A Clinical Study of Inhaled Nitric Oxide in Moderate-to-Severe Chronic Obstructive Pulmonary Disease (NOVEL)

Efficacy and Safety of Inhaled Nitric Oxide in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease: a Prospective, Single-center Clinical Trial

The purpose of this study is to evaluate the influence of exercise capacity and safety of iNO at doses of 10 ppm or 40 ppm for 2 hours per day after continuous treatment for one week, which is of great significance for finding safe and effective methods for treating COPD.

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Linfu Zhou, Doctor; Phone Number: +8613611573618; Email: linfu.zhou@126.com
• Study Contact Backup: Name: Liuchao Zhang, Master; Phone Number: +8615850423930

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Recruiting
      • The First Affiliated Hospital with Nanjing Medical University
      • Contact: Linfu Zhou, Doctor; Phone Number: +8613611573618; Email: linfu.zhou@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 40 years, ≤ 75 years;
2. Previous smoking history ≥ 10 pack-years, and had stopped smoking for one month before study entry;
3. Met the diagnosis criteria of moderate and severe COPD: a post-bronchodilator FEV1/FVC < 0.7, and 30%< FEV1 < 80% predicted;
4. Signed informed consent and performed all the study mandated procedures.

Exclusion Criteria:

1. Pregnant or lactating women;
2. Current or recent month user of nicotine-like substances (including nicotine patches, etc.);
3. A diagnosis of asthma or other non-COPD respiratory disease, in the opinion of the Investigator;
4. Lack of patency of nares upon physical examination;
5. Experienced during the last month an exacerbation requiring start of or increase in systemic oral corticosteroid therapy;
6. Left ventricular systolic dysfunction: left ventricular ejection fraction (LVEF) < 50%;
7. Clinically significant valvular heart disease, including aortic valvular disease (moderate or severe aortic stenosis or regurgitation) and/or mitral valve disease (moderate or severe mitral stenosis or regurgitation), or status post mitral valve replacement;
8. Use within 30 days of screening or current use of approved pulmonary hypertension medications such as sildenafil, bosentan or prostacyclines;
9. Use of investigational drugs or devices within 30 days prior to enrollment into the study;
10. 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: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low concentration group; inhaled nitric oxide (iNO) 10ppm，≥2 hours/day for 7 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.
Experimental: High concentration group; iNO 40ppm，≥2 hours/day for 7 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
Cardiopulmonary Exercise Test: Maximal oxygen uptake（VO2max）	Change in VO2max from Baseline after treatment with iNO	Baseline, Day 7
Cardiopulmonary Exercise Test: Minute ventilation-to-carbon dioxide output（VE/VCO2）	Change in VE/VCO2 from Baseline after treatment with iNO	Baseline, Day 7
Cardiopulmonary Exercise Test: Borg score	Change in Borg score from Baseline after treatment with iNO	Baseline, Day 7
Cardiopulmonary Exercise Test: oxygen uptake/work (△VO2/△W) ratio	Change in △VO2/△W ratio from Baseline after treatment with iNO	Baseline, Day 7

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 7
Pulmonary function: Forced vital capacity （FVC）	Change in FVC from Baseline after treatment with iNO	Baseline, Day 7
Pulmonary function：FEV1/FVC	Change in FEV1/FVC from Baseline after treatment with iNO	Baseline, Day 7
Life quality and symptom 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 7
Life quality and symptom 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 7
Six-minute walk test	Change in exercise capacity from Baseline after treatment with iNO: the distance of six-minute walk test	Baseline, Day 7
Adverse events	Incidence of adverse events = Number of subjects with adverse events/Total number of subjects in treatment×100%	Baseline up to Day 7

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Collaborators: Novlead Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2023
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: June 1, 2023
• First Submitted That Met QC Criteria: June 1, 2023
• First Posted (Actual): June 9, 2023

Study Record Updates

• Last Update Posted (Estimated): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Chronic Disease; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; 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: 2023-COPD-002

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