Clincosm LogoSign in Get a demo

Methemoglobin Concentration in High Dose Inhaled Nitric Oxide

Sponsor
Massachusetts General Hospital (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05612074
Collaborator
(none)
30
Enrollment
1
Location
1
Arm
35
Anticipated Duration (Months)
0.9
Patients Per Site Per Month

Study Details

Study Description

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 different concentrations 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 while being continuously monitored.

Condition or Disease Intervention/Treatment Phase
  • Drug: Inhaled Nitric Oxide
 Early Phase 1

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) 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 three iNO concentrations (i.e., 200, 250 and 300 parts per million, ppm) and two different FiO2 levels (i.e. 21% and 80%). The combination of iNO concentrations and FiO2 levels identifies 6 study cohorts; five different subjects will be enrolled for each cohort. The maximum number of volunteers enrolled in this clinical trial is 30 spontaneously breathing, awake, healthy subjects, divided in two groups (15 volunteers/group, 2 groups). The first 15 subjects will be exposed to iNO in a mixture of gas at 21% of FiO2, the second group of 15 patients will receive iNO a mixture of gas at 80% of FiO2. The maximum number of enrolled volunteers of 15/group is a product of the number of volunteers exposed to each iNO concentration (5 volunteers/concentration, 3 doses). Each volunteer will be exposed to a single iNO dosage at 3 times/day for 5 consecutive days. Thus, a maximum of 450 total iNO treatments will be administered (30 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
30 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
Physiologic study in healthy volunteersPhysiologic study in healthy volunteers
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
Kinetics of Methemoglobin Concentration in Healthy Subjects Exposed to High Dose Inhaled Nitric Oxide
Anticipated Study Start Date :
Jan 1, 2023
Anticipated Primary Completion Date :
Jun 1, 2025
Anticipated Study Completion Date :
Dec 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Nitric Oxide

High dose inhaled nitric oxide (200, 250 and 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
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
Other Names:
  • Nitric Oxide
  • Gaseous Nitric Oxide

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Methemoglobin kinetics [7 days]

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

    Secondary Outcome Measures

    1. Nitric Oxide Metabolites [7 days]

      Measurement of Nitric Oxide metabolites (urinary and plasma) in subjects exposed to high dose iNO.

    2. Nitrogen Dioxide [5 days]

      Inspiratory NO2 concentrations at different inspiratory concentrations of NO and O2

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 64 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Massachusetts General Hospital Boston Massachusetts United States 02114

    Sponsors and Collaborators

    • Massachusetts General Hospital

    Investigators

    • Principal Investigator: Lorenzo Berra, MD, Massachusetts General Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Lorenzo Berra, MD, Medical Director, Respiratory Care, Massachusetts General Hospital
    ClinicalTrials.gov Identifier:
    NCT05612074
    Other Study ID Numbers:
    • 2022P002884
    First Posted:
    Nov 10, 2022
    Last Update Posted:
    Nov 14, 2022
    Last Verified:
    Nov 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Lorenzo Berra, MD, Medical Director, Respiratory Care, Massachusetts General Hospital
    nitric oxide
    methemoglobin
    nitrogen dioxide
    Additional relevant MeSH terms:
    Nitric Oxide

    Study Results

    No Results Posted as of Nov 14, 2022