NCT05612074

Methemoglobin Concentration in High Dose Inhaled Nitric Oxide

Kinetics of Methemoglobin Concentration in Healthy Subjects Exposed to High Dose Inhaled Nitric Oxide

• Status: Active Not Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: Massachusetts General Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 64 Years
• Healthy volunteers: Accepted

Summary

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.

Detailed description

The current proposed physiologic study is a single center, open-label clinical trial in healthy subjects. The primary aim is to describe kinetics of methemoglobin (MetHb) formation and reduction during exposure to high dose inhaled nitric oxide (iNO) at a maximum of 300 parts per million in healthy volunteers. The investigators will also assess the contribution of increased cardiac output in relation to MetHb formation/reduction and of different inspired oxygen concentrations on the production of nitrogen dioxide (NO2). The study protocol consists of breathing iNO at a maximum of 300 parts per million (ppm) and two different FiO2 levels (i.e. 21% and 80%). The combination of iNO and FiO2 levels identifies 2 study cohorts; five different subjects will be enrolled for each cohort. The maximum number of volunteers enrolled in this clinical trial is 10 spontaneously breathing, awake, healthy subjects, divided in two groups (5 volunteers/group, 2 groups). The first 5 subjects will be exposed to iNO in a mixture of gas at 21% of FiO2, the second group of 5 patients will receive iNO a mixture of gas at 80% of FiO2. Each volunteer will be exposed to a maximum of 300 ppm of iNO at 3 times/day for 5 consecutive days. Thus, a maximum of 150 total iNO treatments will be administered (10 enrolled volunteers, 5 days, 3 treatments/day). On the fifth day of the study, the iNO administration will be performed during physical exercise that will increase the respiratory rate of the subject, in order to study the influence of the respiratory rate on the rate of MetHb formation. During each treatment period, a threshold of MetHb = 10% and/or inspiratory NO2 = 5 ppm (as defined by the OSHA, https://www.osha.gov/chemicaldata/21, last accessed on Oct 31, 2022) will be used as stopping criteria for gas inhalation. Also, iNO administration will be stopped at any time, regardless of the MetHb and NO2 levels, at the discretion of the subject.

Conditions

• Healthy Subjects

Interventions

Type	Name	Description
DRUG	Inhaled Nitric Oxide	Inhaled nitric oxide (Medical grade, in NO/N2 tanks) will be delivered in a oxygen-air-nitrogen mixture for 30 minutes three times per day

Timeline

• Start date: 2023-10-16
• Primary completion: 2026-11-01
• Completion: 2027-12-01
• First posted: 2022-11-10
• Last updated: 2025-12-02

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study