Methemoglobin Concentration in High Dose Inhaled Nitric Oxide

NCT05612074 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 2022P002884
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Subjects

Keywords

nitric oxide; methemoglobin; nitrogen dioxide

Outcome Measures

Primary Outcomes (1)

• Methemoglobin kinetics

  Levels of methemoglobin formation and reduction during and after exposure to high dose inhaled nitric oxide

  7 days

Secondary Outcomes (2)

• Nitric Oxide Metabolites

  7 days

• Nitrogen Dioxide

  5 days

Study Arms (1)

Nitric Oxide

EXPERIMENTAL

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

Drug: Inhaled Nitric Oxide

Interventions

Inhaled Nitric Oxide DRUG

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

Also known as: Nitric Oxide, Gaseous Nitric Oxide

Nitric Oxide

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (10)

• Wiegand SB, Traeger L, Nguyen HK, Rouillard KR, Fischbach A, Zadek F, Ichinose F, Schoenfisch MH, Carroll RW, Bloch DB, Zapol WM. Antimicrobial effects of nitric oxide in murine models of Klebsiella pneumonia. Redox Biol. 2021 Feb;39:101826. doi: 10.1016/j.redox.2020.101826. Epub 2020 Dec 11.

  PMID: 33352464 BACKGROUND

• Di Fenza R, Yu B, Carroll RW, Berra L. Chemiluminescence-based Assays for Detection of Nitric Oxide and its Derivatives from Autoxidation and Nitrosated Compounds. J Vis Exp. 2022 Feb 16;(180). doi: 10.3791/63107.

  PMID: 35253799 BACKGROUND

• Valsecchi C, Winterton D, Safaee Fakhr B, Collier AY, Nozari A, Ortoleva J, Mukerji S, Gibson LE, Carroll RW, Shaefi S, Pinciroli R, La Vita C, Ackman JB, Hohmann E, Arora P, Barth WH Jr, Kaimal A, Ichinose F, Berra L; DELiverly oF iNO (DELFiNO) Network Collaborators. High-Dose Inhaled Nitric Oxide for the Treatment of Spontaneously Breathing Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19) Pneumonia. Obstet Gynecol. 2022 Aug 1;140(2):195-203. doi: 10.1097/AOG.0000000000004847. Epub 2022 Jul 6.

  PMID: 35852269 BACKGROUND

• Safaee Fakhr B, Di Fenza R, Gianni S, Wiegand SB, Miyazaki Y, Araujo Morais CC, Gibson LE, Chang MG, Mueller AL, Rodriguez-Lopez JM, Ackman JB, Arora P, Scott LK, Bloch DB, Zapol WM, Carroll RW, Ichinose F, Berra L; Nitric Oxide Study Investigators. Inhaled high dose nitric oxide is a safe and effective respiratory treatment in spontaneous breathing hospitalized patients with COVID-19 pneumonia. Nitric Oxide. 2021 Nov 1;116:7-13. doi: 10.1016/j.niox.2021.08.003. Epub 2021 Aug 13.

  PMID: 34400339 BACKGROUND

• Bartley BL, Gardner KJ, Spina S, Hurley BP, Campeau D, Berra L, Yonker LM, Carroll RW. High-Dose Inhaled Nitric Oxide as Adjunct Therapy in Cystic Fibrosis Targeting Burkholderia multivorans. Case Rep Pediatr. 2020 Jun 24;2020:1536714. doi: 10.1155/2020/1536714. eCollection 2020.

  PMID: 32685229 BACKGROUND

• Miller C, Miller M, McMullin B, Regev G, Serghides L, Kain K, Road J, Av-Gay Y. A phase I clinical study of inhaled nitric oxide in healthy adults. J Cyst Fibros. 2012 Jul;11(4):324-31. doi: 10.1016/j.jcf.2012.01.003. Epub 2012 Apr 18.

  PMID: 22520076 BACKGROUND

• Wiegand SB, Safaee Fakhr B, Carroll RW, Zapol WM, Kacmarek RM, Berra L. Rescue Treatment With High-Dose Gaseous Nitric Oxide in Spontaneously Breathing Patients With Severe Coronavirus Disease 2019. Crit Care Explor. 2020 Nov 16;2(11):e0277. doi: 10.1097/CCE.0000000000000277. eCollection 2020 Nov.

  PMID: 33225304 BACKGROUND

• Safaee Fakhr B, Wiegand SB, Pinciroli R, Gianni S, Morais CCA, Ikeda T, Miyazaki Y, Marutani E, Di Fenza R, Larson GM, Parcha V, Gibson LE, Chang MG, Arora P, Carroll RW, Kacmarek RM, Ichinose F, Barth WH Jr, Kaimal A, Hohmann EL, Zapol WM, Berra L. High Concentrations of Nitric Oxide Inhalation Therapy in Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19). Obstet Gynecol. 2020 Dec;136(6):1109-1113. doi: 10.1097/AOG.0000000000004128.

  PMID: 32852324 BACKGROUND

• Pinciroli R, Traeger L, Fischbach A, Gianni S, Morais CCA, Fakhr BS, Di Fenza R, Robinson D, Carroll R, Zapol WM, Berra L. A Novel Inhalation Mask System to Deliver High Concentrations of Nitric Oxide Gas in Spontaneously Breathing Subjects. J Vis Exp. 2021 May 4;(171). doi: 10.3791/61769.

  PMID: 34028428 BACKGROUND

• Gianni S, Fenza RD, Morais CCA, Fakhr BS, Mueller AL, Yu B, Carroll RW, Ichinose F, Zapol WM, Berra L. High-Dose Nitric Oxide From Pressurized Cylinders and Nitric Oxide Produced by an Electric Generator From Air. Respir Care. 2022 Feb;67(2):201-208. doi: 10.4187/respcare.09308. Epub 2021 Aug 19.

  PMID: 34413210 BACKGROUND

MeSH Terms

Interventions

Nitric Oxide

Intervention Hierarchy (Ancestors)

Reactive Nitrogen Species; Free Radicals; Inorganic Chemicals; Nitrogen Oxides; Nitrogen Compounds; Oxides; Oxygen Compounds; Organic Chemicals

Study Officials

• Lorenzo Berra, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director, Respiratory Care

Model Details: Physiologic study in healthy volunteers

Study Record Dates

• First Submitted: October 31, 2022
• First Posted: November 10, 2022
• Study Start: October 16, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 2, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)