Characterizing Matrix Metalloproteinase-12 (MMP12) in Sputum

Recruiting

• Conditions: Emphysema
• Interventions: Procedure: Hyperpolarized 129Xe (Xenon) diffusion-weighted MRI

• Registration Number: NCT04761393
• Lead Sponsor: McMaster University

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.

Study Timeline

• Study First Submitted: 2021-02-11
• Study First Submitted QC: 2021-02-17
• Study First Posted: 2021-02-18
• Study Start: 2022-11-29
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-18
• Last Update Posted: 2024-11-20
• Primary Completion: 2025-01
• Study Completion: 2025-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

Not provided

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).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients with emphysema and sputum neutrophilia	Hyperpolarized 129Xe (Xenon) diffusion-weighted MRI	sputum neutrophils \>65% and sputum eosinophils \< 3%
Patients with emphysema and eosinophilia in blood and sputum	Hyperpolarized 129Xe (Xenon) diffusion-weighted MRI	blood eosinophils ≥300 cells/μL and sputum eosinophils \>3%
Patients with emphysema and paucicellular inflammation	Hyperpolarized 129Xe (Xenon) diffusion-weighted MRI	sputum neutrophils \<65% and eosinophils \<3%

Primary Outcome Measures

Name	Time	Method
Measure other T2 activity biomarkers in sputum	Baseline	Sputum: enumeration of Free eosinophils granules (FEG) by none, few moderate and many
Measure other T2 activity biomarkers in sputum supernatant	Baseline	Sputum supernatant: Levels of (interleukin) IL-4, IL-5 and IL-13, eosinophil peroxidase, transforming growth factor (TGF)-beta, Phospho-Smad2 and Phospho-Smad3 (SMAD=Small Mothers Against Decapentaplegic gene)
Measure other T2 activity biomarkers in blood	Baseline	C reactive protein (CRP) in milligram/litre (mg/L)
Compare type-2 (T2) activity biomarkers with healthy individuals in sputum supernatant	Baseline	Sputum supernatant: Levels of IL-4, IL-5 and IL-13, eosinophil peroxidase, TGF-beta, Phospho-Smad2 and Phospho-Smad3.
Quantify their alveolar destruction using Computed Tomography (CT) and magnetic resonance imaging (MRI)	Baseline	The relative area of the Computed Tomography (CT) attenuation histogram with attenuation of 950 HU or less (RA950) and the 15th percentile of the CT attenuation histogram (HU15) will be generated to quantify emphysema.; For analysis of 129Xe diffusion-weighted MR images we will employ the same approach as described by Kirby and colleagues to quantify the apparent diffusion coefficient (ADC) and generate ADC maps12 to assess airspace size.
Compare type-2 (T2) activity biomarkers with healthy individuals in sputum	Baseline	Sputum: enumeration of Free eosinophils granules (FEG) as few, moderate and many.
Blood and sputum matrix metalloproteinase-12 (MMP12) levels	Baseline	Measure sputum and blood MMP12 levels
Compare type-2 (T2) activity biomarkers with healthy individuals in blood	Baseline	C reactive protein (CRP) in milligram/litre (mg/L)

Trial Locations

Locations (1)

Firestone Institute for Respiratory Health, St. Joseph's Healthcare; 🇨🇦 Hamilton, Ontario, Canada