Characterizing Matrix Metalloproteinase-12 (MMP12) in Sputum

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Процедура Hyperpolarized 129Xe (Xenon) diffusion-weighted MRI
  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

Первичные конечные точки

• Blood and sputum matrix metalloproteinase-12 (MMP12) levels [Срок оценки: Baseline]
• Quantify their alveolar destruction using Computed Tomography (CT) and magnetic resonance imaging (MRI) [Срок оценки: Baseline]
• Measure other T2 activity biomarkers in sputum [Срок оценки: Baseline]
• Measure other T2 activity biomarkers in sputum supernatant [Срок оценки: Baseline]
• Measure other T2 activity biomarkers in blood [Срок оценки: Baseline]
• Measure other T2 activity biomarkers in blood [Срок оценки: Baseline]
• Compare type-2 (T2) activity biomarkers with healthy individuals in sputum [Срок оценки: Baseline]
• Compare type-2 (T2) activity biomarkers with healthy individuals in blood [Срок оценки: Baseline]
• Compare type-2 (T2) activity biomarkers with healthy individuals in blood [Срок оценки: Baseline]
• Compare type-2 (T2) activity biomarkers with healthy individuals in sputum supernatant [Срок оценки: Baseline]

Критерии участия

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%

Критерии исключения

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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Канада · 1 центр

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

Публикации

• 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
• 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
• 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

Идентификаторы

NCT: NCT04761393 · FIRH_Xe007

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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