Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Pilot Study of the Use of 129Xe and 1H MRI to Measure the Modulation of Eosinophil-Related Inflammation by Mepolizumab In COPD (SUMMER)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05138250
Recruitment Status : Not yet recruiting
First Posted : November 30, 2021
Last Update Posted : November 30, 2021
Sponsor:
Collaborator:
University of Sheffield
Information provided by (Responsible Party):
Sheffield Teaching Hospitals NHS Foundation Trust

Brief Summary:
The investigators aim to recruit 32 people with COPD who have frequent exacerbations and high eosinophil counts which indicates "asthmatic type" inflammation and treat them for a year with mepolizumab. This is a licenced medication for asthma. Mepolizumab is a monoclonal antibody that acts through interleukin-5 (IL-5) antagonism to reduce blood eosinophil levels and is effective at reducing exacerbations in asthmatics. To determine whether mepolizumab may be an effective treatment in people with COPD and "asthmatic type" inflammation participants will have MRI scans before the treatment, after 12 weeks and after a year to see how the drug affects inflammation. The investigators will also compare our measurements with the number of exacerbations people get (measured by diaries), with measures of their quality of life (using a questionnaire), and with ordinary laboratory breathing tests. The investigators are especially interested to know if the reduction in inflammation early on after 12 weeks is associated with fewer exacerbations and better quality of life over the year.

Condition or disease Intervention/treatment Phase
COPD Drug: Mepolizumab 100 MG Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of the Use of 129Xe and 1H MRI to Measure the Modulation of Eosinophil-Related Inflammation by Mepolizumab In COPD
Estimated Study Start Date : April 2022
Estimated Primary Completion Date : June 2024
Estimated Study Completion Date : September 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Mepolizumab

Arm Intervention/treatment
Experimental: Treatment arm (all participants, not randomised)
All participants will be treated with mepolizumab, a 100mg dose every 4 weeks for 1 year (13 doses)
Drug: Mepolizumab 100 MG
participants will receive 100mg of mepolizumab every 4 weeks for 52 weeks




Primary Outcome Measures :
  1. Change in percentage ventilated volume of lung (%VV) [ Time Frame: 12 weeks ]
    The within subject change in percentage ventilated volume of lung (%VV) assessed by XeMRI from baseline to 12 weeks of treatment with mepolizumab

  2. Change in alveolar thickness [ Time Frame: 12 weeks ]
    The within participant change in TP/gas (a measure of alveolar thickness, as an index of pulmonary inflammation) assessed by XeMRI from baseline to 12 weeks of treatment with mepolizumab.


Secondary Outcome Measures :
  1. Change in MRI metrics in low and high exacerbation groups [ Time Frame: 12 weeks ]
    Comparison of change in MRI metrics from baseline to 12 weeks in groups with a) low or b) high total 52 week exacerbation (groups defined by median split of total exacerbations over 52 weeks assessed by EXACT-Pro)

  2. Change in MRI indices of ventilation, perfusion and inflammation - 12 weeks [ Time Frame: 12 weeks ]
    Change in MRI indices of ventilation, perfusion and inflammation - CV, RBC/TP, RBC/gas, ADC, LmD, Ve, Ktrans, PBV, PBF, MTT, VQ-intersect, T1, M0 from baseline to 12 weeks


Other Outcome Measures:
  1. Change in MRI indices of ventilation, perfusion and inflammation - 52 weeks [ Time Frame: 52 weeks ]
    Change in MRI indices of ventilation, perfusion and inflammation (see text) - %VV, CV, RBC/TP, TP/gas, RBC/gas, ADC, LmD, Ve, Ktrans, PBV, PBF, MTT, VQ-intersect, T1, M0 at 52 weeks compared to baseline and 12 weeks

  2. Correlation of changes to measures of lung function and inflammation (MRI and physiological) [ Time Frame: 12 weeks ]
    Correlation of changes in physiological measures and MRI measures of lung function and inflammation (see text) at 12 weeks

  3. Various correlations of change of ventilation, perfusion and inflammation measures [ Time Frame: 12 weeks and 52 weeks ]

    Change in physiological and MRI determined measures of ventilation, perfusion and inflammation at 12 weeks from baseline will be correlated with;

    1. Baseline peripheral blood eosinophil count
    2. Baseline FeNO
    3. Change of peripheral blood eosinophil count from baseline to 12 weeks
    4. Change in FeNO from baseline to 12 weeks. Similar correlation will be carried out for data obtained at 52 weeks rather than 12 weeks.

  4. Change in MRI metrics in groups with low or high numbers of moderate to severe exacerbations [ Time Frame: 12 weeks ]
    Comparison of change in MRI metrics from baseline to 12 weeks in groups with a) low or b) high total 52 week exacerbation (groups defined by median split of total moderate to severe exacerbations over 52 weeks assessed by EXACT-Pro)

  5. Overall impact of mepolizumab treatment on HRQoL in COPD [ Time Frame: 12 and 52 weeks ]
    Comparison of change of CAT from baseline to 12 and 52 weeks within participants compare to changes in measures of lung function by physiology and MRI.

  6. Overall impact of mepolizumab treatment on HRQoL in COPD [ Time Frame: 12 and 52 weeks ]
    Comparison of changes in physiological and MRI derived parameters at 12 weeks in groups with either high and low improvement of CAT at 52 weeks (determined by median split)

  7. Correlation of PREFUL and DCE MRI measures [ Time Frame: 52 weeks (all timepoints) ]
    PREFUL %VV and PREFUL %PV will be correlated with XeMRI and proton MRI determined measures of lung function at all time points



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of COPD as determined by a post bronchodilator FEV1/FVC <70% and an FEV1 of between 20 and 80% at screening visit
  • Treatment with inhaled triple therapy (licensed combination of long acting beta 2 agonist, long acting anti-muscarinic and corticosteroid) at constant dose for at least 12 weeks before screening visit. Treatment with roflumilast, theophyillines and macrolides will be permitted so long as they were introduced at stable dose > 12 weeks prior to screening visit. (If maintenance drug dosing has not been with stable dosages for 12 weeks the screening visit may be rescheduled until this is achieved: see sections 7.3 and 7.10)
  • At least 2 acute exacerbations of COPD (AECOPD) requiring treatment with oral steroids and/or antibiotics in the last 12 months, or 1 acute AECOPD requiring hospital admission in the last 12 months.
  • At least one eosinophil count of >0.3 cells·μL-1 in the 12 months prior to screening
  • Age over 18 years

Exclusion Criteria:

  • Contraindication to MRI scanning, including Gadovist (ie hypersensitivity or poor renal function; see below); this includes claustrophobia and musculoskeletal difficulties, this information is collected on the UoS MRI unit screening form.
  • Inability to give informed consent or comply with study procedures
  • Hypersensitivity to mepolizumab or its excipients
  • Untreated helminthic infection
  • Exacerbation of COPD requiring treatment with oral steroids and/or antibiotics within 4 weeks of screening. A repeat screening visit may be scheduled in order to achieve this criterion. The participant will be required to successfully complete all screening procedures at the rescheduled visit, including that for exacerbation-free stability.
  • SpO2 <90% on room air at screening
  • Clear history of childhood and/or current asthma
  • Past history of lung surgery
  • Other significant lung disease
  • Long term oral steroid treatment
  • eGFR < 30 ml/min/1.73 m2 at screening
  • NYHA class 3 or 4, where the functional limitation from heart disease is greater than that from COPD, or uncompensated heart failure
  • Chronic liver disease (Any elevation of ALT above twice the upper limit of normal at screening. Lower levels of abnormality are permitted after investigator review if felt not to compromise safety)
  • Malignancy unless treated and disease free for 5 years
  • Conditions causing significant immunosuppression
  • Active infection with blood borne viruses (including hepatitis A and B and HIV)
  • Other significant medical condition compromising participant safety or fidelity of study.
  • Pregnant or breast feeding
  • Of childbearing potential and not willing to use highly effective methods of contraception during the course of the study and for 100 days post last dose of mepolizumab.
  • Participants who have received an investigational drug within 30 days of first dose, or within 5 drug half-lives of the investigational drug, whichever is longer

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05138250


Contacts
Layout table for location contacts
Contact: Rod Lawson 01142714278 rod.lawson@nhs.net
Contact: Lisa Watson 01142265424 lisa.watson24@nhs.net

Sponsors and Collaborators
Sheffield Teaching Hospitals NHS Foundation Trust
University of Sheffield
Investigators
Layout table for investigator information
Principal Investigator: Rod Lawson Sheffield Teaching Hospitals NHS Foundation Trust
Layout table for additonal information
Responsible Party: Sheffield Teaching Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT05138250    
Other Study ID Numbers: STH21067
First Posted: November 30, 2021    Key Record Dates
Last Update Posted: November 30, 2021
Last Verified: November 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Sheffield Teaching Hospitals NHS Foundation Trust:
MRI, eosinophil, exacerbation
Additional relevant MeSH terms:
Layout table for MeSH terms
Inflammation
Pathologic Processes