Fabry Disease
Conditions
Brief summary
A longitudinal pilot study will be conducted to determine if there are additional testing modalities that are effective in broadly phenotyping subclinical dysfunction in patients with Fabry disease. Individual patients will undergo serial testing over a two-year period to evaluate for changes in their cardiovasculaorenal function during this period. Novel modalities evaluated will include measures of arterial stiffness, ambulatory blood pressure monitoring, cardiopulmonary exercise testing (CPET), and novel serum and urine biomarkers. The benefit of these measures being evaluated is that they are noninvasive, can be performed rapidly, and have reduced costs compared to the current standard screening modalities. Results from these evaluations will be compared to cMRI and standard urine and serum biomarkers performed clinically per local standard of care. The results will also be compared to both published normative data and data from patients with diabetes mellitus, who have a similar microvascular disease process to patients with Fabry disease.
Interventions
DIAGNOSTIC_TESTMeasures of arterial stiffness and endothelial function
baseline cMRI, vascular reactivity studies, and CPET
DIAGNOSTIC_TESTAmbulatory blood pressure monitoring
A manual blood pressure with a mercury sphygmomanometer will be performed in order to have an accurate baseline measurement. The SphygmoCor SCOR-PVx System (Atcor Medical, Syndey, Australia), previously validated in the young, will be used for the assessment of PWV (pulse wave velocity) and the Heart Rate Variability (HRV).
DIAGNOSTIC_TESTCardiopulmonary exercise testing (CPET)
Cardiopulmonary exercise testing will be performed, and the patients will have a baseline oxygen uptake at rest to determine the rates for testing. A 12 lead ECG, heart rate, a 12 lead rhythm strip, and a 6 lead rhythm strip will be recorded. Oxygen consumption and carbon dioxide production will be measured. Blood pressure will be measured. Perceived exertion will be obtained during each workload using the Borg Scale. The results for submaximal effort testing will be derived from completed maximal testing. The outcome measures will be obtained once the subject reaches anaerobic threshold.
DIAGNOSTIC_TESTSerum and urine biomarkers
Clinical labs drawn will include plasma and urine globotriaosylsphingosine (lyso-Gb3), globotriaosylceramide (GL3), blood urea nitrogen, creatinine, cystatin C, urinalysis, urine protein, urine microalbumin and urine creatinine. Labs specific for this study will include N-acetyl-β-glucosaminidase, urine neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule 1 (KIM-1). All data will be obtained at three different time intervals: enrollment, 1 year and 2 years.
Sponsors
Sanofi
Children's Hospital Medical Center, Cincinnati
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
8 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Fabry patients with classical disease * English speaking, which is needed to assist with obtaining a maximal effort CPET * No medical contraindications to cardiopulmonary exercise testing or cMRI * Either treatment naïve or current taking ERT
Exclusion criteria
* Physical limitation that would preclude exercise * Currently prescribed non-ERT treatments for Fabry disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak systolic blood pressure | through study completion, approximately 22 months | The mean peak systolic blood pressure for Fabry disease patients is assumed to be 160 mmHg |
Countries
United States
Outcome results
None listed