A Mechanistic Study of Inhaled Nitric Oxide in COPD

Study on the Mechanism of Inhaled Nitric Oxide in the Treatment of Patients With Chronic Obstructive Pulmonary Disease (COPD) Complicated With Pulmonary Hypertension

There is a lack of effective treatments for chronic obstructive pulmonary disease (COPD) complicated with pulmonary hypertension. Previous studies have found that inhaled nitric oxide (iNO) can reduce pulmonary artery pressure and improve exercise capacity in COPD with pulmonary hypertension patients. However, the specific mechanism is unclear. The study aims to evaluate pulmonary ventilation/perfusion, pulmonary artery pressure, oxygenation, symptoms and quality of life in COPD with pulmonary hypertension patients after short-term treatment with iNO. Observing a series of pathophysiological changes caused by the treatment of pulmonary hypertension with iNO in COPD, the investigators hope to provide new theoretical basis and research ideas.

Study Overview

• Status: Recruiting
• Conditions: Chronic Obstructive Pulmonary Disease; Pulmonary Hypertension
• Intervention / Treatment: Device: Nitric Oxide Generation and Delivery System

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zhou Fang; Phone Number: +8615655595707; Email: zhou.fang@novlead.com
• Study Contact Backup: Name: Ruoxi He; Phone Number: +8618874167666; Email: heruoxi1985@yeah.net

Study Locations

• China
  • Beijing, China
    • Recruiting
    • China-Japan Friendship Hospital
    • Contact: Ke HUANG, M.D.; Phone Number: 010-84206408

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 40 years, ≤ 75 years
2. Currently smoking or former smokers with at least 10 pack-years of tobacco cigarette smoking history
3. Diagnosis of moderate and severe COPD by the Global initiative for chronic Obstructive Lung Disease (GOLD) 2022 criteria: A post-bronchodilatory forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) < 0.7, and 30%< FEV1 < 80% predicted
4. Echocardiogram with technical adequacy demonstrating with Pulmonary Hypertension: Tricuspid regurgitation velocity (TRV) > 2.8 m/s or pulmonary arterial systolic pressure (sPAP) ≥38mmHg
5. Signed informed consent prior to the initiation of any study mandated procedures or assessments

Exclusion Criteria:

1. Experienced an exacerbation requiring start of or increase in systemic oral corticosteroid therapy during the last month
2. Treatment with antibiotics
3. Respiratory failure requiring supplemental oxygen therapy
4. A diagnosis of Interstitial lung disease, asthma, tuberculosis, bronchiectasis, pneumonia, lung cancer, pulmonary embolism, or other non-COPD respiratory disease
5. Any history of lung resection
6. Left ventricular dysfunction: left ventricular ejection fraction (LVEF) < 40%
7. Clinically significant valvular heart disease, including aortic valvular disease (moderate or greater aortic stenosis or regurgitation) and/or mitral valve disease (moderate or greater mitral stenosis or regurgitation), or status post mitral valve replacement
8. Use within 30 days of screening or current use of approved PH medications such as sildenafil, bosentan or prostacyclines
9. Neuromuscular disease or musculoskeletal injuries that unable to complete exercise trials
10. Use of investigational drugs or devices within 30 days prior to enrollment into the study
11. Any underlying medical or psychiatric condition that, in the opinion of the Investigator, makes the subject an unsuitable candidate for the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inhaled Nitric Oxide (iNO); iNO 20ppm，≥8 hours/day for 3 days	Device: Nitric Oxide Generation and Delivery System; The Nitric Oxide Generation and Delivery System is used to deliver nitric oxide for inhalation therapy into the inspiratory limb of the patient breathing circuit in a way that provides a constant concentration of nitric oxide (NO), as set by the user, to the patient throughout the inspired breath.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilation-perfusion ratio	Change in ventilation-perfusion ratio (V/Q) from Baseline after treatment with iNO, measured by pulmonary ventilation/perfusion imaging	Baseline, Minutes 30
Tricuspid regurgitation velocity (TRV)	Change in TRV from Baseline after treatment with iNO, measured by echocardiogram	Baseline, Day 3
Pulmonary arterial systolic pressure (sPAP)	Change in sPAP from Baseline after treatment with iNO, measured by echocardiogram	Baseline, Day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary function:Forced expiratory volume in 1 second（FEV1）	Change in FEV1 from Baseline after treatment with iNO	Baseline, Day 3
Pulmonary function: Forced vital capacity （FVC）	Change in FVC from Baseline after treatment with iNO	Baseline, Day 3
Pulmonary function: FEV1/FVC	Change in ratio of FEV1 and FVC (FEV1/FVC) from Baseline after treatment with iNO	Baseline, Day 3
Pulmonary function: Diffusion lung capacity for carbon monoxide（DLCO)	Change in DLCO from Baseline after treatment with iNO	Baseline, Day 3
Cardiopulmonary Exercise Test: Maximal oxygen uptake（VO2max）	Change in VO2max from Baseline after treatment with iNO	Baseline, Day 3
Cardiopulmonary Exercise Test: Anaerobic threshold（AT）	Change in AT from Baseline after treatment with iNO	Baseline, Day 3
Cardiopulmonary Exercise Test: Minute ventilation-to-carbon dioxide output（VE/VCO2）	Change in VE/VCO2 from Baseline after treatment with iNO	Baseline, Day 3
Cardiopulmonary Exercise Test: Physiological dead space ventilation (physiological deadspace volume/tidal volume, Vd/Vt)	Change in Vd/Vt from Baseline after treatment with iNO	Baseline, Day 3
Six-minute walk distance (6MWD)	Change in 6MWD from Baseline after treatment with iNO	Baseline, Day 3
Arterial blood gas: Arterial partial pressure of oxygen (PaO2)	Change in PaO2 from Baseline after treatment with iNO	Baseline, Day 3
Arterial blood gas: Arterial partial pressure of carbon dioxide (PaCO2)	Change in PaCO2 from Baseline after treatment with iNO	Baseline, Day 3
Arterial blood gas: Alveolar-arterial oxygen partial pressure difference (A-aDO2)	Change in A-aDO2 from Baseline after treatment with iNO	Baseline, Day 3
Life quality and symtom severity questionnaires: COPD assessment test (CAT)	Change in CAT scores (0-40 scores, higher scores mean a worse outcome) from Baseline after treatment with iNO	Baseline, Day 3
Life quality and symtom severity questionnaires: Modified Medical Research Council (mMRC) Dyspnea Scale	Change in (mMRC) Dyspnea Scale scores (0-4 scores, higher scores mean a worse outcome) from Baseline after treatment with iNO	Baseline, Day 3
Life quality and symtom severity questionnaires: Saint George Respiratory Questionnaire (SGRQ)	Change in SGRQ scores (0-100 scores, higher scores mean a worse outcome) from Baseline after treatment with iNO	Baseline, Day 3
Adverse events	Incidence of adverse events = Number of subjects with adverse events/Total number of subjects in treatment×100%	Baseline up to Day 3
Percutaneous arterial oxygen saturation (SpO2)	Change in SpO2 from Baseline after treatment with iNO	Baseline, Day 3

Collaborators and Investigators

• Sponsor: Ting YANG
• Collaborators: Novlead Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2023
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): March 31, 2024

Study Registration Dates

• First Submitted: February 17, 2023
• First Submitted That Met QC Criteria: March 14, 2023
• First Posted (Actual): March 27, 2023

Study Record Updates

• Last Update Posted (Actual): May 15, 2023
• Last Update Submitted That Met QC Criteria: May 12, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Hypertension; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Hypertension, Pulmonary; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antioxidants; Free Radical Scavengers; Endothelium-Dependent Relaxing Factors; Gasotransmitters; Nitric Oxide
• Other Study ID Numbers: 2022-HX-110

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No