Asthma; EosinophilicFUNLUMNCT04512521
Functional Lung MRI for Early Treatment Response Assessment for Patients With Eosinophilic Asthma
An observational study of Asthma; Eosinophilic, run by Hannover Medical School at 1 site in Germany.
Trial summary
Patients with severe eosinophilic asthma will be placed on biologics if they continue to be uncontrolled despite maximized inhalation therapy or if they are only controlled under oral corticosteroids. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Asthma; Eosinophilic
- What is being tested?
- Mepolizumab
- How many people
- 40 participants
- Where
- 1 siteGermany
- Study dates
- 4 May 2020to Aug 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The patients will be selected for this study consecutively by Dr. Suhling (or colleagues; Dr. Drick) from his Asthma outpatient clinic according to his clinical judgement.
Who may be able to join
- Able and willing to give written informed consent.
- Male and female subjects, aged ≥ 18 years.
- Patients which are eligible for treatment using anti-IL-5 -antibody treatment following guidelines: severe eosinophilic asthma and blood eosinophils of ≥150 cells/μL at screening or ≥ 300 cells/μL within 12 months prior to treatment
- Physician-diagnosed severe asthma according to ERS/ATS guidelines
- Treatment with a total daily dose of medium or high-dose ICS (e.g. ≥ 500μg fluticasone propionate, ≥ 800μg budesonide or equivalent total daily dose). ICS can be contained within an ICS/LABA combination product.
- At least one additional maintenance asthma controller e.g. LABA, LTRA, theophylline, LAMA, etc. with or without OCS
Who cannot join
- Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, urinalysis, vital signs, lung function at screening visit, which, in the opinion of the investigator, may either put the subject at risk because of participation in the study or may influence the results of the study, or the subject's ability to participate in the study.
- Past or present disease, which as judged by the investigator, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, hematological disease, neurological disease, endocrine disease or pulmonary disease other than Asthma (including but not confined to tuberculosis, bronchiectasis, cystic fibrosis, pulmonary hypertension, sarcoidosis, interstitial lung disease or lung fibrosis).
- History of drug or alcohol abuse.
- Risk of non-compliance with study procedures.
- Suspected inability to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study.
- History of an acute respiratory infection four weeks prior to enrolment. These patients will not be eligible, but will be permitted to be rescreened 4 weeks after the resolution of the respiratory tract infection.
Show all 11Show fewer
- Subjects with severe renal impairment (GFR ≤ 30 mL/min) including those with end-stage renal disease requiring dialysis or urinary retention.
- Subjects with active/ clinical history of COPD.
- Subjects unable to undergo MRI scans, including claustrophobia or presence of any metal objects within the patient, preventing from MRI scan (e.g. pacemaker, aneurysm clips).
- History of asthma exacerbation that required treatment with antibiotics, systemic steroids (oral or intravenous) or hospitalization within 3 months prior to enrolment.
- Subjects with a body mass index (BMI) of more than 35 kg/m2.
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
Hannover Medical School
Hanover, Lower Saxony, 30625
Jens Vogel-Claussen, MD, 00495115323421, vogel-claussen.jens@mh-hannover.de
Marius M Wernz, MSc, 004951153281248, wernz.marius@mh-hannover.de
About this study
Official title: FUNLUM: Functional Lung MRI for Early Treatment Response Assessment and Outcome Prediction for Patients With Severe Eosinophilic Asthma on Anti IL 5 Antibody Therapy
Patients with severe eosinophilic asthma will be placed on biologics if they continue to be uncontrolled despite maximized inhalation therapy or if they are only controlled under oral corticosteroids. Among biologics, 80% of patients respond to treatment and improve clinically, but approximately 20% are non-responders and up to date no established predictive factors for treatment response exist. Among the responders, about 30% respond very well (so-called super responders), the rest shows moderate improvements. As the lung function, one main criterion to evaluate treatment response improves in most patients with delay, the response (or non-response) to treatment can only be reliably estimated after 4 to 12 months. This can lead to prolonged use of medication in non-responders (overtreatment) on one hand and to unjustified and premature termination of therapy (undertreatment) on the other hand (GINA report 2019).
