eGPA and Local Inflammation Within the Ear, Nose and Throat Area

Impact of Mepolizumab Treatment on the Nasal Microbiome and Local and Systemic Immune Response in Eosinophilic Granulomatosis With Polyangitis (eGPA)

Rationale: Eosinophilic Granulomatosis with Polyangiitis (eGPA), eosinophilic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) are airway diseases where eosinophils and interleukine-5 are involved in the pathogenesis. eGPA differs from the other diseases with respect to involvement of other organs. The investigators hypothesize that nasal microbiome dysbiosis with a central augmenting role for S. Aureus plays an important role in disease expression. The investigators expect that anti-interleukin-5 treatment with mepolizumab restores the changes of the nasal microbiome and immune responses to a healthy control phenotype. To study this, the nasal microbiome, the local and systemic immune response and the effect of mepolizumab treatment will be assessed.

Study Overview

• Status: Recruiting
• Conditions: EGPA - Eosinophilic Granulomatosis With Polyangiitis
• Intervention / Treatment: Diagnostic test: laboratory experiments before and after mepolizumab treatment

Detailed Description

See Brief summary.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Abraham Rutgers, MD-PhD; Phone Number: +31503616161; Email: a.rutgers@umcg.nl

Study Locations

• Netherlands
  • Groningen, Netherlands, 9700RB
    • Recruiting
    • UMC Groningen
    • Contact: Abraham Rutgers, MD-PhD; Phone Number: +31503616161; Email: a.rutgers@umcg.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with eosinophil driven inflammation for which mepolizumab might be considered for treatment

Description

Inclusion Criteria:

• 18 years of age

  • able to give informed consent
  • In CRSwNP group: availability of bilateral nasal polyps as diagnosed by endoscopy or CT scan
  • In Severe asthma group: clinical diagnosis of asthma with forced expiratory volume at one second(FEV1) <80% AND either FEV1 reversibility >12% initial or documented positive metacholine challenge (PC20 < 8 mg/ml)
  • In eGPA group: Fulfilling the 2022 ACR/EULAR criteria for eGPA (Wechsler et al., 2017)
  • In GPA group: fulfilling the American College of Rheumatology (ACR)/EULAR GPA criteria (Robson et al., 2022)
  • In healthy controls: absence of asthma symptoms, no bronchial hyperresponsiveness

Exclusion Criteria:

• unable to give informed consent
• Active smoking < (less than) 6 months from baseline visit
• Concomitant use of dupilumab within 6 months of baseline visit
• pregnant or breastfeeding woman
• in CRSwNP group: current use of asthma medication, eGPA
• in healthy controls: chronic use of local anti-inflammatory agents
• in healthy controls: use of immunosuppressive medication
• in healthy controls: use of antibiotics within the last month (before start study/screening/)

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
eGPA; Eosinophilic granulomatosis with polyangiitis patients before and after treatment with mepolizumab will be compared	Diagnostic test: laboratory experiments before and after mepolizumab treatment; Patients that start with mepolizumab treatment on the basis of the clinical disease course will be measured prior and after start of mepolizumab to evaluate the effects this medication has on various immunological parameters and microbiome
GPA; Comparator group not treated with mepolizumab	Diagnostic test: laboratory experiments before and after mepolizumab treatment; Patients that start with mepolizumab treatment on the basis of the clinical disease course will be measured prior and after start of mepolizumab to evaluate the effects this medication has on various immunological parameters and microbiome
Asthma; Asthma patients before and after treatment with mepolizumab	Diagnostic test: laboratory experiments before and after mepolizumab treatment; Patients that start with mepolizumab treatment on the basis of the clinical disease course will be measured prior and after start of mepolizumab to evaluate the effects this medication has on various immunological parameters and microbiome
CRSwNP; Chronic rhinosinusitis patients before and after treatment with mepolizumab	Diagnostic test: laboratory experiments before and after mepolizumab treatment; Patients that start with mepolizumab treatment on the basis of the clinical disease course will be measured prior and after start of mepolizumab to evaluate the effects this medication has on various immunological parameters and microbiome
Healthy; Healthy comparator group	Diagnostic test: laboratory experiments before and after mepolizumab treatment; Patients that start with mepolizumab treatment on the basis of the clinical disease course will be measured prior and after start of mepolizumab to evaluate the effects this medication has on various immunological parameters and microbiome

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effect mepolizumab treatment has on the nasal microbiome profiles	Paired change in microbiome diversity index for patients treated with mepolizumab.	three months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory evaluation of between group differences	Microbiome and immunological gene expression values will be measured and differential expression analysis will be performed	Through study completion, an average of two years
Mepolizumab effect on outcome 2	The effect mepolizumab treatment has on the immunological gene expression will be measured by differential gene expression analysis.	Through study completion, an average of two years
s there a correlation between the disease activity, the quality of life and the microbiome and immune parameters?	Spearman ranks correlation	Through study completion, an average of two years

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Collaborators: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: February 5, 2024
• First Submitted That Met QC Criteria: February 29, 2024
• First Posted (Actual): March 7, 2024

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Respiratory Tract Diseases; Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Autoimmune Diseases; Lung Diseases; Vasculitis; Skin Diseases, Vascular; Lung Diseases, Interstitial; Systemic Vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Granuloma; Granulomatosis with Polyangiitis; Churg-Strauss Syndrome
• Other Study ID Numbers: NL83176.042.23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Fully anonymized data will be made available for other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No