Autoimmune and Inflammatory Response Biomarkers in Fabry Disease

NCT06007768 | Completed

• 1 other identifier: 284/21
• Study Type: observational
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to understand the immune response in Fabry disease (FD). We want to find out how the immune response is related to the severity of FD and how it affects patients' quality of life and pain. Main Questions the Study Aims to Answer:

• How are immune response markers linked to the health of FD patients?
• How is the immune response different between FD patients and healthy individuals? Participants: We will include 20 patients who have FD and are older than 18, and do not have other autoimmune or autoinflammatory diseases. We'll also include a comparison group of the same size who don't have FD, but are similar in age and sex to the FD group. Participants with Fabry disease will be asked about their medical history and complete questionnaires. We will measure their vital signs and collect blood samples to study immune response markers. We'll also look at specific biomarkers related to FD. Healthy participants will do similar tasks for comparison. Comparison: Researchers will compare the immune response markers and other measurements between FD patients and healthy individuals to understand the differences and similarities. Duration: The study will take place over 18 months to gather comprehensive information.

Conditions

Fabry Disease

Keywords

Fabry Disease; Immune response; Biomarkers; Quality of life; Inflammation

Outcome Measures

Primary Outcomes (5)

• High-sensitivity C-reactive protein (hsCRP)

  High-sensitivity C-reactive protein (hsCRP), measured in mg/L.

  Day 1 (one cross-sectional examination only)

• Tumor necrosis factor (TNF)

  Tumor necrosis factor (TNF), measured in pg/mL.

  Day 1 (one cross-sectional examination only)

• Interleukin 6 (IL-6)

  Interleukin 6 (IL-6), measured in pg/mL.

  Day 1 (one cross-sectional examination only)

• Interferon gamma (IFN-γ)

  Interferon gamma (IFN-γ), measured in pg/mL.

  Day 1 (one cross-sectional examination only)

• Vascular cell adhesion protein 1 (VCAM-1)

  Vascular cell adhesion protein 1 (VCAM-1), measured in ng/mL.

  Day 1 (one cross-sectional examination only)

Secondary Outcomes (7)

• Globotriaosylsphingosine (Lyso-Gb3)

  Day 1 (one cross-sectional examination only)

• Brain natriuretic peptide (BNP)

  Day 1 (one cross-sectional examination only)

• N-terminal prohormone of brain natriuretic peptide (NT-proBNP)

  Day 1 (one cross-sectional examination only)

• Cystatin C

  Day 1 (one cross-sectional examination only)

• EuroQol Health-Related Quality of Life (EQ-5D-5L)

  Day 1 (one cross-sectional examination only)

Study Arms (2)

Fabry Disease

Patients with Fabry disease, older than 18 years, and without autoimmune or autoinflammatory diseases.

Control

Subjects without Fabry disease or autoimmune/autoinflammatory diseases, matched for age (± 5 years) and sex.

Eligibility Criteria

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

Study Population

Population of consecutive patients with Fabry Disease (FD) under follow-up in the Internal Medicine Department of the Hospital Universitario Ramon y Cajal. In addition, a Control group of subjects without Fabry disease will be included, among those who come to donate blood at the Hospital Universitario Ramón y Cajal. Controls will be matched for age (± 5 years) and sex with FD patients.

You may qualify if:

• Age ≥ 18 years.
• Diagnosis of Fabry disease (enzymatic or genetic).
• Having signed the informed consent, after having received all the information concerning the study.

You may not qualify if:

• Autoimmune or autoinflammatory disease or patients with transplanted organs (corneal transplant excluded) and under additional immunosuppressive treatment.
• Serious intercurrent diseases such as HIV, COVID-19, cancer under active treatment, severe anemia, severe hepatic, respiratory or renal failure, or other pathologies that, at the investigator's discretion, could interfere with the objectives of the study.
• For the Control group:

Sponsors & Collaborators

• Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal: lead
• Fundación Mutua Madrileña: collaborator

Study Sites (1)

Hospital Universitario Ramón y Cajal

Madrid, Madrid, 28034, Spain

Location

Related Publications (11)

• Rozenfeld P, Feriozzi S. Contribution of inflammatory pathways to Fabry disease pathogenesis. Mol Genet Metab. 2017 Nov;122(3):19-27. doi: 10.1016/j.ymgme.2017.09.004. Epub 2017 Sep 13.

  PMID: 28947349 BACKGROUND

• De Francesco PN, Mucci JM, Ceci R, Fossati CA, Rozenfeld PA. Fabry disease peripheral blood immune cells release inflammatory cytokines: role of globotriaosylceramide. Mol Genet Metab. 2013 May;109(1):93-9. doi: 10.1016/j.ymgme.2013.02.003. Epub 2013 Feb 13.