Functional lung MRI has the potential to show early changes in lung microstructure, regional ventilation and perfusion and thus has the potential for early detection of therapy response. Very promising results of dynamic regional ventilation and perfusion mapping using phase resolved functional lung (PREFUL) MRI have been shown recently.
However, if functional lung MRI can reliably detect treatment effects under Mepolizumab therapy and can help to predict a long-term patient outcome is still unknown. As these findings could directly influence clinical decision making this question is of high clinical relevance.
Read the detailed description
Asthma is a chronic disease and affects approximately 300 million people worldwide. Of these patients 3-10% have severe asthma which is defined as asthma remaining uncontrolled despite treatment with high-dose inhaled glucocorticoids combined with other controllers (long-acting β2-agonist, long-acting antimuscarinic agent, leukotriene receptor antagonist or theophylline) and/or treatment with systemic glucocorticoids for at least 6 months. Severe asthma causes a high amount of medical expenses in asthma. For patients suffering from severe uncontrolled asthma, an IL-5 antibody (mepolizumab) has been approved for therapy when a type 2 inflammation was present. Treatment is well tolerated and a significant reduction of exacerbations, oral glucocorticoid use was reported. Another IL-5 antibody (reslizumab) and an IL-5 receptor antibody (benralizumab) are available now.
Patients with severe eosinophilic asthma will be placed on biologics if they continue to be uncontrolled under maximal therapy or if they are only controlled under oral corticosteroids. Among biologics, 80% of patients improve, 20% are non-responders, but there is no way to identify them early. Among the responders, about 30% respond very well (so-called super responders), the rest shows moderate improvements. The main problems at the moment are that lung function improvements are only delayed, the response (or non-response) can only be reliably estimated after 4 to 12 months. This leads on the one hand to prolonged use of medication in non-responders (overtreatment), on the other hand to unjustified and premature termination of therapy (undertreatment) (GINA report 2019).
Study Rationale Functional lung MRI has the potential to show early changes in lung microstructure, regional ventilation and perfusion and thus has the potential for early detection of therapy response. Very promising results of dynamic regional ventilation and perfusion mapping using phase resolved functional lung (PREFUL) MRI have been shown recently. This technique holds the promise to mature into a patient friendly sensitive MRI spirometry test, with novel clinically relevant information to guide clinical decision making and improve patient monitoring. PREFUL MRI typically uses standard 1.5T or 3T MRI equipment and is based on a routine gradient echo fast low angle shot (FLASH) sequence. PREFUL is well suited also for children, because it is a free breathing exam without the need for i.v. contrast and has a relatively short examination time. The ventilation, perfusion and dynamic flow-volume loop maps are reconstructed entirely after the image acquisition using complex registration and post processing algorithms developed and validated at Hannover Medical School. Preliminary unpublished data show that PREFUL MRI may detect changes in regional ventilation 3 months after anti IL 5 antibody therapy treatment.
However, if functional lung MRI can reliably detect changes at 3 months of Mepolizumab treatment and can predict long term patient outcome is still unknown, which is of high clinical relevance for future clinical decision making.
The aim of this study is to examine if early treatment changes of Mepolizumab treatment can be detected at 3 months measured by functional lung MRI and predict clinical outcome at 12 months of treatment.
- Conditions
- Asthma; Eosinophilic
- Being tested
- Mepolizumab
- Medical subject headings
- Pulmonary Eosinophilia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MepolizumabDrug
Mepolizumab therapy
| Study group | Role | What they receive |
|---|---|---|
| eosinophilic asthma | Not described Receives: Drug: Mepolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Baseline ventilation-defect percentage by pulmonary MRI
Baseline airway function by measuring ventilation-defect percentage by pulmonary MRI.
Measured: baseline
Ventilation-defect percentage by pulmonary MRI after 3 months treatment with Mepolizumab
To study the effect of Mepolizumab treatment after 3 months treatment compared to baseline on airway function by measuring ventilation-defect percentage by pulmonary MRI.
