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Effects of Breathing Training and Nitrate on Exercise at Simulated Altitude

E

Embry-Riddle Aeronautical University

Status

Enrolling

Conditions

Exercise Training
Healthy Adults
Mechanical Ventilation Dependence
Inspiratory Muscle Training
Hypoxia
Nitrate Supplementation
Exercise Intolerance
Dietary Supplement

Treatments

Device: Sham Respiratory Muscle Training
Dietary Supplement: Dietary Supplement: Beetroot Juice Concentrate
Device: Respiratory Muscle Training (RMT)
Dietary Supplement: placebo beverage

Study type

Interventional

Funder types

Other

Identifiers

NCT07216755
1R15HL173855-01A1 (U.S. NIH Grant/Contract)
25-077

Details and patient eligibility

About

This study investigates whether respiratory muscle training (RMT) and dietary nitrate supplementation can improve exercise tolerance under simulated moderate altitude conditions. Exposure to reduced oxygen availability at altitude places additional strain on the cardiovascular and respiratory systems, which may limit endurance performance. By combining RMT-designed to strengthen the muscles involved in breathing-with nitrate therapy, which enhances nitric oxide availability and vascular function, this study aims to determine whether these interventions independently or synergistically improve oxygen delivery, reduce physiological strain, and enhance exercise performance. The findings will help identify non-pharmacological strategies to improve physical performance and tolerance to hypoxia in both clinical and operational environments.

Full description

This study is designed to test whether two non-drug interventions-respiratory muscle training (RMT) and dietary nitrate supplementation-can improve exercise performance and tolerance when oxygen levels are lower than normal, such as at moderate altitude.

When people exercise in low-oxygen environments, the body must work harder to deliver enough oxygen to the muscles. This can lead to faster fatigue and reduced endurance. Strengthening the breathing muscles and improving blood vessel function may help the body adapt better to these conditions. This study will explore how RMT and nitrate supplementation, either alone or together, affect breathing, blood flow, and exercise capacity.

Why This Study Is Being Done:

Researchers want to find out whether strengthening the breathing muscles through RMT, and increasing nitric oxide in the body through nitrate (found naturally in beetroot juice), can make it easier to exercise when oxygen is limited. Nitric oxide helps widen blood vessels and improve oxygen delivery to muscles. The goal is to learn if these approaches can help healthy adults perform better in low-oxygen conditions and whether combining them produces a greater benefit than using either one alone.

Who Will Participate:

Healthy, recreationally active adults will take part in this study. Participants will not have any known heart, lung, or metabolic disease. They will be randomly assigned to one of four groups:

Breathing training plus nitrate supplement

Breathing training plus placebo

Sham (fake) breathing training plus nitrate supplement

Sham (fake) breathing training plus placebo

What Participants Will Do:

Each participant will complete testing before and after a 4- to 6-week intervention period. During the intervention:

Participants in the RMT group will use a handheld breathing trainer several times per week to strengthen their breathing muscles.

Participants in the nitrate group will drink a small amount of concentrated beetroot juice daily.

Those in the sham groups will use a very low-resistance breathing device or a placebo drink that looks and tastes the same but contains no nitrate.

Before and after training, participants will perform exercise tests on a stationary bicycle both at normal oxygen levels and at simulated altitude inside a controlled environmental chamber. Testing will measure:

How long participants can exercise before becoming fatigued.

Oxygen use (VO₂), heart rate, breathing, and blood pressure during exercise.

Breathing muscle strength and endurance.

Oxygen levels in the blood and muscles.

Study Goals and Measurements:

Researchers will compare how exercise performance and physiological responses change with each treatment. The main goal is to see whether RMT and nitrate supplementation increase exercise tolerance at simulated altitude. Secondary goals include understanding how these interventions affect breathing patterns, oxygen use efficiency, and cardiovascular function during exercise.

Why This Study Matters:

This research will help scientists and health professionals understand how to improve physical performance and resilience when oxygen is limited. The findings could be useful for:

Pilots, military personnel, and athletes who train or work at altitude.

Patients with conditions that make breathing or exercise difficult, such as heart or lung disease.

