Clinical trial NCT05612074: Methemoglobin Concentration in High Dose Inhaled Nitric Oxide
Official title: Kinetics of Methemoglobin Concentration in Healthy Subjects Exposed to High Dose Inhaled Nitric Oxide
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
Conditions: Healthy Subjects
Keywords: nitric oxide
methemoglobin
nitrogen dioxide
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2022-11-10
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Physiologic study in healthy volunteers
Primary purpose: BASIC_SCIENCE

Brief 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.

Eligibility criteria: Inclusion Criteria:

* 18 - 64 years-old volunteers.
* Body Mass Index (BMI) 18 - 30 kg/m2.
* Absence of current systemic and/or respiratory diseases.
* Capacity to consent to the study.

Exclusion Criteria:

* Evidence of any physical, mental, and/or medical conditions that would make the proposed studies relatively more hazardous.
* Systemic and/or respiratory disease with or without any functional limitation.
* Left ventricle ejection fraction \< 30%.
* Baseline MetHb ≥ 3%
* Other conditions of increased risk for MetHb formation: genetic diseases (e.g., glucose-6-phosphate dehydrogenase deficiency, cytochrome b5 reductase deficiency, sickle cell disease), significant anemia or baseline elevation in MetHb.
* History of transient ischemic attack or stroke.
* Active smoking and tobacco chewers. Volunteers may be enrolled if they quit smoking for more than 1 year and less than 10 pack years total.
* Any vaping/e-cigarettes use
* Excess alcohol use: more than ½ L/day of wine consumption or equivalent
* Current use of any recreational drugs (including the use of medical marijuana) or use of recreational drugs over the past year.
* Pregnancy determined by blood pregnancy test detecting presence of human chorionic gonadotropin (hCG).
* Less than six weeks postpartum.
* Any current medication uses except oral contraceptives.
* Lower respiratory infection within the last 30 days.
* Claustrophobia (inability to wear a facemask) or other active psychiatric conditions or unwillingness to cooperate with the investigators and other medical teams.
* Currently enrolled in another research study.
* Facial abnormalities that would preclude proper use of a face mask.

Primary outcomes:
measure: Methemoglobin kinetics
timeFrame: 7 days
Secondary outcomes:
measure: Nitric Oxide Metabolites
timeFrame: 7 days
measure: Nitrogen Dioxide
timeFrame: 5 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Lorenzo Berra, MD
role: PRINCIPAL_INVESTIGATOR
References:
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