Measured: 3 months
Baseline perfusion-defect percentage by pulmonary MRI
Baseline vascular function by measuring pulmonary perfusion-defect percentage by pulmonary MRI
Measured: baseline
Perfusion-defect percentage by pulmonary MRI after 3 months treatment with Mepolizumab
To study the effect of Mepolizumab treatment after 3 months treatment compared to baseline on vascular function by measuring pulmonary perfusion-defect percentage by pulmonary MRI
Measured: 3 months
Baseline ventilation/Perfusion mismatch by pulmonary MRI
Baseline Ventilation/Perfusion match and mismatch measured by pulmonary MRI.
Measured: baseline
Ventilation/Perfusion mismatch by pulmonary MRI after 3 months treatment with Mepolizumab
To study the effect of Mepolizumab treatment after 3 months treatment compared to baseline as Ventilation/Perfusion match and mismatch measured by pulmonary MRI.
Measured: 3 months
Secondary outcomes (15)
Ventilation-defect percentage by pulmonary MRI after 6 weeks treatment with Mepolizumab
To study the effect of Mepolizumab treatment after 6 weeks treatment compared to baseline on airway function by measuring ventilation-defect percentage by pulmonary MRI.
Measured: 6 weeks
Perfusion-defect percentage by pulmonary MRI after 6 weeks treatment with Mepolizumab
To study the effect of Mepolizumab treatment after 6 weeks treatment compared to baseline on airway function by measuring perfusion-defect percentage by pulmonary MRI.
Measured: 6 weeks
Ventilation/Perfusion mismatch by pulmonary MRI after 6 weeks treatment with Mepolizumab
To study the effect of Mepolizumab treatment after 6 weeks treatment compared to baseline on airway function by measuring ventilation/perfusion mismatch by pulmonary MRI.
Measured: 6 weeks
Baseline asthma control test
Baseline airway function measured by asthma control test (ACT)
Measured: baseline
Asthma control test after 12 months of treatment with Mepolizumab
To study the effect of Mepolizumab treatment after 12 months compared to baseline on airway function measured by asthma control test (ACT).
Measured: 12 months
Baseline Clinical lung function
Baseline airway function measured by Clinical lung function via bodyplesmography
Measured: baseline
Clinical lung function after 12 months of treatment with Mepolizumab
To study the effect of Mepolizumab treatment after 12 months compared to baseline on airway function measured by Clinical lung function via bodyplesmography
Measured: 12 months
Baseline fractional exhaled nitric oxide
Baseline airway function measured by fractional exhaled nitrix oxide (FeNO)
Measured: baseline
Fractional exhaled nitric oxide after 12 months of treatment with Mepolizumab
To study the effect of Mepolizumab treatment after 12 months compared to baseline on airway function measured by fractional exhaled nitrix oxide (FeNO)
Measured: 12 months
Baseline capillary blood gas analysis
Baseline airway function measured by capillary blood gas analysis
Measured: baseline
Capillary blood gas analysis after 12 months of treatment with Mepolizumab
To study the effect of Mepolizumab treatment after 12 months compared to baseline on airway function measured by capillary blood gas analysis
Measured: 12 months
Baseline blood eosinophil cell count
Baseline airway function measured by blood eosinophil cell count
Measured: baseline
Blood eosinophil cell count after 12 months of treatment with Mepolizumab
To study the effect of Mepolizumab treatment after 12 months compared to baseline on airway function measured by blood eosinophil cell count
Measured: 12 months
Baseline exacerbation rate
Baseline airway function measured by exacerbation rate
Measured: baseline
Exacerbation rate after 12 months of treatment with Mepolizumab
To study the effect of Mepolizumab treatment after 12 months compared to baseline on airway function measured by exacerbation rate
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2020
- Study start4 May 2020
- Primary completionFeb 2025 (estimated)
- Study completionAug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for Asthma; EosinophilicStudies of the same condition, open and under way.
- 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
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hannover Medical School
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Jens Vogel-Claussen, MD, Principal investigator, Hannover Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04512521
- Sponsor's protocol ID
- 8832_BO_S_2020
- Other IDs
- 213598
- Acronym
- FUNLUM
- Status last verified
- Mar 2023
- First submitted
- 29 Jul 2020
- Last updated
- 10 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
To T, Stanojevic S, Moores G, Gershon AS, Bateman ED, Cruz AA, Boulet LP. Global asthma prevalence in adults: findings from the cross-sectional world health survey. BMC Public Health. 2012 Mar 19;12:204. doi: 10.1186/1471-2458-12-204.
