Eosinophil Subpopulations in Eosinophilic-associated Diseases

NCT06911775 | Not Yet Recruiting

• 1 other identifier: 26188-OSS
• Study Type: observational
• Target: 160
• Locations: 0 countries
• Sites: N/A

Brief Summary

This single-center, non-commercial study will involve 160 participants (80 with eosinophilic asthma (EA), 30 with eosinophilic granulomatosis with polyangiitis (EGPA), 25 with hypereosinophilic syndrome (HES), and 25 healthy donors) to investigate eosinophil subpopulations in these diseases. The study will run from Q4 2024 to Q4 2026. Objectives: Primary: To verify two eosinophil subpopulations (iEos and rEos) in EGPA and HES and analyze the role of type 2 cytokines on their plasticity. Secondary: Compare iEos proportion between different eosinophilic diseases and correlate with disease severity. Exploratory: Assess the effect of mepolizumab on eosinophil subpopulations in vitro. Population: Adults aged 18-75 with EA, EGPA, or HES, and healthy controls. EA patients must have \>300 eosinophils/mcL, EGPA requires asthma + eosinophilia + other specific features, and HES requires high eosinophil counts (\>1500 cells/mL). Methods: Data will be analyzed using Mann-Whitney U, ANOVA, and Spearman correlation tests, with results presented as mean ± SEM. This study will help explore eosinophil behavior in eosinophilic diseases and evaluate mepolizumab's effects on these cells.

Conditions

Eosinophilic Asthma; Eosinophilic Granulomatosis With Polyangiitis (EGPA); Hypereosinophilic Syndrome (HES)

Keywords

Eosinophils; EGPA; HES; EA; Eosinophilic asthma; Eosinophil subpopulations; Flowcytometry; Biomarker; Asthma severity; EGPA severity

Outcome Measures

Primary Outcomes (2)

• Primary objective: first outcome measure

  1\) Proportion of circulating Siglec8+CD16-CD62Llow (iEos) and Siglec8+CD16-CD62Lbright (rEos) cells in bio- naïve, EGPA and HES patients

  From the enrollment of the first patient at 20 months

• Primary objective: second outcome measure

  2\) Modification of the expression of CD62L on peripheral eosinophils upon in vitro stimulation with IL-5, IL-3, GM-CSF, IL-4, IL-13

  From the enrollment of the first patient at 20 months

Secondary Outcomes (2)

• Secondary objective: first outcome measure

  From the enrollment of the first patient at 18 months

• Secondary objective: second outcome measure

  From the enrollment of the first patient at 18 months

Other Outcomes (1)

• Explorative objective

  From month 7 to month 20

Study Arms (4)

Healthy donors

25 healthy subject

EA

80 eosinophilic asthma patients

EGPA

30 EGPA patients

HES

25 HES patients

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Each subject should meet all of the inclusion criteria and none of the exclusion criteria for this study. Under no circumstances can there be exceptions to this rule.

You may qualify if:

• Patients with Asthma, or EGPA or HES:
• Age between 18 and 75 years at the time of signing the informed consent
• Patients with EA, EGPA or HES
• Provision of signed and dated written informed consent form prior to any mandatory study procedures, sampling and analysis.
• Healthy donors:
• \. Age between18 and 75 years healthy donors

You may not qualify if:

• Presence of other chronic pulmonary diseases including COPD
• Presence of other chronic immuno-mediated inflammatory diseases
• Treatment with oral prednisone or equivalent \> 7.5 mg/day
• Treatment with long-acting depot corticosteroids in the last three months
• Use of immunosuppressive medications (cyclosporine A; azathioprine; methotrexate; mycophenolate mofetil)
• Receipt of live attenuated vaccines 30 days prior to the enrollment
• Acute upper or lower respiratory infections within 30 days prior to the date informed consent is obtained or during the screening/run-in period.
• A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with, or has failed to respond to, standard of care therapy
• Subjects who are pregnant or breastfeeding
• Current smoking
• Any clinically significant abnormal findings in physical examination, vital signs, hematology, or clinical chemistry during screening period, which in the opinion of the investigator may put the patient at risk of his/her participation in the study, or may influence the results of the study, or the patient\'s ability to complete entire duration of the study.
• Concurrent enrolment in another interventional or post-authorization safety study.

Sponsors & Collaborators

• University of Florence: lead
• GlaxoSmithKline: collaborator

Related Publications (6)

• Matucci A, Nencini F, Maggiore G, Chiccoli F, Accinno M, Vivarelli E, Bruno C, Locatello LG, Palomba A, Nucci E, Mecheri V, Perlato M, Rossi O, Parronchi P, Maggi E, Gallo O, Vultaggio A. High proportion of inflammatory CD62Llow eosinophils in blood and nasal polyps of severe asthma patients. Clin Exp Allergy. 2023 Jan;53(1):78-87. doi: 10.1111/cea.14153. Epub 2022 May 4.

  PMID: 35490414 BACKGROUND

• Januskevicius A, Jurkeviciute E, Janulaityte I, Kalinauskaite-Zukauske V, Miliauskas S, Malakauskas K. Blood Eosinophils Subtypes and Their Survivability in Asthma Patients. Cells. 2020 May 18;9(5):1248. doi: 10.3390/cells9051248.

  PMID: 32443594 BACKGROUND

• Xenakis JJ, Howard ED, Smith KM, Olbrich CL, Huang Y, Anketell D, Maldonado S, Cornwell EW, Spencer LA. Resident intestinal eosinophils constitutively express antigen presentation markers and include two phenotypically distinct subsets of eosinophils. Immunology. 2018 Jun;154(2):298-308. doi: 10.1111/imm.12885. Epub 2018 Jan 21.

  PMID: 29281125 BACKGROUND

• Marichal T, Mesnil C, Bureau F. Homeostatic Eosinophils: Characteristics and Functions. Front Med (Lausanne). 2017 Jul 11;4:101. doi: 10.3389/fmed.2017.00101. eCollection 2017.

  PMID: 28744457 BACKGROUND

• Mesnil C, Raulier S, Paulissen G, Xiao X, Birrell MA, Pirottin D, Janss T, Starkl P, Ramery E, Henket M, Schleich FN, Radermecker M, Thielemans K, Gillet L, Thiry M, Belvisi MG, Louis R, Desmet C, Marichal T, Bureau F. Lung-resident eosinophils represent a distinct regulatory eosinophil subset. J Clin Invest. 2016 Sep 1;126(9):3279-95. doi: 10.1172/JCI85664. Epub 2016 Aug 22.

  PMID: 27548519 BACKGROUND

• Rosenberg HF, Dyer KD, Foster PS. Eosinophils: changing perspectives in health and disease. Nat Rev Immunol. 2013 Jan;13(1):9-22. doi: 10.1038/nri3341. Epub 2012 Nov 16.

  PMID: 23154224 BACKGROUND

MeSH Terms

Conditions

Pulmonary Eosinophilia; Churg-Strauss Syndrome; Hypereosinophilic Syndrome

Condition Hierarchy (Ancestors)

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

Study Design

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

Study Record Dates

• First Submitted: March 21, 2025
• First Posted: April 4, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 4, 2025

Record last verified: 2025-03