Cardiovasculorenal Phenotyping in Fabry Disease Through Noninvasive Testing

NCT05699265 | Terminated

• 1 other identifier: 2021-0779 VDFP
• Study Type: observational
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Fabry Disease

Outcome Measures

Primary Outcomes (1)

• Peak systolic blood pressure

  The mean peak systolic blood pressure for Fabry disease patients is assumed to be 160 mmHg

  through study completion, approximately 22 months

Study Arms (1)

Fabry Disease Follow-Up Patients

Diagnostic Test: Measures of arterial stiffness and endothelial function; Diagnostic Test: Ambulatory blood pressure monitoring; Diagnostic Test: Cardiopulmonary exercise testing (CPET); Diagnostic Test: Serum and urine biomarkers

Interventions

Measures of arterial stiffness and endothelial function DIAGNOSTIC_TEST

baseline cMRI, vascular reactivity studies, and CPET

Fabry Disease Follow-Up Patients

Ambulatory blood pressure monitoring DIAGNOSTIC_TEST

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).

Fabry Disease Follow-Up Patients

Cardiopulmonary exercise testing (CPET) DIAGNOSTIC_TEST

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.

Fabry Disease Follow-Up Patients

Serum and urine biomarkers DIAGNOSTIC_TEST

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.

Fabry Disease Follow-Up Patients

Eligibility Criteria

• Age: 8 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants to be included in this study are patients who are being seen for follow up of known Fabry disease. These patients are screened regularly by the Department of Human Genetics for routine Fabry disease care. All Fabry disease patients who are physically able have a baseline cMRI and CPET performed at their appointment, per local standard of care.

You may qualify if:

• 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

You may not qualify if:

• Physical limitation that would preclude exercise
• Currently prescribed non-ERT treatments for Fabry disease

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Sanofi: collaborator

Study Sites (1)

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Fabry Disease

Interventions

Blood Pressure Monitoring, Ambulatory; Exercise Test

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

Intervention Hierarchy (Ancestors)

Blood Pressure Determination; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Monitoring, Ambulatory; Monitoring, Physiologic; Heart Function Tests; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Ergometry; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2023
• First Posted: January 26, 2023
• Study Start: February 1, 2023
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2025
• Last Updated: June 19, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)