Subtypes and Prognostic Factors in Erdheim-Chester Disease

NCT06317246 | Recruiting

• 1 other identifier: ECDSUB
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 2

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

Outcome Measures

Primary Outcomes (2)

• Clinical characteristics of patients with Erdheim-Chester Disease

  Evaluation of clinical characteristics in extreme subtypes of Erdheim-Chester Disease

  4 years

• Prognostic factors of patients with Erdheim-Chester Disease

  Evaluation of prognostic factors in extreme subtypes of Erdheim-Chester Disease

  4 years

Study Arms (1)

Investigation of BRAF mosaicism

EXPERIMENTAL

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

Genetic: Investigation of BRAF mosaicism

Interventions

Investigation of BRAF mosaicism 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

Investigation of BRAF mosaicism

Eligibility Criteria

• Age: 1 Year - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Meyer Children's Hospital IRCCS: lead

Study Sites (2)

Meyer Children's Hospital IRCCS

Florence, Firenze, Italy

RECRUITING

AOU Parma

Parma, Italy

RECRUITING

MeSH Terms

Conditions

Erdheim-Chester Disease

Condition Hierarchy (Ancestors)

Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Augusto Vaglio

CONTACT

3200026532; augusto.vaglio@meyer.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Nephrology, Principal Investigator

Study Record Dates

• First Submitted: February 21, 2024
• First Posted: March 19, 2024
• Study Start: September 15, 2020
• Primary Completion: September 15, 2024
• Study Completion: December 15, 2024
• Last Updated: March 19, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)