Inflammatory Pathways and Cardiac Growth Factors Associated With Fabry Disease Cardiomyopathy
1 other identifier
observational
50
1 country
1
Brief Summary
In Fabry disease (FD), α-galactosidase A deficiency leads to the accumulation of globotriaosylceramide (Lyso-Gb3 and Gb3), triggering a pathologic cascade that causes progressive damage to multiple organs, including the heart. The heart is one of the organs that is very sensitive to the deficiency of α-galactosidase A. There is a subgroup of patients with significant residual α-galactosidase activity and a phenotype with primary cardiac involvement, occasionally referred as "cardiac variant." The manifestations of cardiac involvement in FD are left ventricular hypertrophy (LVH), diastolic dysfunction, microvascular angina. Cardiac hypertrophy is the most common cardiac pathology and cause of death in patients with FD. The elevation of the inflammatory markers strongly demonstrates that chronic inflammation drives the cardiovascular pathophysiology in FD. Moreover, plasma TNF, TNFR2, Il-6 specifically elevated in FD patients with cardio hypertrophy. The chronic inflammation in combination with elevated Lyso-Gb3 further drives the FD progression even under therapy. The expression of the endothelial-cardiomyocyte growth factors will change in response to chronic inflammation during the development of cardiac hypertrophy. This is a clinical observational study designed to identify the role of inflammatory signaling markers and secreted growth factors in the progression of cardiac pathology in FD
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for all trials
Started Dec 2020
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2020
CompletedFirst Submitted
Initial submission to the registry
January 21, 2021
CompletedFirst Posted
Study publicly available on registry
January 26, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2022
CompletedJanuary 27, 2021
January 1, 2021
1.4 years
January 21, 2021
January 25, 2021
Conditions
Outcome Measures
Primary Outcomes (1)
Identify blood-based biomarkers for early detection of cardiac involvement in Fabry disease
inflammatory markers and growth factors in blood and urine samples. Biomarkers: NF-kB, IL-2, Il-10, MCP-1,IGN-gamma, PIGF, IGF-1, TNFR, VEGF, TGF-betta, TNF-alpha, CM-CFS, Il-1a, Il-1b, Il-6.
18 months
Study Arms (3)
Fabry Disease subjects with cardiomyopathy
Patients (males and females) with confirmed Fabry disease, with clinical cardiac involvement based on results of structural imaging (cardiac echocardiography and MRI).
Fabry Disease subjects without cardiomyopathy
Patients (males and females) with confirmed Fabry disease, without clinical cardiac involvement based on results of structural imaging (cardiac echocardiography and MRI).
Healthy control
The control group will consist of age-and gender-matched healthy individuals.
Interventions
new diagnostic biomarkers
Eligibility Criteria
Patients (males and females) with confirmed Fabry disease, with and without clinical cardiac involvement based on results of structural imaging (cardiac echocardiography and MRI), will be included in the study. The control group will consist of age-and gender-matched healthy individuals. Cardiac involvement will be assessed using the available clinical imaging and laboratory data. The study will involve 30 ages-and gender-matched subjects divided into the following cohorts.
You may qualify if:
- approved informed consent signed by the patients,
- Confirmed diagnosis of Fabry disease based on deficient α-Gal A enzymatic activity and molecular analysis demonstrating pathogenic variants in the GLA gene
- Male and Female, ages 18-70.
You may not qualify if:
- Any other known genetic condition associated with HCM,
- Evidence of hepatitis B or C infections or other chronic infectious diseases,
- Pregnancy or breastfeeding.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Lysosomal and Rare disorder research and treatment center
Fairfax, Virginia, 22030, United States
Related Publications (1)
Ivanova MM, Dao J, Friedman A, Kasaci N, Goker-Alpan O. Sex Differences in Circulating Inflammatory, Immune, and Tissue Growth Markers Associated with Fabry Disease-Related Cardiomyopathy. Cells. 2025 Feb 20;14(5):322. doi: 10.3390/cells14050322.
PMID: 40072051DERIVED
Biospecimen
blood, urine
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ozlem Goker-ALpan, MD
Lysosomal and Rare Disorders Research and Treatment Center
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 21, 2021
First Posted
January 26, 2021
Study Start
December 1, 2020
Primary Completion
May 1, 2022
Study Completion
August 1, 2022
Last Updated
January 27, 2021
Record last verified: 2021-01
Data Sharing
- IPD Sharing
- Will not share