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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and bodily response when healthy individuals breathe air with reduced oxygen levels using inhaled nitrogen. It seeks to understand the body's reactions when oxygen levels drop, mimicking high-altitude conditions. Suitable participants should be healthy, free of asthma, and reside in lower-altitude areas. As an unphased study, this trial provides a unique opportunity to contribute to scientific knowledge of how the body adapts to low-oxygen environments.

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.

What prior data suggests that this hypoxic breathing protocol is safe for healthy volunteers?

Research shows that inhaling nitrogen is generally safe when mixed with sufficient oxygen. Excessive nitrogen reduces oxygen levels, which can be dangerous. For instance, breathing air with insufficient oxygen can cause rapid fainting.

In everyday environments, nitrogen constitutes a large part of the air and poses no harm. However, low oxygen levels can be risky. Studies have found that health problems can occur if nitrogen exceeds 80% of the air.

While nitrogen itself isn't harmful, maintaining adequate oxygen levels is crucial for safe breathing. The study carefully monitors this balance to ensure safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the inhaled nitrogen protocol because it explores how safely reducing oxygen levels can be managed in healthy individuals. Unlike typical treatments that directly address oxygen deprivation, this method gradually lowers oxygen intake using a humidified nitrogen gas mixture. The unique delivery method—via a mask, nasal cannulae, and even a small tent—allows precise control over oxygen levels, aiming to understand the body's response to hypoxia. This innovative approach could pave the way for new insights into managing conditions related to oxygen deficiency.

What evidence suggests that inhaled nitrogen is effective for hypoxic breathing safety?

Research has shown that inhaled nitric oxide can safely and effectively assist people with breathing problems, such as those caused by COVID-19 pneumonia, by improving blood oxygen levels. However, participants in this trial will inhale nitrogen to create a low-oxygen environment. The main goal is to determine the safety of breathing reduced oxygen levels for several days. While nitrogen can be safe when properly mixed with oxygen, careful management is essential. This study will assess the body's reaction to reduced oxygen levels. ^{1 6 7 8 9}

Who Is on the Research Team?

Lorenzo Berra, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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

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.

Currently enrolled in another research study

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8361002/

Inhaled high dose nitric oxide is a safe and effective ... Inhaled high dose nitric oxide is a safe and effective respiratory treatment in spontaneous breathing hospitalized patients with COVID-19 pneumonia.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02860975

Prolonged Hypoxic Breathing in Healthy Volunteers: a ... The primary endpoint of this research study is to prove safety in healthy subjects breathing humidified hypoxic inspiratory gas mixture for 5 days.

3. csb.gov csb.gov/hazards-of-nitrogen-asphyxiation/

Hazards of Nitrogen Asphyxiation | CSB Nitrogen is safe to breathe only when mixed with the appropriate amount of oxygen. These two gases cannot be detected by the sense of smell.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6295404/

Inhaled nitric oxide - PMC Treatment with inhaled 80 p.p.m. NO during (via oxygenator) and for 24 h after the operation was safe, with blood methaemoglobin levels remaining below 10%.

5. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf20/P200044B.pdf

SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) The NO generated by the LungFit® PH System is indicated to improve oxygenation and reduce the need for extracorporeal membrane oxygenation in term and near-term ...

6. csb.gov csb.gov/assets/1/20/nitrogen_asphyxiation_bulletin_training_presentation.pdf?15062

The Hazards of Nitrogen Asphyxiation However, nitrogen is safe to breath only if it is mixed with an appropriate amount of oxygen. Additional nitrogen (lower oxygen) cannot be detected by the ...

7. nj.gov nj.gov/health/eoh/rtkweb/documents/fs/1375.pdf

workplace exposure limits HAZARD SUMMARY. * Nitrogen is present in the air we breathe. The health effects described in this Fact Sheet may occur at concentrations greater than 80%.

8. dpic-cdn.org dpic-cdn.org/production/legacy/Copeland%20Report_Nitrogen-Hypoxia.pdf

Nitrogen Induced Hypoxia as a Form of Capital Punishment When combined with the normal 20.95% oxygen found in the atmosphere, nitrogen is completely safe for humans to inhale. However, an environment overly enriched ...

9. airproducts.com airproducts.com/-/media/files/en/312/312-12-023-us-use-nitrogen-safely.pdf

Use Nitrogen Safely At extremely low oxygen concentrations, unconsciousness and death may occur in seconds and without warning. The U.S. Occupational Safety and Health Administra-.