Metered Cryospray for the Treatment of Patients With Chronic Obstructive Pulmonary Disease With Chronic Bronchitis

• ClinicalTrials.gov Identifier: NCT03892694
• Recruitment Status: Recruiting
• First Posted: March 27, 2019
• Last Update Posted: April 12, 2021
• Sponsor: CSA Medical, Inc.
• Information provided by (Responsible Party): CSA Medical, Inc.

Study Description

Brief Summary:

To evaluate the relationship between airway structure and function in patients with chronic bronchitis treated with metered cryospray (MCS).

Condition or disease	Intervention/treatment	Phase
COPD; Chronic Bronchitis	Device: RejuvenAir System; Other: Sham	Not Applicable

Detailed Description:

To identify the molecular and cellular targets of MCS treatment and determine the mechanistic relationship to airways remodelling in patients with chronic bronchitis. Phenotype, characterise and correlate clinical, physiological, histological and molecular parameters in patients with chronic bronchitis.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Prospective, multi-centre, randomised, blinded, sham controlled trial with 1:1 randomisation. Sham-control arm subjects are eligible to receive treatment after the 6-month visit.
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Masking Description: Sham controlled.
• Primary Purpose: Treatment
• Official Title: Characterizing the Mechanism of Action of Metered Cryospray for the Treatment of Patients With Chronic Obstructive Pulmonary Disease With Chronic Bronchitis
• Actual Study Start Date: February 14, 2020
• Estimated Primary Completion Date: October 2021
• Estimated Study Completion Date: March 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Treatment; MCS	Device: RejuvenAir System; Bronchial metered cryospray using RejuvenAir® System.
Sham Comparator: Sham Control; Sham	Other: Sham; Sham control procedure

Outcome Measures

Primary Outcome Measures :

1. Goblet cell density [ Time Frame: 6-months post treatment ]
   Difference in change relative to baseline in goblet cell density per mm of basement membrane in endobronchial cryobiopsies at 6-months between treatment and sham-control groups

Secondary Outcome Measures :

1. Histopathological examination of endobronchial cryobiopsies to determine Inflammatory cells and subtype density per mm of basement membrane [ Time Frame: 6-months post treatment ]
   Proportion of inflammatory cells per mm of basement membrane for Neutrophil and Lymphocyte sequencing (RNA-seq)
2. Histopathological examination of endobronchial cryobiopsies to determine epithelial cell density and area (including respiratory epithelial, goblet and basal cells) per mm of basement membrane [ Time Frame: 6-months post treatment ]
   Proportion of epithelial cells per mm of basement membrane for Ciliary and Goblet cells
3. Transcriptomics: Epithelial gene expression as measured by global gene expression sequencing (RNA-seq) [ Time Frame: 6-months post treatment ]
   Transcriptomics: Epithelial gene expression as measured by global gene expression sequencing (RNA-seq)
4. Pulmonary function tests including spirometry, body plethysmography and transfer factors KCO and TLCO [ Time Frame: 6-months post treatment ]
   Pulmonary function tests including spirometry, body plethysmography and transfer factors KCO and TLCO
5. Patient reported outcome measures including SGRQ, mMRC, CAT and Cough Questionnaires [ Time Frame: 6-months post treatment ]
   Patient reported outcome measures including SGRQ, mMRC, CAT and Cough Questionnaires
6. Health care utilisation assessments including number of respiratory exacerbations, emergency room visits, hospital and intensive care unit admissions related to respiratory adverse events [ Time Frame: 6-months post treatment ]
   Health care utilisation assessments including number of respiratory exacerbations, emergency room visits, hospital and intensive care unit admissions related to respiratory adverse events
7. The 6-minute walk tests [ Time Frame: 6-months post treatment ]
   The 6-minute walk tests

Other Outcome Measures:

1. Microvesicle quantification [ Time Frame: 6-months post treatment ]
   Microvesicle quantification
2. Lobar volumes and gas trapping as determined by quantitative CT and parametric response mapping [ Time Frame: 6-months post treatment ]
   Lobar volumes and gas trapping as determined by quantitative CT and parametric response mapping
3. Small airways function as assessed by Impulse Oscillometry (IOS) [ Time Frame: 6-months post treatment ]
   Small airways function as assessed by Impulse Oscillometry (IOS)
4. Composition of epithelial ultrastructure as assessed by transmission electron microscopy [ Time Frame: 6-months post treatment ]
   Composition of epithelial ultrastructure as assessed by transmission electron microscopy

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 79 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Each Subject must meet the following criteria to be enrolled in the study:

1. Males and females ≥40 to <80 years of age.
2. Subject is able to read, understand, and sign a written Informed Consent in order to participate in the study.
3. Subject has a diagnosis of CB and COPD and has been symptomatic for a minimum of two years. (Chronic Bronchitis is defined clinically as chronic productive cough for 3 months in each of 2 successive years in a patient in whom other causes of productive cough have been excluded).
4. Subject is classified as having moderate or severe (GOLD stage 2-3) airflow obstruction defined by a post-bronchodilator of =>30% FEV1 to <80% predicted with a baseline FEV1/FVC of <0.70.
5. Subject has a COPD assessment tool (CAT) score of ≥10.
6. Subject is being treated according to current medically accepted treatment guidelines without successful resolution of chronic bronchitis and agrees to continue maintenance pulmonary/COPD medications (as defined per GOLD Standard for medications) for the duration of the study (subject must be on a regime of pulmonary medications for a minimum of 2 weeks prior to enrolment into the study).
7. Smoking history of at least 10 pack years.
8. Non-smoking for a minimum of 2 months prior to consent and agrees to continue not smoking for the duration of the study.
9. Subject is able to adhere to and undergo 4 bronchoscopic procedures (5 for control subjects accepting cross over option), in the opinion of the investigator or per hospital guidelines.
10. For women of childbearing potential: non-pregnant, non-lactating, and agree to practice an adequate birth control method (abstinence, combination barrier and spermicide, or hormonal) for the duration of the study.

Exclusion Criteria:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

1. Subject has had an acute pulmonary infection, exacerbation or pneumonia requiring medical treatment (with antibiotics and/or steroids) within 6 weeks of initially planned study bronchoscopy.
2. Diagnosis of asthma with an onset before 30 years of age.
3. Subject has Alpha-1 antitrypsin deficiency.
4. Subject has other origins of respiratory disease aside from chronic bronchitis and COPD.
5. Subject is using e-cigarettes, vaping or taking any oral or inhaled substances not prescribed by a physician.
6. Subject has untreatable or life-threatening arrhythmias, or history of inability to adequately oxygenate during a bronchoscopy, or has acute respiratory failure with hypercapnia.
7. Subject has bullous emphysema characterized as large bullae >30 millimetres on HRCT; or subject has stenosis in the tracheobronchial system, tracheobronchomegaly, trachea-bronchomalacia, amyloidosis or cystic fibrosis.
8. Subject has clinically significant bronchiectasis
9. Subject has had a transplant procedure (any).
10. Subject has a known mucosal tear, has undergone prior lung surgery such as pneumonectomy, lobectomy, bullectomy, or lung volume reduction surgery, bronchial thermoplasty, rheoplasty or cryotherapy.
11. Subject has had a prior lung device procedure, including emphysema stent(s) implanted, lung coils, valves, lung denervation or other devices for emphysema.
12. Subject is unable to temporarily discontinue use of anticoagulant therapy: warfarin, Coumadin, LMWH, heparin, clopidrogel (or equal).
13. Subject has a serious medical condition, such as: uncontrolled coagulopathy or bleeding disorder, congestive heart failure, uncontrolled angina, myocardial infarction in the past year, renal failure, liver disease, cerebrovascular accident within the past 6 months, uncontrolled diabetes, uncontrolled hypertension, autoimmune disease or uncontrolled gastric reflux.
14. Subject has or is receiving chemotherapy or active radiation therapy within the past 6 months or is expected to receive chemotherapy during participation in this study.
15. Subject is or has been in another clinical investigational study within 6 weeks of enrolment.
16. Subject has known sensitivity to medication required to perform bronchoscopy (such as lidocaine, atropine, and benzodiazepines).

Contacts and Locations

Contacts

Contact: Heather Nigro; 781-538-4793; hnigro@csamedical.com

Contact: Joyce Musacchio; 781-538-4794; jmusacchio@csamedical.com

Locations

Netherlands

University Medical Center Groningen; Recruiting

Groningen, Netherlands

Contact: Karin Klooster, PhD 0031-646-03226 k.klooster@umcg.nl

Principal Investigator: Dirk-Jan Slebos, MD

United Kingdom

The Royal Brompton Hospital; Recruiting

London, United Kingdom, SW3 6NP

Contact: Christopher Orton, MD 02073518029 C.Orton@rbht.nhs.uk

Principal Investigator: Pallav Shah, MD

Sponsors and Collaborators

CSA Medical, Inc.

Investigators

• Principal Investigator: Pallav Shah, MD; The Royal Brompton Hospital

More Information

• Responsible Party: CSA Medical, Inc.
• ClinicalTrials.gov Identifier: NCT03892694
• Other Study ID Numbers: 022
• First Posted: March 27, 2019
• Last Update Posted: April 12, 2021
• Last Verified: April 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Bronchitis; Bronchitis, Chronic; Acute Disease; Lung Diseases; Respiratory Tract Diseases; Bronchial Diseases; Respiratory Tract Infections; Disease Attributes; Pathologic Processes