Primary:• To evaluate the safety of RejuvenAir Cryospray therapy to treat symptomatic chronic bronchitis patients with airflow restrictions• To evaluate the feasibility of the planned liquid nitrogen cryospray treatment.Secondary:• To evaluate…
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary:
• Adverse and serious adverse events.
• Application of 75% or greater of the intended MCS to the desired locations in
up to three sequential bronchoscopies.
Secondary outcome
Secondary:
• Histologic appearance of bronchial biopsies in Phase A subjects
• Airway wall thickness using high resolution computed tomography (HRCT)
Exploratory:
• Signs and symptoms of Chronic Bronchitis (production of cough, production of
sputum, sense of breathlessness)
• Patient Reported Outcome Instruments (SGRQ, , VAS, CAT, mMRC)
• Spirometry Testing (FEV1,FEV1/FVC,VC, FIV1)
• RAW
• 6 MWT
• High Resolution computed tomography (HRCT)
• Serum Fibrinogen
Background summary
Chronic bronchitis (CB) is a chronic inflammation of the airways that occurs
most commonly in response to cigarette smoking but can also be induced by
exposure to noxious particles or gases.In CB subjects the airway inflammation
and irritation causes epithelial remodeling and
metaplasia that leads to a loss of ciliated cells into metaplastic goblet cells
that overpopulate the bronchial epithelium.
Although there are medications that focus on decreasing the inflammation such
as inhaled and oral corticosteroids and both beta-adrenergic agonists and
anticholinergics to attempt to reverse the bronchial wall swelling and relax
the airway walls, no current medication exists to contra-act the goblet cell
mucous production.We propose to use the RejuvenAir System, a cryosurgical
device that applies medical grade liquid nitrogen to the bronchial airways via
a radial head catheter, to treat the bronchial epithelium directly ablating the
abnormal metaplastic epithelium allowing regeneration of normal bronchial
epithelium.
Study objective
Primary:
• To evaluate the safety of RejuvenAir Cryospray therapy to treat symptomatic
chronic bronchitis patients with airflow restrictions
• To evaluate the feasibility of the planned liquid nitrogen cryospray
treatment.
Secondary:
• To evaluate evidence of healing effect after the therapy in all Phase A
subjects
• To evaluate the effect of therapy on airway wall thickness using high
resolution computed tomography (HRCT) before and after completion of treatment.
Exploratory
• To evaluate the effect of therapy on patient related signs and symptoms of
their chronic bronchitis.
• To evaluate the effect of therapy on patient reported outcome measurements of
chronic bronchitis.
• To evaluate the effect of therapy on objective measures of chronic bronchitis
Study design
Prospective, open label, single arm study with sequential accrual of subjects
with known chronic bronchitis.
There are two phases to this study. Phase A will enroll up to 12 subjects and
will treat a single lobe to assess safety, feasibility and
histology/immunology. After review of the data by the Data Safety Monitoring
Board, Phase B of the study would begin. In Phase B of the study, Phase A
subjects would have their remaining two lobes treated. In addition up to 24
subjects will be enrolled and will have all upper and lower lobes treated to
assess safety, feasibility and immunology.
Intervention
In phase A of the study, up to 12 subjects will undergo treatment of the right
lower lobe and right main stem bronchus. Each MCS will be tailored to the
bronchial area undergoing treatment and the amount of liquid nitrogen delivered
will vary depending on the airway diameter.
In phase B of the study, phase A subjects will receive treatment to the left
lower lobe and associated left main stem followed 30 to 45 days later by a
third treatment to both upper lobes, and any untreated main stem bronchus and
base of trachea. In addition, up to 24 subjects will be enrolled and will have
three treatments that will cover the same areas with a 30 to 45 day wait
between the first and second and then second and third treatment session.
