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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how the body processes methemoglobin (a type of hemoglobin that can affect oxygen delivery) when healthy individuals inhale high doses of nitric oxide, a gas used in medical treatments. Researchers aim to understand how quickly methemoglobin forms and returns to normal after stopping the nitric oxide. Participants will inhale this gas mixture three times a day for five days while under close monitoring. The trial seeks healthy volunteers without major health issues who are comfortable wearing a face mask. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to contribute to groundbreaking medical knowledge.

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 there any evidence suggesting that inhaled nitric oxide is likely to be safe for humans?

Research has shown that inhaled nitric oxide is generally safe when used carefully. The FDA has approved it for treating certain lung issues in newborns, indicating it has been studied and found safe for that purpose. Some studies indicate that common side effects include low blood pressure, occurring in about 14% of cases where nitric oxide was used, compared to 11% with a placebo.

Stopping high doses suddenly can cause problems, such as worsening lung function or increased blood pressure in the lungs, emphasizing the need for careful monitoring during use. Nitric oxide can also affect DNA, but this concern arises mainly at very high doses or with long-term exposure.

Overall, while inhaled nitric oxide is generally well-tolerated, monitoring during use is crucial to manage side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Inhaled nitric oxide is unique because it delivers a high dose of nitric oxide directly to the lungs using a specialized system and snug-fitting facemask. This method allows for targeted treatment, potentially offering more immediate and controlled effects compared to systemic therapies. Researchers are excited about this approach because it could provide a novel way to manage conditions quickly, with adjustments possible based on the oxygen levels in the mixture, offering a tailored treatment experience.

What evidence suggests that inhaled nitric oxide is effective for studying methemoglobin kinetics?

Research has shown that inhaled nitric oxide (INO) is generally safe and well-tolerated in healthy individuals. One study found that inhaling 160 parts per million (ppm) of nitric oxide for 30 minutes, five times a day, over five days was safe. This study involved healthy individuals, similar to those in this trial. In this trial, participants will receive high-dose inhaled nitric oxide, targeting 250 ppm and not exceeding 300 ppm, delivered intermittently. INO relaxes and widens blood vessels, improving blood flow and oxygen delivery. The treatment has been effective in managing certain breathing problems, such as low oxygen levels in the blood, in other studies. While most data focuses on specific conditions, the safety results in healthy individuals encourage further research. ^{6 7 8 9 10}

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) 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]

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]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT00922532

Inhaled Nitric Oxide (INO) In Hypoxic Respiratory Failure This Phase 3, Double-blind, Randomized, Placebo controlled, multicenter study is to confirm the efficacy of inhaled nitric oxide for the management of hypoxic ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1569199312000057

A phase I clinical study of inhaled nitric oxide in healthy ... These data suggest that inhalation of 160 ppm NO for 30 min, 5 times daily, for 5 consecutive days, is safe and well tolerated in healthy individuals. Previous ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10913844/

A Comprehensive Review of Inhaled Nitric Oxide Therapy This comprehensive review explores the multifaceted landscape of inhaled nitric oxide (iNO) therapy, tracing its historical evolution, mechanisms of action, ...

4. sph.uth.edu sph.uth.edu/news/story/uthealth-houston-to-lead-data-coordinating-center-on-114m-multi-site-clinical-trial

UTHealth Houston to Lead Data Coordinating Center on ... Previous observational evidence suggests a lack of effectiveness and potential harm from iNO among neonates with CDH, yet it is still widely ...

5. withpower.com withpower.com/trial/early-phase-1-healthy-subjects-hs-2023-7279b

Inhaled Nitric Oxide for Healthy Subjects · Info for Participants 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) ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2010/020845s011lbl.pdf

INOmax (nitric oxide) for inhalation - accessdata.fda.gov Worsening oxygenation and increasing pulmonary artery pressure occur if INOmax is discontinued abruptly. Other adverse reactions that occurred in more than 5% ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/nitric-oxide-inhalation-route/description/drg-20060881

Nitric oxide (inhalation route) - Side effects & uses Nitric oxide is a gas that is inhaled through the nose or mouth. It works by relaxing the smooth muscles to widen the blood vessels in the lungs.

8. inomax.com inomax.com/efficacy-and-safety

Efficacy & Safety | INOmax® (nitric oxide) gas, for inhalation The most common adverse reaction was hypotension (14% vs 11%; >2% higher incidence on INOmax than on placebo) · 2/97 patients (2%) were withdrawn from study drug ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/11134540/

The toxicology of inhaled nitric oxide - PubMed - NIH Nitric oxide has also been shown to cause DNA strand breaks and/or base alterations that are potentially mutagenic. Inhaled nitric oxide can rapidly react with ...

10. reference.medscape.com reference.medscape.com/drug/inomax-genosyl-nitric-oxide-gas-343457

INOmax, Genosyl - nitric oxide gas - Medscape Reference nitric oxide gas (Rx) ; Adverse Effects. >10% ; Warnings. Contraindications ; Pregnancy & Lactation. Pregnancy ; Pharmacology. Mechanism of Action ; Administration ...