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NCT Number: NCT04761393

Characterizing Matrix Metalloproteinase-12 (MMP12) in Sputum

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.

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Key information

Conditions

Emphysema Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

40 year–85 year

Sex eligibility

All sexes

Study type

Observational

Primary location

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

Hamilton, Ontario, L8N 4A6, Canada

Location status: Recruiting

Location contact

Sarah Svenningsen, PhD

CONTACT

[email protected]

905-522-1155 ext. 37313

About this study

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.

Who can participate

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

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

Primary outcomes

  1. Blood and sputum matrix metalloproteinase-12 (MMP12) levels

    Time frame: Baseline

    Measure sputum and blood MMP12 levels

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

    Time frame: 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.

  3. Measure other T2 activity biomarkers in sputum

    Time frame: Baseline

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

  4. Measure other T2 activity biomarkers in sputum supernatant

    Time frame: 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)

  5. Measure other T2 activity biomarkers in blood

    Time frame: Baseline

    Ferritin in microgram per litre (ug/L)

  6. Measure other T2 activity biomarkers in blood

    Time frame: Baseline

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

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

    Time frame: Baseline

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

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

    Time frame: Baseline

    Ferritin in microgram per litre (ug/L)

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

    Time frame: Baseline

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

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

    Time frame: Baseline

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

Study contacts

Contact information is provided by the study sponsor or research team.

Melanie Kjarsgaard

CONTACT

[email protected]

905-522-1155 ext. 33024

Sarah Svenningsen, PhD

CONTACT

[email protected]

905-522-1155 ext. 33024

Sponsors and collaborators

Lead sponsor

McMaster University

Other

Collaborators

  • Foresee Pharmaceuticals Co., Ltd.

Registry information

Official study title

Characterizing Mmp12 In Sputum And Its Relationship To Emphysema And Inflammatory Endotypes

Important dates

Study start
2022
Primary completion
2025
Study completion
2025
First posted
Feb 18, 2021
Registry last updated
Nov 20, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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