PubMed 22429515Hekking PW, Wener RR, Amelink M, Zwinderman AH, Bouvy ML, Bel EH. The prevalence of severe refractory asthma. J Allergy Clin Immunol. 2015 Apr;135(4):896-902. doi: 10.1016/j.jaci.2014.08.042. Epub 2014 Oct 16.
PubMed 25441637Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, Adcock IM, Bateman ED, Bel EH, Bleecker ER, Boulet LP, Brightling C, Chanez P, Dahlen SE, Djukanovic R, Frey U, Gaga M, Gibson P, Hamid Q, Jajour NN, Mauad T, Sorkness RL, Teague WG. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014 Feb;43(2):343-73. doi: 10.1183/09031936.00202013. Epub 2013 Dec 12.
PubMed 24337046Braman SS. The global burden of asthma. Chest. 2006 Jul;130(1 Suppl):4S-12S. doi: 10.1378/chest.130.1_suppl.4S.
PubMed 16840363Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, Ortega H, Chanez P. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012 Aug 18;380(9842):651-9. doi: 10.1016/S0140-6736(12)60988-X.
PubMed 22901886Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2015 Apr 30;372(18):1777. doi: 10.1056/NEJMx150017. Epub 2015 Apr 10. No abstract available.
PubMed 25860645Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, Ortega HG, Pavord ID; SIRIUS Investigators. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014 Sep 25;371(13):1189-97. doi: 10.1056/NEJMoa1403291. Epub 2014 Sep 8.
PubMed 25199060Castro M, Zangrilli J, Wechsler ME, Bateman ED, Brusselle GG, Bardin P, Murphy K, Maspero JF, O'Brien C, Korn S. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med. 2015 May;3(5):355-66. doi: 10.1016/S2213-2600(15)00042-9. Epub 2015 Feb 23.
PubMed 25736990Nair P, Wenzel S, Rabe KF, Bourdin A, Lugogo NL, Kuna P, Barker P, Sproule S, Ponnarambil S, Goldman M; ZONDA Trial Investigators. Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma. N Engl J Med. 2017 Jun 22;376(25):2448-2458. doi: 10.1056/NEJMoa1703501. Epub 2017 May 22.
PubMed 28530840Voskrebenzev A, Gutberlet M, Klimes F, Kaireit TF, Schonfeld C, Rotarmel A, Wacker F, Vogel-Claussen J. Feasibility of quantitative regional ventilation and perfusion mapping with phase-resolved functional lung (PREFUL) MRI in healthy volunteers and COPD, CTEPH, and CF patients. Magn Reson Med. 2018 Apr;79(4):2306-2314. doi: 10.1002/mrm.26893. Epub 2017 Aug 30.
PubMed 28856715Kaireit TF, Gutberlet M, Voskrebenzev A, Freise J, Welte T, Hohlfeld JM, Wacker F, Vogel-Claussen J. Comparison of quantitative regional ventilation-weighted fourier decomposition MRI with dynamic fluorinated gas washout MRI and lung function testing in COPD patients. J Magn Reson Imaging. 2018 Jun;47(6):1534-1541. doi: 10.1002/jmri.25902. Epub 2017 Nov 21.
PubMed 29160020Kaireit TF, Voskrebenzev A, Gutberlet M, Freise J, Jobst B, Kauczor HU, Welte T, Wacker F, Vogel-Claussen J. Comparison of quantitative regional perfusion-weighted phase resolved functional lung (PREFUL) MRI with dynamic gadolinium-enhanced regional pulmonary perfusion MRI in COPD patients. J Magn Reson Imaging. 2019 Apr;49(4):1122-1132. doi: 10.1002/jmri.26342. Epub 2018 Oct 22.
PubMed 30350440Klimes F, Voskrebenzev A, Gutberlet M, Kern A, Behrendt L, Kaireit TF, Czerner C, Renne J, Wacker F, Vogel-Claussen J. Free-breathing quantification of regional ventilation derived by phase-resolved functional lung (PREFUL) MRI. NMR Biomed. 2019 Jun;32(6):e4088. doi: 10.1002/nbm.4088. Epub 2019 Mar 25.
