unless approved by medical staff & PI) Musculoskeletal injuries that compromise ability to run on a treadmill Abnormal blood count, presence of abnormal blood chemicals (hemoglobin S or sickle cell traits) Smokers or tobacco/nicotine users (unless have quit > 1 month prior) Any history of asthma Current or recent respiratory tract or sinus infections (< 1 month prior) Allergy to skin adhesive Any history of migraine or recurrent headaches Any history of panic disorder Blood donation in the previous 8 weeks Positive Covid-19 test within the last month

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized, single-blinded crossover design
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 4% CO2<br>Inspired gas containing 4% CO2, 21% O2, balance N2 | Other: Inspired gas<br>* Inspired gas content<br>|
| Experimental: 2% CO2<br>Inspired gas containing 2% CO2, 21% O2, balance N2 | Other: Inspired gas<br>* Inspired gas content<br>|
| Sham Comparator: 0% CO2<br>Inspired gas containing 0% CO2, 21% O2, balance N2 | Other: Inspired gas<br>* Inspired gas content<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2 mile self-paced treadmill time trial performance | Time to complete self-paced 2 mile treadmill time trial (min:sec) | 30 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilation rate | Ventilation rate will be assessed using a pneumotachometer [L/min] | 30 minutes | 
| Oxygen consumption | Oxygen consumption will be assessed using computerized indirect calorimetry [ml/kg/min] | 30 minutes | 
| Heart rate | Heart rate will be assessed using telemetry [beats per min] | 30 minutes | 
| Arterialized capillary pH | Arterialized capillary pH will be assessed using a blood gas analyzer [Unitless] | 30 minutes | 
| Arterialized capillary pCO2 | Arterialized capillary pCO2 will be assessed using a blood gas analyzer [mmHg] | 30 minutes | 
| Arterialized capillary HCO3 | Arterialized capillary HCO3 will be assessed using a blood gas analyzer [mEq/L] | 30 minutes | 
| Rating of perceived exertion | Rating of perceived exertion will be assessed using Borg's 6-20 scale [AU] | 30 minutes | 
| Dyspnea | Rating of perceived dyspnea will be assessed using Borg's 0-10 scale [AU] | 30 minutes | 
| Leg discomfort | Rating of perceived leg discomfort will be assessed using Borg's 0-10 scale [AU] | 30 minutes | 
| Headache | Headache will be assessed using a visual analog scale [AU] | 30 minutes | 
| Breathing descriptors | Breathing descriptors will be assessed by having participants check statements that apply to their breathing (e.g., breathing out requires more effort) [unitless] | 30 minutes |