Study burden and risks
It is expected that this study may be of direct benefit to the subject. While
there is no guarantee of any results or outcomes it is possible that subjects
may show signs ofimprovement of their chronic bronchitis symptoms such as
cough, sputum production and sense of breathlessness or well-being. The
information learned from this study will be important for the future
development of a bronchoscopic treatment for subjects with bronchial airway
conditions in which the airway lining is impaired. In particular, the
information will be used to inform the development of the RejuvenAir System as
a safe and effective treatment option for subjects with chronic diseases of the
airways, such as chronic bronchitis. The risks from this study include those
generally associated with bronchoscopy. Bronchoscopy is currently performed in
normal and diseased subjects to obtain biopsies of the airways for which
subjects may not realize direct benefit, but rather contribute to the
scientific understanding of airway diseases. The risk associated with the
treatment are a risk of airway or lung perforation, pneumothorax, or
pneumomediastinum, bradycardia in subjects undergoing LN metered cryospray due
to the need for the expanding nitrogen gas created from the dissipation of the
liquid nitrogen to its gaseous state. Longer term, there may be a risk of
airway stricture in the area of airway tissue
healing.
Hartwell Avenue 91
Lexington MA 02421
US
Hartwell Avenue 91
Lexington MA 02421
US
Listed location countries
Age
Inclusion criteria
• Males and females >=40 to <=75 years of age.
• Subject is able to read, understand, and sign a written Informed Consent.
• Subject agrees to continue maintenance pulmonary/COPD medications for the
duration of the study.
• Diagnosis of chronic bronchitis (CB) and chronic obstructive pulmonary disease
(COPD) 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.)
• Pre-procedure post bronchodilator FEV1 of greater than or equal to 30% and less
than or equal to 80% of predicted within 3 months of enrollment.
• Smoking history of at least 10 pack years.
• Non-smoking for a minimum of 6 months prior to consent and agrees to continue
not smoking for the duration of the study.
• Subject is able to adhere to and undergo 3 (4 if in Phase A) bronchoscope
procedures that includes lung biopsies and multiple MCS treatments in the
opinion of the investigator or per hospital guidelines. (Only Phase A subjects
receive biopsies)
Exclusion criteria
• Subject has had an acute pulmonary infection or pneumonia within prior 6 weeks
of study bronchoscopy.
• Subject has had a CB and/or COPD exacerbation (requiring steroids and/or
antibiotics) within 6 weeks prior to study bronchoscopy, as defined by their
treating physician
• Subject has clinically significant bronchiectasis or other respiratory disease other
than chronic bronchitis and COPD.
• Diagnosis of asthma with an onset before 30 years of age
• Subject has bullous emphysema characterized as large bullae >30 millimeters on
CT.
• Subject has had a transplant.
• Subject has the inability to walk >140 meters
• Subject has PaC02 >8kPa, or a PaO2<7kPa at room air.
• Subject has a RVSP >45mmHg or a LVEF<45% on 2D-cardiac echo.
• Subject has undergone lung surgery: pneumonectomy, lobectomy, bullectomy,
lung volume reduction surgery
• Subject has had a prior lung device procedure, including emphysema stent(s)
implanted, lung coils, valves, lung denervation or other devices for emphysema.
• Subject is unable to temporarily discontinue use of anticoagulant therapy:
warfarin, Coumadin, LMWH, heparin, clopidrogel (or equal)
• Subject is on >10 mg of prednisolone/day.
• Subject has a serious medical condition, such as: uncontrolled congestive heart
failure, uncontrolled angina, myocardial infarction in the past year, renal failure,
liver disease, cerebrovascular accident within the past 6 months, uncontrolled
diabetes, hypertension, autoimmune disease or uncontrolled gastric reflux
• Subject is pregnant, nursing, or planning to get pregnant during study duration.
• Subject has received chemotherapy within the past 6 months or is expected to
receive chemotherapy during participation in this study.
• Subject is or has been in another clinical investigational study within 6 weeks of
baseline.
• Subject has known sensitivity to medication required to perform bronchoscopy
(such as lidocaine, atropine, and benzodiazepines).
• Subject has been in another clinical investigational study within 6 weeks of
baseline.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02483637 |
| CCMO | NL54098.042.15 |