PubMed 30908743Bauman G, Puderbach M, Deimling M, Jellus V, Chefd'hotel C, Dinkel J, Hintze C, Kauczor HU, Schad LR. Non-contrast-enhanced perfusion and ventilation assessment of the human lung by means of fourier decomposition in proton MRI. Magn Reson Med. 2009 Sep;62(3):656-64. doi: 10.1002/mrm.22031.
PubMed 19585597Moher Alsady T, Voskrebenzev A, Greer M, Becker L, Kaireit TF, Welte T, Wacker F, Gottlieb J, Vogel-Claussen J. MRI-derived regional flow-volume loop parameters detect early-stage chronic lung allograft dysfunction. J Magn Reson Imaging. 2019 Dec;50(6):1873-1882. doi: 10.1002/jmri.26799. Epub 2019 May 27.
PubMed 31134705
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- FUNLUM: Functional Lung MRI for Early Treatment Response Assessment and Outcome Prediction for Patients With Severe Eosinophilic Asthma on Anti IL 5 Antibody Therapy
- ClinicalTrials.gov ID
- NCT04512521
- Acronym / sponsor ID
- FUNLUM / 8832_BO_S_2020
- Conditions
- Asthma; Eosinophilic
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Hannover Medical SchoolUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- 4 May 2020 (actual)
- Primary completion
- Feb 2025 (estimated)
- Study completion
- Aug 2025 (estimated)
- First posted
- 13 Aug 2020 (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.
Patients with severe eosinophilic asthma will be placed on biologics if they continue to be uncontrolled despite maximized inhalation therapy or if they are only controlled under oral corticosteroids. Among biologics, 80% of patients respond to treatment and improve clinically, but approximately 20% are non-responders and up to date no established predictive factors for treatment response exist. Among the responders, about 30% respond very well (so-called super responders), the rest shows moderate improvements. As the lung function, one main criterion to evaluate treatment response improves in most patients with delay, the response (or non-response) to treatment can only be reliably estimated after 4 to 12 months. This can lead to prolonged use of medication in non-responders (overtreatment) on one hand and to unjustified and premature termination of therapy (undertreatment) on the other hand (GINA report 2019).
Functional lung MRI has the potential to show early changes in lung microstructure, regional ventilation and perfusion and thus has the potential for early detection of therapy response. Very promising results of dynamic regional ventilation and perfusion mapping using phase resolved functional lung (PREFUL) MRI have been shown recently.
However, if functional lung MRI can reliably detect treatment effects under Mepolizumab therapy and can help to predict a long-term patient outcome is still unknown. As these findings could directly influence clinical decision making this question is of high clinical relevance.
Detailed description
Asthma is a chronic disease and affects approximately 300 million people worldwide. Of these patients 3-10% have severe asthma which is defined as asthma remaining uncontrolled despite treatment with high-dose inhaled glucocorticoids combined with other controllers (long-acting β2-agonist, long-acting antimuscarinic agent, leukotriene receptor antagonist or theophylline) and/or treatment with systemic glucocorticoids for at least 6 months. Severe asthma causes a high amount of medical expenses in asthma. For patients suffering from severe uncontrolled asthma, an IL-5 antibody (mepolizumab) has been approved for therapy when a type 2 inflammation was present. Treatment is well tolerated and a significant reduction of exacerbations, oral glucocorticoid use was reported. Another IL-5 antibody (reslizumab) and an IL-5 receptor antibody (benralizumab) are available now.
Patients with severe eosinophilic asthma will be placed on biologics if they continue to be uncontrolled under maximal therapy or if they are only controlled under oral corticosteroids. Among biologics, 80% of patients improve, 20% are non-responders, but there is no way to identify them early. Among the responders, about 30% respond very well (so-called super responders), the rest shows moderate improvements. The main problems at the moment are that lung function improvements are only delayed, the response (or non-response) can only be reliably estimated after 4 to 12 months. This leads on the one hand to prolonged use of medication in non-responders (overtreatment), on the other hand to unjustified and premature termination of therapy (undertreatment) (GINA report 2019).
