Clinical trial NCT06298448: eGPA and Local Inflammation Within the Ear, Nose and Throat Area
Official title: Impact of Mepolizumab Treatment on the Nasal Microbiome and Local and Systemic Immune Response in Eosinophilic Granulomatosis With Polyangitis (eGPA)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: EGPA - Eosinophilic Granulomatosis With Polyangiitis
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2024-03-07
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with eosinophil driven inflammation for which mepolizumab might be considered for treatment

Brief summary: 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.

Detailed description: See Brief summary.

Eligibility criteria: 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/)

Primary outcomes:
measure: The effect mepolizumab treatment has on the nasal microbiome profiles
timeFrame: three months
Secondary outcomes:
Other outcomes:
measure: Exploratory evaluation of between group differences
timeFrame: Through study completion, an average of two years
measure: Mepolizumab effect on outcome 2
timeFrame: Through study completion, an average of two years
measure: s there a correlation between the disease activity, the quality of life and the microbiome and immune parameters?
timeFrame: Through study completion, an average of two years
Locations:
city: Groningen
country: Netherlands
facility: UMC Groningen
Study officials:
References: