Functional Lung MRI for Early Treatment Response Assessment for Patients With Eosinophilic Asthma

NCT04512521 | Unknown

• 2 other identifiers: 8832_BO_S_2020213598
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Asthma; Eosinophilic

Outcome Measures

Primary Outcomes (6)

• Baseline ventilation-defect percentage by pulmonary MRI

  Baseline airway function by measuring ventilation-defect percentage by pulmonary MRI.

  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.

  3 months

• Baseline perfusion-defect percentage by pulmonary MRI

  Baseline vascular function by measuring pulmonary perfusion-defect percentage by pulmonary MRI

  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

  3 months

• Baseline ventilation/Perfusion mismatch by pulmonary MRI

  Baseline Ventilation/Perfusion match and mismatch measured by pulmonary MRI.

  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.

  3 months

Secondary Outcomes (15)

• Ventilation-defect percentage by pulmonary MRI after 6 weeks treatment with Mepolizumab

  6 weeks

• Perfusion-defect percentage by pulmonary MRI after 6 weeks treatment with Mepolizumab

  6 weeks

• Ventilation/Perfusion mismatch by pulmonary MRI after 6 weeks treatment with Mepolizumab

  6 weeks

• Baseline asthma control test

  baseline

• Asthma control test after 12 months of treatment with Mepolizumab

  12 months

Study Arms (1)

eosinophilic asthma

Drug: Mepolizumab

Interventions

Mepolizumab DRUG

Mepolizumab therapy

eosinophilic asthma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Hannover Medical School: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Hannover Medical School

Hanover, Lower Saxony, 30625, Germany

RECRUITING

Related Publications (25)

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• Kaireit 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.

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• Klimes 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.

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Biospecimen

Retention: SAMPLES WITHOUT DNA

blood eosinophil cell count, IgE FENO capillary BGA

MeSH Terms

Conditions

Pulmonary Eosinophilia

Interventions

mepolizumab

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypereosinophilic Syndrome; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Jens Vogel-Claussen, MD

  Hannover Medical School

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hendrik Suhling, MD

CONTACT

00495115323230; Suhling.Hendrik@mh-hannover.de

Marius M Wernz, MSc

CONTACT

004951153281248; wernz.marius@mh-hannover.de

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2020
• First Posted: August 13, 2020
• Study Start: May 4, 2020
• Primary Completion: February 1, 2025
• Study Completion: August 1, 2025
• Last Updated: March 10, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)