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

February 22, 2024 updated by: CSA Medical, Inc.

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

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

Study Overview

Status

Active, not recruiting

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 Type

Interventional

Enrollment (Estimated)

32

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Groningen, Netherlands
        • University Medical Center Groningen
      • London, United Kingdom, SW3 6NP
        • The Royal Brompton Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 79 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Sham Comparator: Sham Control
Sham
Sham control procedure
Active Comparator: Treatment
MCS
Bronchial metered cryospray using RejuvenAir® System.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
6-months post treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
6-months post treatment
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
6-months post treatment
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)
6-months post treatment
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
6-months post treatment
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-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
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
6-months post treatment
The 6-minute walk tests
Time Frame: 6-months post treatment
The 6-minute walk tests
6-months post treatment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Microvesicle quantification
Time Frame: 6-months post treatment
Microvesicle quantification
6-months post treatment
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
6-months post treatment
Small airways function as assessed by Impulse Oscillometry (IOS)
Time Frame: 6-months post treatment
Small airways function as assessed by Impulse Oscillometry (IOS)
6-months post treatment
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
6-months post treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 14, 2020

Primary Completion (Actual)

July 11, 2022

Study Completion (Estimated)

June 1, 2024

Study Registration Dates

First Submitted

March 26, 2019

First Submitted That Met QC Criteria

March 26, 2019

First Posted (Actual)

March 27, 2019

Study Record Updates

Last Update Posted (Estimated)

February 23, 2024

Last Update Submitted That Met QC Criteria

February 22, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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