Inhaled Nitric Oxide in Severe Obesity

NCT ID: NCT06675435

Last Updated: 2025-02-04

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-31
• Study Completion Date: 2027-12-31

Brief Summary

The goal of this clinical trial is to learn about the effects of inhaled nitric oxide on oxygenation and lung perfusion in participants with severe obesity who have acute hypoxemic respiratory failure and are on mechanical ventilation

The main questions it aims to answer are:

1. In acute hypoxemic respiratory failure, what are the effects of inhaled nitric oxide on oxygenation in participants with severe obesity compared to participants with normal body weight.

2. In acute hypoxemic respiratory failure, what are the effects of inhaled nitric oxide on lung perfusion and heart function in participants with severe obesity compared to participants with normal body weight.

3. In acute hypoxemic respiratory failure, does severe obesity impact nitric oxide signaling pathways?

Participants with acute hypoxemic respiratory failure will be exposed to inhaled nitric oxide (20 ppm) while being clinically monitored.

Detailed Description

The study is a single-center, open-label clinical trial in mechanically ventilated participants with acute hypoxemic respiratory failure. The primary aim is to assess changes in intrapulmonary shunt (primary study outcome) to inhaled nitric oxide in participants with severe obesity and those with normal body weight. The secondary aims are to determine differences in regional lung perfusion (measured by electrical impedance tomography), right ventricular pressure (measured by transthoracic echocardiography), and biomarkers of nitric oxide signaling dysfunction (nitric oxide activity, pro-inflammatory cytokines, endothelial glycocalyx fragments)

The primary study intervention involves inhaled nitric oxide at 20 ppm for 15 minutes. The investigators will compare inhaled nitric oxide response in participants with severe obesity (defined by body mass index greater than or equal to 40) to participants with normal body weight (defined by body mass index 18.5-24.9). 40 participants with acute hypoxemic respiratory failure will be enrolled (20 with severe obesity and 20 with normal body weight). The investigators will enroll a separate cohort of mechanically ventilated participants who do not have acute hypoxemic respiratory failure (10 with severe obesity and 10 with normal body weight). In this cohort, investigators will collect additional blood at a single time point to compare levels of nitric oxide signaling pathways between patients with and without acute hypoxemia across body weight.

Conditions

Obesity; Respiratory Insufficiency; Hypoxemic Respiratory Failure; Nitric Oxide

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Acute hypoxemic respiratory failure

Participants (n = 40) with acute hypoxemic respiratory failure will receive inhaled nitric oxide (20 ppm) for 15 min.

Group Type: EXPERIMENTAL

Nitric oxide

Intervention Type: DEVICE

20ppm for 15 minutes delivered by INO max(Nitric Oxide) Company : INO therapeutics, Inc.

Participants without acute hypoxemic respiratory failure

Participants (n = 20) without acute hypoxemic respiratory failure will not receive inhaled nitric oxide

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Nitric oxide

20ppm for 15 minutes delivered by INO max(Nitric Oxide) Company : INO therapeutics, Inc.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Acute hypoxemic respiratory failure, defined as persistent hypoxemia (PaO2/FiO2 ≤ 300 mmHg or SpO2/FiO2 ≤ 315) and on invasive mechanical ventilation for < 72 hours
• Presence of an arterial and central venous catheter (for blood gas measurement)
• Admitted to a participating MGH ICU

• Receiving invasive mechanical ventilation and do not have a diagnosis of acute hypoxemic respiratory failure (PaO2/FiO2 > 300 mmHg or SpO2/FiO2> 315)
• Presence of an arterial catheter
• Admitted to a participating MGH ICU

Exclusion Criteria

• Age < 18 years
• Pregnancy or known active breastfeeding
• Prisoner or Incarceration
• Inability or unwillingness of subject or legal surrogate/representative to give written informed consent
• Use of inhaled or oral pulmonary vasodilatory therapy within the 24 hours preceding study enrollment
• Contraindication to inhaled NO

• Baseline Methemoglobin ≥ 3%
• Known left ventricle ejection fraction < 20%
• Known history of G6PD deficiency or cytochrome issues
• Prior adverse reaction to inhaled nitric oxide
• Presence of pneumothorax or acute pulmonary embolism
• Chronic hypoxemia requiring home supplemental non-invasive oxygen (nasal cannula or positive pressure ventilation) or home mechanical ventilation
• Chronic pulmonary vascular disease on home chemical vasodilator support (e.g., sildenafil)
• History of lung resection or transplant
• Hemodynamic instability at the time of potential study enrollment defined as:

• Persistent systolic blood pressure < 90 mmHg or >180 mmHg despite the use of vasopressor or vasodilators or
• Requiring an increment in inotropic-vasopressors over the past two hours just before enrollment: more than 15 mcg/min for norepinephrine and dopamine, more than 10 mcg/min in epinephrine; and more than 50 mcg/ min for phenylephrine.

EIT assessments of lung perfusion will only be performed in participants who are already receiving neuromuscular blocking agents (e.g., cisatracurium) at the time of study enrollment. EIT assessments of lung perfusion will not be performed in participants who have the following contraindications to EIT perfusion monitoring:

• Hypernatremia (serum sodium > 150 mEq/L)
• Usage of any devices with electric current generation such as pacemaker or internal cardiac defibrillator

For controls without acute hypoxemic respiratory failure

• Age < 18 years
• Pregnancy or known active breastfeeding
• Prisoner or Incarceration
• Inability or unwillingness of subject or legal surrogate/representative to give written informed consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Timothy G. Gaulton, MD

Assistant Professor of Anaesthesia

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

Central Contacts

Timothy Gaulton, MD, MSc

Role: CONTACT

tgaulton@mgh.harvard.edu

6177263030

Maurizio Cereda, MD

Role: CONTACT

mcereda@mgh.harvard.edu

6177263030

Facility Contacts

Timothy Gaulton, MD, Msc

Role: primary

tgaulton@mgh.harvard.edu

617-726-3030

References

Spina S, Marrazzo F, Morais CCA, Victor M, Forlini C, Guarnieri M, Bastia L, Giudici R, Bassi G, Xin Y, Cereda M, Amato M, Langer T, Berra L, Fumagalli R. Modulation of pulmonary blood flow in patients with acute respiratory failure. Nitric Oxide. 2023 Jul 1;136-137:1-7. doi: 10.1016/j.niox.2023.05.001. Epub 2023 May 10.

Reference Type: BACKGROUND

PMID: 37172929 (View on PubMed)

Borges JB, Suarez-Sipmann F, Bohm SH, Tusman G, Melo A, Maripuu E, Sandstrom M, Park M, Costa EL, Hedenstierna G, Amato M. Regional lung perfusion estimated by electrical impedance tomography in a piglet model of lung collapse. J Appl Physiol (1985). 2012 Jan;112(1):225-36. doi: 10.1152/japplphysiol.01090.2010. Epub 2011 Sep 29.

Reference Type: BACKGROUND

PMID: 21960654 (View on PubMed)

Other Identifiers

2024p003089

Identifier Type: -

Identifier Source: org_study_id