EmphysemaNCT04761393
Characterizing Matrix Metalloproteinase-12 (MMP12) in Sputum
An observational study of Emphysema, run by McMaster University at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 85 years
- Conditions the study is for
- Emphysema
- What is being tested?
- Hyperpolarized 129Xe (Xenon) diffusion-weighted MRI
- Type of treatment
- Surgery or procedure
- How many people
- 45 participants
- Where
- 1 siteCanada
- Study dates
- 29 Nov 2022to Jan 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 85 years
- All sexes
- Adult, Older adult
Study population: This is a cross-sectional study in healthy controls and patients with pulmonary emphysema.
Who may be able to join
- ≥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%
Who cannot join
- 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
Show all 17Show fewer
- 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Firestone Institute for Respiratory Health, St. Joseph's Healthcare
Hamilton, Ontario, L8N 4A6
Sarah Svenningsen, PhD, 905-522-1155 ext. 37313, svennins@mcmaster.ca
About this study
Official title: Characterizing Mmp12 In Sputum And Its Relationship To Emphysema And Inflammatory Endotypes
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.
Read the 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.
- Conditions
- Emphysema
- Being tested
- Hyperpolarized 129Xe (Xenon) diffusion-weighted MRI
- Medical subject headings
- Emphysema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyperpolarized 129Xe (Xenon) diffusion-weighted MRIProcedure or surgery
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
| Study group | Role | What they receive |
|---|---|---|
| Patients with emphysema and eosinophilia in blood and sputum | blood eosinophils ≥300 cells/μL and sputum eosinophils >3% Receives: Procedure: Hyperpolarized 129Xe (Xenon) diffusion-weighted MRI | |
| Patients with emphysema and paucicellular inflammation | sputum neutrophils <65% and eosinophils <3% Receives: Procedure: Hyperpolarized 129Xe (Xenon) diffusion-weighted MRI | |
| Patients with emphysema and sputum neutrophilia | sputum neutrophils >65% and sputum eosinophils < 3% Receives: Procedure: Hyperpolarized 129Xe (Xenon) diffusion-weighted MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood and sputum matrix metalloproteinase-12 (MMP12) levels
Measure sputum and blood MMP12 levels
Measured: 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.
Measured: Baseline
Measure other T2 activity biomarkers in sputum
Sputum: enumeration of Free eosinophils granules (FEG) by none, few moderate and many
Measured: 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)
Measured: Baseline
Measure other T2 activity biomarkers in blood
Ferritin in microgram per litre (ug/L)
Measured: Baseline
Measure other T2 activity biomarkers in blood
C reactive protein (CRP) in milligram/litre (mg/L)
Measured: Baseline
Compare type-2 (T2) activity biomarkers with healthy individuals in sputum
Sputum: enumeration of Free eosinophils granules (FEG) as few, moderate and many.
Measured: Baseline
Compare type-2 (T2) activity biomarkers with healthy individuals in blood
Ferritin in microgram per litre (ug/L)
Measured: Baseline
Compare type-2 (T2) activity biomarkers with healthy individuals in blood
C reactive protein (CRP) in milligram/litre (mg/L)
Measured: 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.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2021
- Study start29 Nov 2022
- Primary completionJan 2025 (estimated)
- Study completionJan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for EmphysemaStudies of the same condition, open and under way.
- More trials run by McMaster UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Collaborators
- Foresee Pharmaceuticals Co., Ltd.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04761393
- Sponsor's protocol ID
- FIRH_Xe007
- Status last verified
- Nov 2024
- First submitted
- 11 Feb 2021
- Last updated
- 20 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
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.
PubMed 22591724Ostridge 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.
PubMed 26645414Nair 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.
PubMed 23931643
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterizing Mmp12 In Sputum And Its Relationship To Emphysema And Inflammatory Endotypes
- ClinicalTrials.gov ID
- NCT04761393
- Acronym / sponsor ID
- FIRH_Xe007
- Conditions
- Emphysema
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Collaborators
- Foresee Pharmaceuticals Co., Ltd.
- Study start
- 29 Nov 2022 (actual)
- Primary completion
- Jan 2025 (estimated)
- Study completion
- Jan 2025 (estimated)
- First posted
- 18 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Patients with emphysema and eosinophilia in blood and sputum | – | Procedure: Hyperpolarized 129Xe (Xenon) diffusion-weighted MRIblood eosinophils ≥300 cells/μL and sputum eosinophils >3% |
| Patients with emphysema and paucicellular inflammation | – | Procedure: Hyperpolarized 129Xe (Xenon) diffusion-weighted MRIsputum neutrophils <65% and eosinophils <3% |
| Patients with emphysema and sputum neutrophilia | – | Procedure: Hyperpolarized 129Xe (Xenon) diffusion-weighted MRIsputum neutrophils >65% and sputum eosinophils < 3% |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- This is a cross-sectional study in healthy controls and patients with pulmonary emphysema.
Key inclusion criteria (7 listed)
- ≥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.
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hyperpolarized 129Xe (Xenon) diffusion-weighted MRIParticipants 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 | Procedure or surgery | Patients with emphysema and eosinophilia in blood and sputum, Patients with emphysema and paucicellular inflammation, Patients with emphysema and sputum neutrophilia |
Primary outcome
Blood and sputum matrix metalloproteinase-12 (MMP12) levels
Time frame: Baseline
Measure sputum and blood MMP12 levels
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.
Measure other T2 activity biomarkers in sputum
Time frame: Baseline
Sputum: enumeration of Free eosinophils granules (FEG) by none, few moderate and many
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)
Measure other T2 activity biomarkers in blood
Time frame: Baseline
Ferritin in microgram per litre (ug/L)
Measure other T2 activity biomarkers in blood
Time frame: Baseline
C reactive protein (CRP) in milligram/litre (mg/L)
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.
Compare type-2 (T2) activity biomarkers with healthy individuals in blood
Time frame: Baseline
Ferritin in microgram per litre (ug/L)
Compare type-2 (T2) activity biomarkers with healthy individuals in blood
Time frame: Baseline
C reactive protein (CRP) in milligram/litre (mg/L)
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2024.
- Background: PubMed 22591724Shukla 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.
- Background: PubMed 26645414Ostridge 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.
- Background: PubMed 23931643Nair 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Emphysema, run by McMaster University at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sarah Svenningsen, PhD (905-522-1155 ext. 33024, svennins@mcmaster.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood and sputum matrix metalloproteinase-12 (MMP12) levels (time frame: Baseline). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04761393, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2024.