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

EGPA - Eosinophilic Granulomatosis With Polyangiitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06298448
• Other study ID #: NL83176.042.23
• Status: Recruiting
• Start date: February 14, 2024
• Est. completion date: December 2028

Study information

• Verified date: February 2024
• Source: University Medical Center Groningen
• Contact: Abraham Rutgers, MD-PhD
• Phone: +31503616161
• Email: a.rutgers[@]umcg.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

See Brief summary.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 2028
• Est. primary completion date: December 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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/)

Related Conditions & MeSH terms

• Churg-Strauss Syndrome
• EGPA - Eosinophilic Granulomatosis With Polyangiitis
• Granulomatosis with Polyangiitis

Intervention

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

Locations

Country	Name	City	State
Netherlands	UMC Groningen	Groningen

Sponsors (2)

Lead Sponsor	Collaborator
University Medical Center Groningen	GlaxoSmithKline

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Primary	The effect mepolizumab treatment has on the nasal microbiome profiles	Paired change in microbiome diversity index for patients treated with mepolizumab.	three months