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Inflammation Following Mepolizumab and Oral Corticosteroids in Asthma (MAPLE)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03610685
Recruitment Status : Completed
First Posted : August 1, 2018
Last Update Posted : March 6, 2020
Sponsor:
Collaborator:
Queen's University, Belfast
Information provided by (Responsible Party):
NHS Greater Glasgow and Clyde

Brief Summary:
The aim of the project is to study the persistence of inflammation after addition of an interleukin-5 (IL-5) blocker in severe eosinophilic asthma as a study of untreated pathways in these patients.

Condition or disease Intervention/treatment Phase
Asthma Drug: Prednisolone Drug: Placebo oral capsule Phase 4

Detailed Description:

Mepolizumab, a humanized monoclonal antibody (mAb) antagonizes IL-5 and through a selective inhibition of eosinophilic inflammation, reduces the number of eosinophils in sputum and blood, leading to a reduction in asthma exacerbations and a need for systemic glucocorticoids. Once this therapy has been initiated for severe eosinophilic asthma, the additional role of oral corticosteroids is questionable as their main target is reduction of eosinophils and hence responsiveness to oral corticosteroids in patients in a stable state of asthma may reduce.

Using two weeks of high dose prednisolone versus placebo in a crossover design after 12 weeks of mepolizumab therapy will allow an understanding of the pathways that remain steroid responsive following IL-5 suppression.

This is an exploratory study with no single primary end point. The objective of the study is to assess the change in airway inflammation following oral corticosteroids versus placebo and the airway inflammation while on mepolizumab in stable state of asthma.

Note: Mepolizumab is not an intervention in this study; it is initiated as part of usual NHS care.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 33 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: Persistence of Inflammation and Study of T2 Pathways Following Inhibition of InterLeukin-5 With Mepolizumab in Severe Eosinophilic Asthma
Actual Study Start Date : October 19, 2018
Actual Primary Completion Date : January 7, 2020
Actual Study Completion Date : January 7, 2020


Arm Intervention/treatment
Placebo Comparator: Placebo
Participants will be given 2 weeks of placebo treatment. The placebo capsules will be taken once a day orally. The daily dose of placebo treatment will match the Prednisone dose for each participant.
Drug: Placebo oral capsule
Given daily for 2 weeks
Other Name: Placebo

Active Comparator: Prednisolone
Participants will be given 2 weeks of prednisolone treatment. This is administered orally once a day. The daily dose is calculated according to 0.5mg/kg with a maximum dose of 40mg per day.
Drug: Prednisolone
Given daily for 2 weeks




Primary Outcome Measures :
  1. Change in exhaled nitric oxide measured in parts per billion [ Time Frame: Through study completion, an average 20 weeks. ]
    Measured at study visits using a Niox machine.

  2. Change in sputum differential cell counts measured in absolute cell count. [ Time Frame: Through study completion, an average 20 weeks ]
    Induced sputum


Other Outcome Measures:
  1. Change in asthma control and quality of life questionnaires [ Time Frame: Through study completion, an average 20 weeks. ]

    Asthma control questionnaire includes 5 questions related to asthma control. Each question is scored from 0 to 6 with the highest number representing poorer outcome / asthma control.

    Asthma quality of life questionnaire includes 32 questions related to quality of life. Each question is scored from 1 to 7 with the highest number representing better outcome / quality of life.


  2. Change in visual asthma symptom scores [ Time Frame: Through study completion, an average 20 weeks ]
    Symptoms visual analogue scale asks 3 questions related to asthma control. A

  3. Oscillometry [ Time Frame: Through study completion, an average 20 weeks ]
    For small airway function to correlate with inflammation



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age ≥ 18 and ≤ 80 years at consent.
  • Able and willing to provide written informed consent and to comply with the study protocol.
  • Severe asthma diagnosis confirmed after assessment by an asthma specialist.
  • Suitable for mepolizumab as per NICE/SMC Clinical Guidelines.

Exclusion Criteria:

  • Maintenance oral corticosteroid treatment within the past four weeks.
  • Acute exacerbation requiring oral corticosteroids in the four weeks prior to consent.
  • Other clinically significant medical disease or uncontrolled concomitant disease despite treatment that is likely, in the opinion of the investigator, to require a change in therapy or impact the ability to participate in the study or be significantly worsened by oral corticosteroids.
  • History of current alcohol, drug, or chemical abuse or past abuse that would impair or risk the subject's full participation in the study, in the opinion of the investigator.
  • Treatment with an investigational agent within 30 days of Visit 1 (or five half-lives of the investigational agent, whichever is longer).
  • Women of child-bearing potential who are pregnant, lactating, planning pregnancy during the study period or are unwilling to use a highly effective form of contraception.
  • Known hypersensitivity to prednisolone or its excipients.
  • Previous psychiatric adverse reactions to steroid therapy in the past.
  • Concomitant medication with systemic anti-fungals such as ketoconazole, retinoids, tetracycline, other systemic immunosuppressants e.g. ciclosporin, azathioprine, mycophenolate and live vaccines during the crossover trial.

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): NCT03610685


Locations
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United Kingdom
Asthma and copd research centre
Glasgow, United Kingdom, G12 0YN
Sponsors and Collaborators
NHS Greater Glasgow and Clyde
Queen's University, Belfast
Investigators
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Principal Investigator: Rekha Chaudhuri, MD NHS Greater Glasgow and Clyde

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Responsible Party: NHS Greater Glasgow and Clyde
ClinicalTrials.gov Identifier: NCT03610685    
Other Study ID Numbers: GN17RM707
First Posted: August 1, 2018    Key Record Dates
Last Update Posted: March 6, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by NHS Greater Glasgow and Clyde:
Severe asthma
Mepolizumab
IL5
Steroid resistance
Eosinophilic asthma
Type 2 inflammation
Additional relevant MeSH terms:
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Asthma
Inflammation
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Pathologic Processes
Prednisolone
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents