Characterizing Matrix Metalloproteinase-12 (MMP12) in Sputum

McMaster University

Status

Enrolling

Conditions

Emphysema

Treatments

Procedure: Hyperpolarized 129Xe (Xenon) diffusion-weighted MRI

Study type

Observational

Funder types

Other

Industry

Identifiers

NCT04761393

FIRH_Xe007

Details and patient eligibility

About

The hypothesis is that in patients with emphysema, a high MMP12 sputum and/or blood level correlates with airspace enlargement and with increased sputum Th2 immune biomarkers.

Full description

Since MMP-12 apparently has a preponderant role in the genesis of emphysema and probably in airspace enlargement, its inhibition may result in an interesting targeting point in view to find specific therapies in obstructive diseases. There is abundant evidence in animal models that shows how MMP-12 blockade inhibits the development of emphysema and airway remodeling. Unfortunately, the results have not been conclusive in human models.

In the last years, pulmonary imaging biomarkers that measure airspace enlargement have been developed. In particular, the apparent diffusion coefficient (ADC), quantified by inhaled hyperpolarized gas MRI, reflects alveolar airspace size. ADC provides information consistent with histopathological findings that may be used to estimate lung disease progression and treatment response.

Enrollment

45 estimated patients

Sex

All

Ages

40 to 85 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria (COPD):

≥40 years of age
Current or ex-smokers with a >10 pack year smoking history
Have a post-bronchodilator forced expired volume in 1 second (FEV1)/forced expired vital capacity (FVC) ratio of <70% and a post-bronchodilator FEV1 value from ≥30% predicted (GOLD 1, 2 and 3), (Global Initiative for Obstructive Lung disease)
Have a radiologist confirmed pulmonary emphysema diagnosis based on CT

Inclusion criteria for normal controls:

No clinically significant medical condition or a history of asthma, COPD, cystic fibrosis, or other significant respiratory disorder including significant occupational or environmental exposures with ongoing respiratory symptoms.
No current or past smoking history
Have a post-bronchodilator FEV1/FVC ratio of >70%

Exclusion Criteria:

Any potential subject who meets any of the following criteria will be excluded from participating in the study:

Patients with other non-COPD airway diseases
Patients with very severe COPD (FEV1<30% predicted)
Patients with an intercurrent exacerbation
Patients with life expectancy less than 3 months
Pregnant or breastfeeding
Undergoing immunomodulatory or biologic treatment
Use of systemic steroids in the last month
Hospitalization in the last 12 months due to exacerbation
Known cardiovascular comorbidity under treatment or with hospitalizations of this cause in the last year
That they cannot perform spirometry
Active malignancy
Realization of lung surgery during the study period
History of alcohol and drug abuse that prevents compliance with follow-up
History of bronchial thermoplasty
Participating in another study concomitantly
MRI Related: patients who have implanted mechanically, electrically or magnetically activated device or any metal in their body which cannot be removed, including but not limited to pacemakers, artificial limb, metallic fragments of foreign body, shunt, surgical staples (including clips or metallic sutures and/or ear implants).