Study Rationale Functional lung MRI has the potential to show early changes in lung microstructure, regional ventilation and perfusion and thus has the potential for early detection of therapy response. Very promising results of dynamic regional ventilation and perfusion mapping using phase resolved functional lung (PREFUL) MRI have been shown recently. This technique holds the promise to mature into a patient friendly sensitive MRI spirometry test, with novel clinically relevant information to guide clinical decision making and improve patient monitoring. PREFUL MRI typically uses standard 1.5T or 3T MRI equipment and is based on a routine gradient echo fast low angle shot (FLASH) sequence. PREFUL is well suited also for children, because it is a free breathing exam without the need for i.v. contrast and has a relatively short examination time. The ventilation, perfusion and dynamic flow-volume loop maps are reconstructed entirely after the image acquisition using complex registration and post processing algorithms developed and validated at Hannover Medical School. Preliminary unpublished data show that PREFUL MRI may detect changes in regional ventilation 3 months after anti IL 5 antibody therapy treatment.
However, if functional lung MRI can reliably detect changes at 3 months of Mepolizumab treatment and can predict long term patient outcome is still unknown, which is of high clinical relevance for future clinical decision making.
The aim of this study is to examine if early treatment changes of Mepolizumab treatment can be detected at 3 months measured by functional lung MRI and predict clinical outcome at 12 months of treatment.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| eosinophilic asthma | – | Drug: Mepolizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The patients will be selected for this study consecutively by Dr. Suhling (or colleagues; Dr. Drick) from his Asthma outpatient clinic according to his clinical judgement.
Key inclusion criteria (6 listed)
- Able and willing to give written informed consent.
- Male and female subjects, aged ≥ 18 years.
- Patients which are eligible for treatment using anti-IL-5 -antibody treatment following guidelines: severe eosinophilic asthma and blood eosinophils of ≥150 cells/μL at screening or ≥ 300 cells/μL within 12 months prior to treatment
- Physician-diagnosed severe asthma according to ERS/ATS guidelines
- Treatment with a total daily dose of medium or high-dose ICS (e.g. ≥ 500μg fluticasone propionate, ≥ 800μg budesonide or equivalent total daily dose). ICS can be contained within an ICS/LABA combination product.
Key exclusion criteria (11 listed)
- Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, urinalysis, vital signs, lung function at screening visit, which, in the opinion of the investigator, may either put the subject at risk because of participation in the study or may influence the results of the study, or the subject's ability to participate in the study.
- Past or present disease, which as judged by the investigator, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, hematological disease, neurological disease, endocrine disease or pulmonary disease other than Asthma (including but not confined to tuberculosis, bronchiectasis, cystic fibrosis, pulmonary hypertension, sarcoidosis, interstitial lung disease or lung fibrosis).
- History of drug or alcohol abuse.
- Risk of non-compliance with study procedures.
- Suspected inability to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study.
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 |
|---|---|---|
| MepolizumabMepolizumab therapy | Drug | eosinophilic asthma |
Primary outcome
Baseline ventilation-defect percentage by pulmonary MRI
Time frame: baseline
Baseline airway function by measuring ventilation-defect percentage by pulmonary MRI.
Ventilation-defect percentage by pulmonary MRI after 3 months treatment with Mepolizumab
Time frame: 3 months
To study the effect of Mepolizumab treatment after 3 months treatment compared to baseline on airway function by measuring ventilation-defect percentage by pulmonary MRI.
Baseline perfusion-defect percentage by pulmonary MRI
Time frame: baseline
Baseline vascular function by measuring pulmonary perfusion-defect percentage by pulmonary MRI
Perfusion-defect percentage by pulmonary MRI after 3 months treatment with Mepolizumab
Time frame: 3 months
To study the effect of Mepolizumab treatment after 3 months treatment compared to baseline on vascular function by measuring pulmonary perfusion-defect percentage by pulmonary MRI
Baseline ventilation/Perfusion mismatch by pulmonary MRI
Time frame: baseline
Baseline Ventilation/Perfusion match and mismatch measured by pulmonary MRI.
