- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04761393
Characterizing Matrix Metalloproteinase-12 (MMP12) in Sputum
Characterizing Mmp12 In Sputum And Its Relationship To Emphysema And Inflammatory Endotypes
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Sarah Svenningsen, PhD
- Phone Number: 33024 905-522-1155
- Email: svennins@mcmaster.ca
Study Contact Backup
- Name: Melanie Kjarsgaard
- Phone Number: 33024 905-522-1155
- Email: mkjarsga@stjoes.ca
Study Locations
-
-
Ontario
-
Hamilton, Ontario, Canada, L8N 4A6
- Recruiting
- Firestone Institute for Respiratory Health, St. Joseph's Healthcare
-
Contact:
- Sarah Svenningsen, PhD
- Phone Number: 37313 905-522-1155
- Email: svennins@mcmaster.ca
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
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).
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Cross-Sectional
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Patients with emphysema and eosinophilia in blood and sputum
blood eosinophils ≥300 cells/μL and sputum eosinophils >3%
|
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 paucicellular inflammation
sputum neutrophils <65% and eosinophils <3%
|
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 sputum neutrophilia
sputum neutrophils >65% and sputum eosinophils < 3%
|
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
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Blood and sputum matrix metalloproteinase-12 (MMP12) levels
Time Frame: Baseline
|
Measure sputum and blood MMP12 levels
|
Baseline
|
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. |
Baseline
|
Measure other T2 activity biomarkers in sputum
Time Frame: Baseline
|
Sputum: enumeration of Free eosinophils granules (FEG) by none, few moderate and many
|
Baseline
|
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)
|
Baseline
|
Measure other T2 activity biomarkers in blood
Time Frame: Baseline
|
Ferritin in microgram per litre (ug/L)
|
Baseline
|
Measure other T2 activity biomarkers in blood
Time Frame: Baseline
|
C reactive protein (CRP) in milligram/litre (mg/L)
|
Baseline
|
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.
|
Baseline
|
Compare type-2 (T2) activity biomarkers with healthy individuals in blood
Time Frame: Baseline
|
Ferritin in microgram per litre (ug/L)
|
Baseline
|
Compare type-2 (T2) activity biomarkers with healthy individuals in blood
Time Frame: Baseline
|
C reactive protein (CRP) in milligram/litre (mg/L)
|
Baseline
|
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.
|
Baseline
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Respiratory Tract Diseases
- Lung Diseases
- Disease Attributes
- Lung Diseases, Obstructive
- Pulmonary Disease, Chronic Obstructive
- Chronic Disease
- Pulmonary Emphysema
- Emphysema
- Physiological Effects of Drugs
- Central Nervous System Depressants
- Anesthetics, General
- Anesthetics
- Anesthetics, Inhalation
- Xenon
Other Study ID Numbers
- FIRH_Xe007
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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