Inhaled Nitric Oxide for Healthy Subjects

Overseen By Lorenzo Berra, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Massachusetts General Hospital

Must not be taking: Recreational drugs

Disqualifiers: Respiratory disease, Anemia, Smoking, Pregnancy, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

Duration: 5 days

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The goal of this clinical trial is to learn about the kinetic of methemoglobin in healthy subjects breathing high dose inhaled nitric oxide. The main questions it aims to answer are: * What are the kinetics of methemoglobin formation at a maximum of 300 parts per million of nitric oxide and oxygen * What are the kinetics of methemoglobin reduction after nitric oxide discontinuation Participants will be exposed to intermittent high dose inhaled nitric oxide at a maximum of 300 parts per million while being continuously monitored.

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 trial.

Is inhaled nitric oxide generally safe for humans?

Inhaled nitric oxide (iNO) has been used safely in various medical settings, including critical care transport and treatment of premature infants. Some studies have noted potential risks, such as low blood pressure and kidney issues, but these are often manageable with proper medical supervision. ^{1 2 3 4 5}

How is the drug inhaled nitric oxide unique compared to other treatments?

Inhaled nitric oxide is unique because it is administered directly into the lungs as a gas, which allows it to act quickly and directly on the airways. This is different from many other treatments that are taken orally or injected, and it is particularly useful for rapidly assessing and managing airway inflammation. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment Inhaled Nitric Oxide?

Inhaled nitric oxide is used as a rescue treatment to improve oxygen levels in patients with severe breathing difficulties, such as those with severe hypoxemia (low blood oxygen levels) or severe COVID-19 pneumonia. ^{11 12 13 14 15}

Who Is on the Research Team?

Lorenzo Berra, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for healthy volunteers aged 18-64 with a BMI of 18-30 kg/m^2, no respiratory diseases, and not currently on medication (except oral contraceptives). Smokers or those who use recreational drugs including marijuana are excluded. Pregnant women and individuals with certain genetic diseases or recent infections are also ineligible.

Inclusion Criteria

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

Body Mass Index (BMI) 18 - 30 kg/m2

I do not have any ongoing illnesses affecting my body or lungs.

Exclusion Criteria

Less than six weeks postpartum

Current use of any recreational drugs (including the use of medical marijuana) or use of recreational drugs over the past year

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

Treatment

Participants receive high dose inhaled nitric oxide at a maximum of 300 ppm, three times per day for 5 consecutive days

5 days

15 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including methemoglobin reduction kinetics

2 days

What Are the Treatments Tested in This Trial?

Interventions

• Inhaled Nitric Oxide

Trial Overview The study tests how the body processes methemoglobin when breathing high doses of inhaled nitric oxide up to 300 parts per million. It looks at how quickly methemoglobin forms and reduces after stopping nitric oxide, monitoring participants continuously during exposure.

How Is the Trial Designed?

Group I: Nitric Oxide Experimental Treatment 1 Intervention

High dose inhaled nitric oxide (targeting 250 ppm and not exceeding 300 ppm) in a nitrogen-oxygen-air mixture, at two different FiO2 levels (0.21 and 0.8) will be delivered intermittently with a dedicated system and a snug-fitting facemask to healthy volunteers three times per day for 5 days. The subjects will be monitored before, during and after the administration

Inhaled Nitric Oxide is already approved in United States, European Union for the following indications:

Approved in United States as INOmax for:

• Hypoxic respiratory failure
• Pulmonary hypertension

Approved in United States as Genosyl for:

• Hypoxic respiratory failure
• Pulmonary hypertension

Approved in European Union as INOmax for:

• Persistent pulmonary hypertension of the newborn
• Acute hypoxic respiratory failure

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

Inhaled nitric oxide (iNO) significantly improved oxygen levels in patients with severe hypoxemia, with arterial oxygen partial pressure (PaO2) increasing from 60.7 to 72.3 mm Hg after treatment (P=.008).

The use of iNO allowed for safe transport of patients to a tertiary care center, with 60.2% of those treated surviving to discharge, compared to a 50% survival rate in patients transported without iNO.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled nitric oxide to improve oxygenation for safe critical care transport of adults with severe hypoxemia. Teman, NR., Thomas, J., Bryner, BS., et al.[2020]

The implementation of clinical guidelines for inhaled nitric oxide (iNO) therapy in a pediatric intensive care unit led to a significant reduction in the duration of iNO treatment, from a median of 162 hours to 76 hours, without compromising patient care.

