Methemoglobin Concentration in High Dose Inhaled Nitric Oxide

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.

Timeline

Start

2023-10-16

Primary completion

2026-11

Completion

2027-12

Publications

• Background 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Dong R, Wanderley HV, Mereto E, Safaee Fakhr B, Nardini R, Yu B, Berra L. Breath-by-breath quantification of inhaled nitric oxide absorption and modeling of methemoglobin kinetics. Redox Biol. 2026 May;92:104125. doi: 10.1016/j.redox.2026.104125. Epub 2026 Mar 12.

Drugs

Indications

No indication recorded.