The Epigenomic Signature of Eosinophilic Granulomatosis With Polyangiitis

NCT06231498 | Not Yet Recruiting

• 1 other identifier: EPI-EGPA
• Study Type: observational
• Target: 300
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a case-control observational study on blood samples. The primary goal of this study is to identify the epigenetic marks that can distinguish patients suffering from Eosinophilic Granulomatosis with Polyangiitis (EGPA) from healthy individuals. The secondary goal is to identify epigenetic or transcriptional marks that can predict if a patient with EGPA will benefit from therapy with Mepolizumab. This study is observational, meaning there will be no alterations of patients' routine clinical care. A blood sample will be drawn for each patient. If the patient will undergo treatment with Mepolizumab (based on routine clinical care), then the blood sample will be drawn before Mepolizumab initiation. The blood samples will be used for genome-wide DNA methylation profiling and for transcriptomic profiling. Healthy individuals as controls for the association study will not be recruited. In fact, the epigenetic and transcriptomic data obtained from EGPA patient blood will be compared against already available genome-wide DNA methylation and transcriptomic profiles of the blood of healthy individuals from previous studies. A total of 300 patients with EGPA will be recruited for the study. The first part of the study, corresponding to the primary goal, will involve all of the 300 patients. The second part of the study, corresponding to the secondary goal, will involve a study population subset consisting of 50 patients.

Conditions

Eosinophilic Granulomatosis With Polyangiitis

Keywords

Epigenome; DNA Methylation; Eosinophilic Granulomatosis with Polyangiitis; EGPA

Outcome Measures

Primary Outcomes (2)

• Epigenome-Wide Association Study

  The primary objective of the study is the identification of loci whose methylation level is associated with the pathology (i.e. epigenetic markers of the disease). This means that there is not any outcome that will be measured with regard to the primary objective.

  Through study completion, an average of 1 year

• Mepolizumab Therapy Response

  The main secondary objective of the study is the identification of loci whose methylation level correlates with the response to treatment with the Mepolizumab in patients with EGPA (i.e. epigenetic predictors of response to Mepolizumab). To this end, the response to treatment with Mepolizumab is the outcome that will be measured. Complete response to treatment will be defined as no disease activity (Birmingham Vasculitis Activity Score = 0) and a prednisolone or prednisone dose (or equivalent) of ≤4.0 mg/day, as defined by the MIRRA trial. Partial response to treatment will be defined as no disease activity and a prednisone dose (or equivalent) of \>4.0 mg/day.

  6 months and 12 months after Mepolizumab therapy initiation

Study Arms (1)

Overall Cohort

The study will include 300 adult (\>18yo) patients with Eosinophilic Granulomatosis with Polyangiitis (EGPA). All patients will be recruited at Meyer Children's Hospital and Careggi University Hospital, which are referral centers for EGPA and have a large cohort of prevalent cases under long-term follow-up. They will represent the cases for the case-control epigenome-wide association study. Patients are expected to be untreated or under glucocorticoids at the time of sampling. A blood sample will be drawn for each participant. Among this cohort, 50 patients will be identified that will undergo treatment with Mepolizumab, and they will form the sub-cohort in which we will search for epigenetic predictors of the response to Mepolizumab treatment (predictive epigenomic study). These 50 patients will also be analyzed with regard to the transcriptomic and proteomic profile. Written informed consent from all participants and approval from the local ethical committees will be obtained.

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study will include 300 adult (\>18yo) patients with Eosinophilic Granulomatosis with Polyangiitis (EGPA). All patients will be recruited at Meyer Children's Hospital and Careggi University Hospital, which are referral centres for EGPA and have a large cohort of prevalent cases under long-term follow-up. They will represent the cases for the case-control epigenome-wide association study. Patients are expected to be untreated or under glucocorticoids at the time of sampling. A blood sample will be drawn for each participant. Among this cohort, 50 patients will be identified that will undergo treatment with Mepolizumab, and they will form the sub-cohort in which epigenetic predictors of the response to Mepolizumab treatment (predictive epigenomic study) will be searched for.

You may qualify if:

• Patients over 18 years of age who meet the 1990 American College of Rheumatology classification criteria for EGPA or the criteria proposed in the MIRRA trial, or the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria;
• Written informed consent from all the study participants.

You may not qualify if:

• Patients with inadequate or unavailable data regarding response to treatment at months 6 and 12 after Mepolizumab initiation will be included in the case-control Epigenome-Wide Association Study (EWAS) but not in the predictive epigenomic study;
• Patients with childhood-onset EGPA;
• Patients who are pregnant or breast-feeding.

Sponsors & Collaborators

• Meyer Children's Hospital IRCCS: lead
• Careggi Hospital: collaborator
• University of Florence: collaborator

Biospecimen

Retention: SAMPLES WITH DNA

A peripheral whole blood sample for each patient

MeSH Terms

Conditions

Churg-Strauss Syndrome

Condition Hierarchy (Ancestors)

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Granuloma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Augusto Vaglio, MD, PhD

  Meyer Children's Hospital IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Augusto Vaglio, MD, PhD

CONTACT

+39 0555662905; augusto.vaglio@meyer.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 14, 2023
• First Posted: January 30, 2024
• Study Start: April 1, 2024
• Primary Completion: September 1, 2025
• Study Completion: December 1, 2025
• Last Updated: February 23, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share