Hypoxic Breathing Safety Study for Healthy Volunteers

(MGH-nitrogen Trial)

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must not be taking: All medications

Disqualifiers: Pregnancy, Smoking, Diabetes, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

12 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to define the safety and the biochemical-physiological response of prolonged exposure to a normobaric low-oxygen environment in healthy volunteers.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any current medications, except for oral contraceptives, to participate in this study.

Is hypoxic breathing generally safe for humans?

A study involving fighter pilots found that hypoxic breathing, when combined with hyperventilation training, was well-tolerated and did not result in any adverse effects during a 24-hour follow-up. ^{1 2 3 4 5}

How does the treatment Inhaled Nitrogen differ from other treatments for hypoxia?

Inhaled Nitrogen is unique because it creates a controlled low-oxygen environment by reducing the oxygen concentration in the air you breathe, which is different from other treatments that might involve increasing oxygen levels. This approach is used to study how the body adapts to low oxygen conditions, unlike standard treatments that typically aim to increase oxygen availability. ^{1 6 7 8 9}

Research Team

Lorenzo Berra, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

Healthy adults aged 18-40 with a BMI of 19-24.9, able to consent and provide photo ID can join this trial. It's not for those born or living at high altitudes, heavy drinkers, pregnant women, smokers, or anyone with certain medical conditions like uncontrolled hypertension or diabetes.

Inclusion Criteria

Have a photo identification (ID)

I am able to understand and agree to participate in the study.

Your body mass index (BMI) is between 19 and 24.9.

Exclusion Criteria

Currently enrolled in another research study

You have any health conditions that could make the study more risky for you.

You were born at a place higher than 7,000 feet above sea level.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Hypoxic Exposure

Participants are exposed to a normobaric, low-oxygen environment for five days to monitor physiological and biochemical responses.

5 days

Continuous monitoring

Return to Normoxia

Participants are monitored for physiological and biochemical changes after returning to normal oxygen levels.

2 days

Continuous monitoring

Follow-up

Participants are monitored for safety and effectiveness after the hypoxic exposure period.

1 week

Treatment Details

Interventions

• Inhaled Nitrogen

Trial Overview The study tests the safety of breathing low-oxygen air (inhaled nitrogen) in a controlled environment among healthy volunteers to understand how their bodies respond over time.

Participant Groups

Group I: Inhaled Nitrogen Experimental Treatment 1 Intervention

A humidified mixture of gas will be delivered by mask, nasal cannulae, and small room-sized tent. Inspiratory oxygen fraction (FiO2) will be gradually decreased to 11% over a period or five days to obtain a peripheral capillary O2 saturation (SpO2) between 80%-85% (corresponding to 40-55 mmHg of arterial partial oxygen pressure (PaO2)). Healthy volunteers will be monitored and blood and urine will be obtained at 24h and 48 hours after returning to normoxia.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Karaa, Amel, M.D., Massachusetts General Hospital, Harvard Medical School

Collaborator

Trials

1

Recruited

10+

Fisher, Daniel, R.R.T., Massachusetts General Hospital, Harvard Medical School

Collaborator

Trials

1

Recruited

10+

Jain, Isha, B.A., Massachusetts General Hospital, Harvard Medical School

Collaborator

Trials

1

Recruited

10+

Patel, Sarvagna, B.A., Massachusetts General Hospital, Harvard Medical School

Collaborator

Trials

1

Recruited

10+

Harris, Stuart N., M.D., Massachusetts General Hospital, Harvard Medical School

Collaborator

Trials

1

Recruited

10+

Zapol, Warren M., M.D., Massachusetts General Hospital, Harvard Medical School

Collaborator

Trials

1

Recruited

10+

Mootha, Vamsi, M.D., Massachusetts General Hospital, Harvard Medical School

Collaborator

Trials

1

Recruited

10+

Rezoagli, Emanuele, M.D., Massachusetts General Hospital, Harvard Medical School

Collaborator

Trials

1

Recruited

10+

Ferrari, Michele, M.D., Massachusetts General Hospital, Harvard Medical School

Collaborator

Trials

1

Recruited

10+

Findings from Research

Normobaric hypoxia (NH) can be used as a practical substitute for hypobaric hypoxia (HH) in training and research by adjusting the inspired fraction of oxygen to match the oxygen partial pressure at high altitudes.

However, the physiological responses to NH and HH are not identical, as differences in alveolar gas composition arise due to nitrogen dilution effects, meaning that caution should be taken when interpreting results from NH as directly applicable to HH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Equivalent Air Altitude and the Alveolar Gas Equation. Conkin, J.[2016]

References

1. United States pubmed.ncbi.nlm.nih.gov

Uncontrolled oxygen administration and respiratory failure in acute asthma. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Nasal mucosa inflammation induced by oxygen administration in humans. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

A New Method for Combined Hyperventilation and Hypoxia Training in a Tactical Fighter Simulator. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Carbon dioxide protects simulated driving performance during severe hypoxia. [2023]

5. Brazil pubmed.ncbi.nlm.nih.gov

Systemic effects of nocturnal hypoxemia in patients with chronic obstructive pulmonary disease without obstructive sleep apnea syndrome. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Effect of exposure to 15% oxygen on breathing patterns and oxygen saturation in infants: interventional study. [2019]

7. England pubmed.ncbi.nlm.nih.gov

The physiological effects of hypobaric hypoxia versus normobaric hypoxia: a systematic review of crossover trials. [2020]

8. Netherlands pubmed.ncbi.nlm.nih.gov

The influence of a mouthpiece and noseclip on breathing pattern at rest is reduced at high altitude. [2007]

9. United States pubmed.ncbi.nlm.nih.gov

Equivalent Air Altitude and the Alveolar Gas Equation. [2016]