NCT05698901

Biomarkers and Cardiac Imaging Diagnostic Assay for Monitoring Patients With Fabry Disease

Recruiting now Last updated 18 November 2023

What this trial tests

trial testing Agalsidase beta in Fabry Disease in 150 participants. Currently enrolling.

Timeline

19 September 2023

Primary endpoint
30 September 2026

30 September 2027

Quick facts

Lead sponsor	Mackay Memorial Hospital
Status	Recruiting now
Study type	OBSERVATIONAL
Enrollment	150
Start date	19 September 2023
Primary completion	30 September 2026
Estimated completion	30 September 2027
Sites	1 location across Taiwan

Drugs / interventions tested

• Agalsidase beta (AGALSIDASE BETA) — full drug profile →

Conditions studied

• Fabry Disease — all drugs for Fabry Disease →

Sponsor

Mackay Memorial Hospital

Who can join

18 and older, any sex, with Fabry Disease. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by deficient activity of the enzyme α-Gal A resulting from mutations affecting the GLA gene.

It is characterized by severe multi-systemic involvement that leads to major organ failure and premature death in affected men and in some women. The α-Gal A deficiency results in progressive accumulation of un-degraded glycosphingolipids, predominantly globotriaosylceramide (Gb3), within cell lysosomes throughout the body.1

In patients at the fourth to fifth decade, left ventricular hypertrophy occur usually, and myocardial infarction and heart failure develops disease progress. Life-threatening renal, cardiac, and cerebrovascular diseases are added in later decades.2,3

Fabry disease is treatable with enzyme replacement therapy (ERT). Early recognition of symptoms and diagnosis of patients at a potentially reversible stage of the disease is therefore important. To date, plasma Lyso-Gb3 is useful in the diagnosis of Fabry disease. All male with classical Fabry disease could be discerned by an elevated plasma Lyso-GL-3; All adult female patients have elevated plasma Lyso-GL-3 above normal range.4 Other study also indicated that higher lyso-Gb3 concentrations at first visit were associated with a higher event rate in the past. Men with classical FD have higher Lyso-GL-3 values compared with patients with non-classical FD and women along with an increased risk of developing complications, more severe cardiac and renal disease.5

According to a publication from Taiwan society of cariology (TSOC) expert consensus, several cardiac biomarkers including N terminal pro B type natriuretic peptide (NT-proBNP) and cardiac troponin I/T (cTNI/cTNT) have been proposed to be alternative surrogate markers of cardiac involvement in FD.6However, there is no study to analyze the relationship between all these biomarkers including lyso-Gb3 and FD cardiac manifestation or improvement of cardiac damage outcomes under ERT yet.

There is a high prevalence of the cardiac variant (IVS4+919G→A) (\~1 in 1600 males) of FD in Taiwan as revealed by newborn screening programs7,8 and patients with idiopathic HCM.9 FD patients with cardiac variant need to fulfill at least two indicators as stated in "cardiac function assessment indicators of Fabry's disease cardiac variant type" with cardiac biopsy confirmed GL3 or lyso-Gb3 lipid accumulation to get local reimbursement for treatment. Cardiac biopsy is an invasive and relative dangerous procedure that some patients would refuse to take this procedure and could not get local reimbursement resulting in delay in treatment.

Therefore in the present study the investigators are aiming to identify candidate biomarkers to establish a scoring algorithm for evaluating Fabry disease progression status or treatment response and the investigators could stage patient who with more correlated biomarkers at baseline would have higher risk to develop sever clinical outcome and initiate early therapy.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Inflammation, Oxidative Stress, and Endothelial Dysfunction in the Pathogenesis of Vascular Damage: Unraveling Novel Cardiovascular Risk Factors in Fabry Disease.
   Faro DC, Di Pino FL, Monte IP. · · 2024 · cited 25× · PMID 39125842 · DOI 10.3390/ijms25158273