Future spaceflight or aerospace medicine applications, where oxygen availability can vary.

Safety and Ethics:

All participants will give written informed consent before joining the study. The study has been reviewed and approved by the Institutional Review Board for the Protection of Human Subjects in Research at Embry-Riddle Aeronautical University. All research procedures will follow the ethical principles outlined in the Declaration of Helsinki.

Expected Impact:

The results will show whether combining breathing training with nitrate supplementation can serve as a simple, non-pharmacological strategy to improve tolerance to low-oxygen environments. This could lead to better performance strategies for athletes, aviators, and others who face hypoxic or high-altitude conditions, as well as inform clinical approaches for patients who struggle with exercise intolerance.

Enrollment

80 estimated patients

Sex

All

Ages

18 to 40 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

  • Healthy adults between 18 and 40 years old.

Recreationally active (performing ≥3 hours of structured physical activity per week).

Non-smokers for at least the past 6 months.

Free from any known cardiovascular, pulmonary, metabolic, or neuromuscular disease as determined by health screening questionnaire and medical history.

Able to perform cycle ergometer exercise to volitional fatigue.

Willing to abstain from high-nitrate foods and supplements (e.g., beets, spinach, arugula) for 48 hours prior to each testing session.

Able and willing to provide written informed consent and comply with all study procedures.

Exclusion criteria

  • Diagnosis of or history of heart disease, hypertension, diabetes, or chronic respiratory disorders (e.g., asthma, COPD).

Current use of medications or supplements known to affect cardiovascular, metabolic, or respiratory function (e.g., beta-blockers, nitrates, stimulants).

Smoking, vaping, or tobacco use within the past 6 months.

Known allergy or intolerance to beetroot products or nitrates.

Participation in another interventional research study within the past 30 days.

Pregnant or breastfeeding women.

Any orthopedic or musculoskeletal limitation preventing safe exercise testing.

Failure to meet inclusion criteria or inability to complete familiarization and baseline testing.

Trial design

Primary purpose

Basic Science

Allocation

Randomized

Interventional model

Factorial Assignment

Masking

Quadruple Blind

80 participants in 4 patient groups, including a placebo group

RMT + Nitrate Supplementation
Experimental group
Description:
Participants complete a multi-week respiratory muscle training (RMT) program using a handheld breathing device that provides progressive inspiratory and expiratory resistance. Participants also consume a daily standardized dose of beetroot juice concentrate containing dietary nitrate. This combination is expected to enhance breathing muscle strength, vascular function, and exercise tolerance under simulated altitude.
Treatment:
Device: Respiratory Muscle Training (RMT)
Dietary Supplement: Dietary Supplement: Beetroot Juice Concentrate
Respiratory Muscle Training + Placebo
Placebo Comparator group
Description:
Participants perform the same RMT program as in Arm 1 but consume a placebo beverage that is visually and taste-matched to the nitrate drink but contains no active nitrate. This group allows assessment of the independent effects of respiratory muscle training.
Treatment:
Dietary Supplement: placebo beverage
Device: Respiratory Muscle Training (RMT)
Sham Respiratory Muscle Training + Nitrate Supplementation
Sham Comparator group
Description:
Participants perform sham RMT with a very low resistance load that does not provide a training stimulus, while consuming the active nitrate beverage daily. This group isolates the independent effect of nitrate supplementation on exercise tolerance under hypoxic conditions.
Treatment:
Dietary Supplement: Dietary Supplement: Beetroot Juice Concentrate
Device: Sham Respiratory Muscle Training
Sham Respiratory Muscle Training + Placebo
Placebo Comparator group
Description:
Participants complete sham RMT with minimal breathing resistance and consume a placebo beverage identical in appearance and flavor to the nitrate supplement but containing no active ingredients. This serves as the control condition for comparison with all other intervention groups.
Treatment:
Dietary Supplement: placebo beverage
Device: Sham Respiratory Muscle Training

Trial contacts and locations

1

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Central trial contact

Scott Ferguson K Ferguson, Ph.D.

Data sourced from clinicaltrials.gov

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