Following the guidelines, there was a notable cost savings of $4,600 per patient, demonstrating that standardized protocols can enhance efficiency and reduce unnecessary expenses in iNO therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Quality Improvement Initiative to Standardize Use of Inhaled Nitric Oxide in the PICU. Karsies, TJ., Evans, L., Frost, R., et al.[2022]

Inhaled nitric oxide (iNO) can be safely managed by trained nurses during the transport of critically ill patients, as demonstrated by a study involving patients transported from March 2020 to August 2022.

Out of the patients studied, only 16.7% experienced hypotension, which was manageable and resolved with medication adjustments, while no serious adverse events like worsening hypoxemia or cardiac arrest were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Nurse-Managed Inhaled Nitric Oxide During Critical Care Interfacility Transport. Troncoso, R., Garfinkel, EM., Kaul, K., et al.[2023]

Inhaled nitric oxide (iNO) therapy significantly increases the risk of renal dysfunction in patients with acute respiratory distress syndrome (ARDS), with an adjusted hazard ratio of 1.59 after accounting for confounding factors.

Older patients (aged 65 and above) are particularly vulnerable to kidney injury associated with iNO therapy, highlighting the need for careful monitoring in this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled nitric oxide and the risk of renal dysfunction in patients with acute respiratory distress syndrome: a propensity-matched cohort study. Ruan, SY., Wu, HY., Lin, HH., et al.[2022]

In a study of 860 premature infants under 32 weeks, low-dose inhaled nitric oxide (iNO) did not significantly improve intact survival at 28 days compared to placebo, with survival rates of 61.4% for iNO and 61.1% for controls.

The use of iNO was found to be safe, showing no significant differences in major complications like intraventricular hemorrhage, necrotizing enterocolitis, or patent ductus arteriosus compared to controls, suggesting it does not increase the risk of these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of nitric oxide therapy in premature infants. Hascoet, JM., Fresson, J., Claris, O., et al.[2016]

Citations

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

Inhaled nitric oxide to improve oxygenation for safe critical care transport of adults with severe hypoxemia. [2020]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical indication for use and outcomes after inhaled nitric oxide therapy. [2022]

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

High-Dose Inhaled Nitric Oxide for the Treatment of Spontaneously Breathing Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19) Pneumonia. [2023]

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

Off-label use of inhaled nitric oxide after release of NIH consensus statement. [2015]

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

A Quality Improvement Initiative to Standardize Use of Inhaled Nitric Oxide in the PICU. [2022]

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

Safety of Nurse-Managed Inhaled Nitric Oxide During Critical Care Interfacility Transport. [2023]

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

Inhaled nitric oxide and the risk of renal dysfunction in patients with acute respiratory distress syndrome: a propensity-matched cohort study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Inhaled nitric oxide and acute kidney injury risk: a meta-analysis of randomized controlled trials. [2021]

9. Norway pubmed.ncbi.nlm.nih.gov

Use of inhaled nitric oxide in the new born period: results from the European Inhaled Nitric Oxide Registry. [2013]

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

The safety and efficacy of nitric oxide therapy in premature infants. [2016]

11. Spain pubmed.ncbi.nlm.nih.gov

A snapshot of exhaled nitric oxide and asthma characteristics: experience from high to low income countries. [2022]

12. Australia pubmed.ncbi.nlm.nih.gov

Comparison of two exhaled nitric oxide analyzers: the NIOX MINO hand-held electrochemical analyzer and the NOA280i stationary chemiluminescence analyzer. [2013]

13. England pubmed.ncbi.nlm.nih.gov

Exhaled nitric oxide in pediatric patients with respiratory disease. [2020]

14. England pubmed.ncbi.nlm.nih.gov

Exhaled nitric oxide and inducible nitric oxide synthase gene polymorphism in Japanese asthmatics. [2017]

15. England pubmed.ncbi.nlm.nih.gov

High fractional concentration of nitric oxide in exhaled air despite steroid treatment in asthmatic children. [2013]