Subtypes and Prognostic Factors in Erdheim-Chester Disease

NCT ID: NCT06317246

Last Updated: 2024-03-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-15
• Study Completion Date: 2024-12-15

Brief Summary

Erdheim-Chester Disease (ECD) is a rare form of histiocytosis characterized by the proliferation of blood cells, known as histiocytes, which infiltrate various organs and tissues, often causing irreversible damage. The causes of the pathology are still unknown. Although the disease typically affects adult individuals, cases of pediatric-onset ECD have been described. However, there is a lack of detailed information on the phenotypic characteristics of these patients, and reliable data on response to specific therapies and long-term outcomes are missing. Three patients referred to our reference center for Histiocytosis present a concomitant BRAF-mutated neoplasm. Such an association could be due to the presence of mosaicisms for the BRAF V600E mutation. Mosaicism is a biological event defined as the presence of more than one genetically dissimilar cell population in the same organism and is an increasingly studied field, both in normal and pathological conditions. If proven in ECD as well, this mechanism could contribute to providing answers to the still open questions regarding the development of this disease.

Conditions

Erdheim-Chester Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Investigation of BRAF mosaicism

The study of BRAF mosaicism will be conducted on biopsy samples from patients with ECD and other neoplasms co-occurring with the BRAFV600E mutation. The samples will be labeled with anti-Pu.1-Alexa Fluor 647 antibody (which binds to macrophages), then DNA will be extracted using FACS method and amplified using MDA (Qiagen Repli-G Single-Cell kit). Quality control will be performed using Quant-it (ThermoScientific) and Agilent 4200 TapeStation. Eligible samples will undergo digital droplet PCR (ddPCR) and sequencing. ddPCR probes for wild-type and mutant alleles will be used. Sequencing will be performed using Illumina HiSeq 2500 system

Group Type: EXPERIMENTAL

Investigation of BRAF mosaicism

Intervention Type: GENETIC

The study of BRAF mosaicism will be conducted on biopsy samples from patients with ECD and other neoplasms co-occurring with the BRAFV600E mutation. The samples will be labeled with anti-Pu.1-Alexa Fluor 647 antibody (which binds to macrophages), then DNA will be extracted using FACS method and amplified using MDA (Qiagen Repli-G Single-Cell kit). Quality control will be performed using Quant-it (ThermoScientific) and Agilent 4200 TapeStation. Eligible samples will undergo digital droplet PCR (ddPCR) and sequencing. ddPCR probes for wild-type and mutant alleles will be used. Sequencing will be performed using Illumina HiSeq 2500 system

Interventions

Investigation of BRAF mosaicism

The study of BRAF mosaicism will be conducted on biopsy samples from patients with ECD and other neoplasms co-occurring with the BRAFV600E mutation. The samples will be labeled with anti-Pu.1-Alexa Fluor 647 antibody (which binds to macrophages), then DNA will be extracted using FACS method and amplified using MDA (Qiagen Repli-G Single-Cell kit). Quality control will be performed using Quant-it (ThermoScientific) and Agilent 4200 TapeStation. Eligible samples will undergo digital droplet PCR (ddPCR) and sequencing. ddPCR probes for wild-type and mutant alleles will be used. Sequencing will be performed using Illumina HiSeq 2500 system

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

• Prevalent and incident patients (adults and pediatric), with histologically confirmed diagnosis of Erdheim-Chester Disease according to the latest diagnostic recommendations;
• Signing of informed consent for study participation.

Exclusion Criteria

• Patients for whom clinical and imaging data are not available and for whom it is not possible to retrieve histological samples."

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Meyer Children's Hospital IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Augusto Vaglio

Associate Professor of Nephrology, Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Meyer Children's Hospital IRCCS

Florence, Firenze, Italy

Site Status: RECRUITING

AOU Parma

Parma, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Augusto Vaglio

Role: CONTACT

augusto.vaglio@meyer.it

3200026532

Facility Contacts

Augusto Vaglio

Role: primary

augusto.vaglio@meyer.it

Domenico Corradi

Role: primary

domenico.corradi@unipr.it

Other Identifiers

ECDSUB

Identifier Type: -

Identifier Source: org_study_id