  PMID: 23452955 BACKGROUND

• Mauhin W, Lidove O, Masat E, Mingozzi F, Mariampillai K, Ziza JM, Benveniste O. Innate and Adaptive Immune Response in Fabry Disease. JIMD Rep. 2015;22:1-10. doi: 10.1007/8904_2014_371. Epub 2015 Feb 18.

  PMID: 25690728 BACKGROUND

• Ge W, Li D, Gao Y, Cao X. The Roles of Lysosomes in Inflammation and Autoimmune Diseases. Int Rev Immunol. 2015;34(5):415-31. doi: 10.3109/08830185.2014.936587. Epub 2014 Jul 30.

  PMID: 25075736 BACKGROUND

• Simonetta I, Tuttolomondo A, Daidone M, Pinto A. Biomarkers in Anderson-Fabry Disease. Int J Mol Sci. 2020 Oct 29;21(21):8080. doi: 10.3390/ijms21218080.

  PMID: 33138098 BACKGROUND

• Loso J, Lund N, Avanesov M, Muschol N, Lezius S, Cordts K, Schwedhelm E, Patten M. Serum Biomarkers of Endothelial Dysfunction in Fabry Associated Cardiomyopathy. Front Cardiovasc Med. 2018 Aug 15;5:108. doi: 10.3389/fcvm.2018.00108. eCollection 2018.

  PMID: 30159316 BACKGROUND

• Shen JS, Meng XL, Moore DF, Quirk JM, Shayman JA, Schiffmann R, Kaneski CR. Globotriaosylceramide induces oxidative stress and up-regulates cell adhesion molecule expression in Fabry disease endothelial cells. Mol Genet Metab. 2008 Nov;95(3):163-8. doi: 10.1016/j.ymgme.2008.06.016. Epub 2008 Aug 15.

  PMID: 18707907 BACKGROUND

• Weidemann F, Beer M, Kralewski M, Siwy J, Kampmann C. Early detection of organ involvement in Fabry disease by biomarker assessment in conjunction with LGE cardiac MRI: results from the SOPHIA study. Mol Genet Metab. 2019 Feb;126(2):169-182. doi: 10.1016/j.ymgme.2018.11.005. Epub 2018 Nov 12.

  PMID: 30594474 BACKGROUND

• Chimenti C, Scopelliti F, Vulpis E, Tafani M, Villanova L, Verardo R, De Paulis R, Russo MA, Frustaci A. Increased oxidative stress contributes to cardiomyocyte dysfunction and death in patients with Fabry disease cardiomyopathy. Hum Pathol. 2015 Nov;46(11):1760-8. doi: 10.1016/j.humpath.2015.07.017. Epub 2015 Aug 4.

  PMID: 26362204 BACKGROUND

• Yogasundaram H, Nikhanj A, Putko BN, Boutin M, Jain-Ghai S, Khan A, Auray-Blais C, West ML, Oudit GY. Elevated Inflammatory Plasma Biomarkers in Patients With Fabry Disease: A Critical Link to Heart Failure With Preserved Ejection Fraction. J Am Heart Assoc. 2018 Nov 6;7(21):e009098. doi: 10.1161/JAHA.118.009098.

  PMID: 30571380 BACKGROUND

• Chen KH, Chien Y, Wang KL, Leu HB, Hsiao CY, Lai YH, Wang CY, Chang YL, Lin SJ, Niu DM, Chiou SH, Yu WC. Evaluation of Proinflammatory Prognostic Biomarkers for Fabry Cardiomyopathy With Enzyme Replacement Therapy. Can J Cardiol. 2016 Oct;32(10):1221.e1-1221.e9. doi: 10.1016/j.cjca.2015.10.033. Epub 2015 Nov 10.

  PMID: 26919792 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Serum, plasma (EDTA and lithium heparin) and peripheral blood mononuclear cells.

MeSH Terms

Conditions

Fabry Disease; Inflammation

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Monica A Lopez Rodriguez, MD PhD

  Hospital Universitario Ramon y Cajal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2023
• First Posted: August 23, 2023
• Study Start: September 20, 2022
• Primary Completion: April 27, 2023
• Study Completion: April 27, 2023
• Last Updated: March 17, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data will be made available one year after publication of the main results, during 5 years.
• Access Criteria: Data will be available for sharing with investigators seeking to verify analyses or to conduct additional analyses that are appropriate to the nature of these data. Data will be made available for sharing upon request.

Locations

ES (1)