Ventilation/Perfusion mismatch by pulmonary MRI after 3 months treatment with Mepolizumab
Time frame: 3 months
To study the effect of Mepolizumab treatment after 3 months treatment compared to baseline as Ventilation/Perfusion match and mismatch measured by pulmonary MRI.
15 secondary outcomes
Ventilation-defect percentage by pulmonary MRI after 6 weeks treatment with Mepolizumab
Time frame: 6 weeks
Perfusion-defect percentage by pulmonary MRI after 6 weeks treatment with Mepolizumab
Time frame: 6 weeks
Ventilation/Perfusion mismatch by pulmonary MRI after 6 weeks treatment with Mepolizumab
Time frame: 6 weeks
Baseline asthma control test
Time frame: baseline
Asthma control test after 12 months of treatment with Mepolizumab
Time frame: 12 months
Baseline Clinical lung function
Time frame: baseline
Clinical lung function after 12 months of treatment with Mepolizumab
Time frame: 12 months
Baseline fractional exhaled nitric oxide
Time frame: baseline
Fractional exhaled nitric oxide after 12 months of treatment with Mepolizumab
Time frame: 12 months
Baseline capillary blood gas analysis
Time frame: baseline
Capillary blood gas analysis after 12 months of treatment with Mepolizumab
Time frame: 12 months
Baseline blood eosinophil cell count
Time frame: baseline
Blood eosinophil cell count after 12 months of treatment with Mepolizumab
Time frame: 12 months
Baseline exacerbation rate
Time frame: baseline
Exacerbation rate after 12 months of treatment with Mepolizumab
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2023.
- Background: PubMed 22429515To T, Stanojevic S, Moores G, Gershon AS, Bateman ED, Cruz AA, Boulet LP. Global asthma prevalence in adults: findings from the cross-sectional world health survey. BMC Public Health. 2012 Mar 19;12:204. doi: 10.1186/1471-2458-12-204.
- Background: PubMed 25441637Hekking PW, Wener RR, Amelink M, Zwinderman AH, Bouvy ML, Bel EH. The prevalence of severe refractory asthma. J Allergy Clin Immunol. 2015 Apr;135(4):896-902. doi: 10.1016/j.jaci.2014.08.042. Epub 2014 Oct 16.
- Background: PubMed 24337046Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, Adcock IM, Bateman ED, Bel EH, Bleecker ER, Boulet LP, Brightling C, Chanez P, Dahlen SE, Djukanovic R, Frey U, Gaga M, Gibson P, Hamid Q, Jajour NN, Mauad T, Sorkness RL, Teague WG. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014 Feb;43(2):343-73. doi: 10.1183/09031936.00202013. Epub 2013 Dec 12.
- Background: PubMed 16840363Braman SS. The global burden of asthma. Chest. 2006 Jul;130(1 Suppl):4S-12S. doi: 10.1378/chest.130.1_suppl.4S.
- Background: PubMed 22901886Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, Ortega H, Chanez P. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012 Aug 18;380(9842):651-9. doi: 10.1016/S0140-6736(12)60988-X.
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- Background: PubMed 25736990Castro M, Zangrilli J, Wechsler ME, Bateman ED, Brusselle GG, Bardin P, Murphy K, Maspero JF, O'Brien C, Korn S. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med. 2015 May;3(5):355-66. doi: 10.1016/S2213-2600(15)00042-9. Epub 2015 Feb 23.
- Background: PubMed 28530840Nair P, Wenzel S, Rabe KF, Bourdin A, Lugogo NL, Kuna P, Barker P, Sproule S, Ponnarambil S, Goldman M; ZONDA Trial Investigators. Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma. N Engl J Med. 2017 Jun 22;376(25):2448-2458. doi: 10.1056/NEJMoa1703501. Epub 2017 May 22.
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- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Jens Vogel-Claussen, MD principal investigator
Hannover Medical School
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 Asthma; Eosinophilic, run by Hannover Medical School at 1 site in Germany.
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 6 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 10 Mar 2023. 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 Germany. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hendrik Suhling, MD (00495115323230, Suhling.Hendrik@mh-hannover.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Baseline ventilation-defect percentage by pulmonary MRI (time frame: baseline). The study lists 6 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 NCT04512521, which also lists 25 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 10 Mar 2023.