Characterizing Matrix Metalloproteinase-12 (MMP12) in Sputum

NCT04761393 | Recruiting

• 1 other identifier: FIRH_Xe007
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Emphysema

Outcome Measures

Primary Outcomes (10)

• Blood and sputum matrix metalloproteinase-12 (MMP12) levels

  Measure sputum and blood MMP12 levels

  Baseline

• Quantify their alveolar destruction using Computed Tomography (CT) and magnetic resonance imaging (MRI)

  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.

  Baseline

• Measure other T2 activity biomarkers in sputum

  Sputum: enumeration of Free eosinophils granules (FEG) by none, few moderate and many

  Baseline

• Measure other T2 activity biomarkers in sputum supernatant

  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)

  Baseline

• Measure other T2 activity biomarkers in blood

  Ferritin in microgram per litre (ug/L)

  Baseline

• Measure other T2 activity biomarkers in blood

  C reactive protein (CRP) in milligram/litre (mg/L)

  Baseline

• Compare type-2 (T2) activity biomarkers with healthy individuals in sputum

  Sputum: enumeration of Free eosinophils granules (FEG) as few, moderate and many.

  Baseline

• Compare type-2 (T2) activity biomarkers with healthy individuals in blood

  Ferritin in microgram per litre (ug/L)

  Baseline

• Compare type-2 (T2) activity biomarkers with healthy individuals in blood

  C reactive protein (CRP) in milligram/litre (mg/L)

  Baseline

• Compare type-2 (T2) activity biomarkers with healthy individuals in sputum supernatant

  Sputum supernatant: Levels of IL-4, IL-5 and IL-13, eosinophil peroxidase, TGF-beta, Phospho-Smad2 and Phospho-Smad3.

  Baseline

Study Arms (3)

Patients with emphysema and eosinophilia in blood and sputum

blood eosinophils ≥300 cells/μL and sputum eosinophils \>3%

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

Patients with emphysema and paucicellular inflammation

sputum neutrophils \<65% and eosinophils \<3%

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

Patients with emphysema and sputum neutrophilia

sputum neutrophils \>65% and sputum eosinophils \< 3%

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

Interventions

Hyperpolarized 129Xe (Xenon) diffusion-weighted MRI PROCEDURE

Participants will inhale a one litre gas mixture containing hyperpolarized 129Xe mixed with nitrogen (N2) or helium (4He) from a one litre dose bag. Breath-hold will be up to 16 seconds

Patients with emphysema and eosinophilia in blood and sputum; Patients with emphysema and paucicellular inflammation; Patients with emphysema and sputum neutrophilia

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

This is a cross-sectional study in healthy controls and patients with pulmonary emphysema.

You may qualify if:

• ≥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
• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• McMaster University: lead
• Foresee Pharmaceuticals Co., Ltd.: collaborator

Study Sites (1)

Firestone Institute for Respiratory Health, St. Joseph's Healthcare

Hamilton, Ontario, L8N 4A6, Canada

RECRUITING

Related Publications (3)

• 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.

  PMID: 22591724 BACKGROUND

• 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.

  PMID: 26645414 BACKGROUND

• 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.

  PMID: 23931643 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Sputum

MeSH Terms

Conditions

Emphysema

Interventions

Xenon

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Noble Gases; Elements; Inorganic Chemicals; Gases

Central Study Contacts

Sarah Svenningsen, PhD

CONTACT

905-522-1155; svennins@mcmaster.ca

Melanie Kjarsgaard

CONTACT

905-522-1155; mkjarsga@stjoes.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2021
• First Posted: February 18, 2021
• Study Start: November 29, 2022
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: November 20, 2024

Record last verified: 2024-11

Locations

CA (1)