Clinical trial NCT04761393: Characterizing Matrix Metalloproteinase-12 (MMP12) in Sputum
Official title: Characterizing Mmp12 In Sputum And Its Relationship To Emphysema And Inflammatory Endotypes
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Emphysema
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Foresee Pharmaceuticals Co., Ltd.
First posted: 2021-02-18
Enrollment: 45
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: This is a cross-sectional study in healthy controls and patients with pulmonary emphysema.

Brief summary: 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.

Detailed 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.

Eligibility 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).

Primary outcomes:
measure: Blood and sputum matrix metalloproteinase-12 (MMP12) levels
timeFrame: Baseline
measure: Quantify their alveolar destruction using Computed Tomography (CT) and magnetic resonance imaging (MRI)
timeFrame: Baseline
measure: Measure other T2 activity biomarkers in sputum
timeFrame: Baseline
measure: Measure other T2 activity biomarkers in sputum supernatant
timeFrame: Baseline
measure: Measure other T2 activity biomarkers in blood
timeFrame: Baseline
measure: Measure other T2 activity biomarkers in blood
timeFrame: Baseline
measure: Compare type-2 (T2) activity biomarkers with healthy individuals in sputum
timeFrame: Baseline
measure: Compare type-2 (T2) activity biomarkers with healthy individuals in blood
timeFrame: Baseline
measure: Compare type-2 (T2) activity biomarkers with healthy individuals in blood
timeFrame: Baseline
measure: Compare type-2 (T2) activity biomarkers with healthy individuals in sputum supernatant
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Firestone Institute for Respiratory Health, St. Joseph's Healthcare
state: Ontario
Study officials:
References:
citation: Shukla Y, Wheatley A, Kirby M, Svenningsen S, Farag A, Santyr GE, Paterson NA, McCormack DG, Parraga G. Hyperpolarized 129Xe magnetic resonance imaging: tolerability in healthy volunteers and subjects with pulmonary disease. Acad Radiol. 2012 Aug;19(8):941-51. doi: 10.1016/j.acra.2012.03.018. Epub 2012 May 15.
citation: Ostridge K, Williams N, Kim V, Bennett M, Harden S, Welch L, Bourne S, Coombs NA, Elkington PT, Staples KJ, Wilkinson TM. Relationship between pulmonary matrix metalloproteinases and quantitative CT markers of small airways disease and emphysema in COPD. Thorax. 2016 Feb;71(2):126-32. doi: 10.1136/thoraxjnl-2015-207428. Epub 2015 Dec 8.
citation: Nair P, Ochkur SI, Protheroe C, Radford K, Efthimiadis A, Lee NA, Lee JJ. Eosinophil peroxidase in sputum represents a unique biomarker of airway eosinophilia. Allergy. 2013 Sep;68(9):1177-84. doi: 10.1111/all.12206. Epub 2013 Aug 9.