Natural History and Structural Functional Relationships in Fabry Renal Disease Treatment Outcomes(Changes)in Fabry Renal Disease Study

NCT01581424 | Recruiting

• 2 other identifiers: 100349U54NS065768
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

The investigators will perform a study with two major components. The first is a natural history study of untreated Fabry patients. This study component will detail kidney microscopic structural changes in Fabry patients before starting enzyme replacement therapy and will correlate these changes with kidney function, including glomerular filtration rate and urinary albumin excretion rate. The investigators will perform studies on samples obtained at baseline, or before enzyme replacement therapy is initiated. The goal of our study is to find kidney microscopic changes in the biopsies that are associated with kidney disfunction. Our hypotheses for this study are:

1. 1.Much of the natural history of Fabry renal structural changes will occur without detectable renal functional alterations.
2. 2.Structural changes associated with the initial onset of proteinuria and those associated with the subsequent progressive loss of filtration function will differ and will be best described by non-linear models.
3. 3.There will be sufficient precision of Fabry renal structural-functional relationships to support renal structure as an acceptable clinical trial surrogate endpoint for later renal functional deterioration.
4. 4.Enzyme Replacement Therapy(ERT) instituted at younger ages is more effective in reducing podocytes(PC),distal tubular cells(DTC),and arterial smooth muscle cells (ASMC)GL-3 than in older Fabry patients.
5. 5.Earlier institution of ERT will stabilize PC numbers while later ERT institution, especially in proteinuric adults, may not prevent progressive decline in PC numbers and associated glomerular sclerosis, tubulointerstitial injury, and GFR loss.
6. 6.Whereas lower ERT dose may effectively clear GL-3 from endothelial and mesangial cells, it will be less effective in clearing GL-3 from PC and also from DTC and ASMC.
7. 7.Affected cells will be cleared of GL-3 equivalently in females and males.

Conditions

Fabry Disease

Keywords

Fabry disease; kidney function; kidney structure morphometry; Fabry kidney disease; Podocytes

Outcome Measures

Primary Outcomes (1)

• Natural History and Determinants of Renal Structural Responses (Changes) to Enzyme Replacement Therapy in Fabry Disease

  Renal function measurements for the cross sectional natural history component will be urine protein excretion and measured/estimated GFR. Renal biopsies will provide estimates of the amount of GL-3 in various kidney structures. We will determine which structural parameter or composite of structural parameters is most closely associated with kidney function. For renal structural responses (changes) with ERT the primary outcome will the magnitude of reduction in podocyte GL-3 per glomerulus after (a)5 months, (b) 11 months, and (c) 60 months of ERT.

  Natural history component, cross sectional; ERT component, 5, 11, and 60 months

Secondary Outcomes (1)

• Natural History and Determinants of Renal Structural Responses (Changes) to Enzyme Replacement Therapy in Fabry Disease

  Baseline, 5, 11 and 60 months

Eligibility Criteria

• Age: 1 Year - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

50-60 male and female adults and children with Fabry disease who either have or have not been initiated on enzyme replacement therapy, and whose physicians have determined that a kidney biopsy and renal functional studies are clinically indicated before initiation of enzyme replacement therapy and as follow-up for this therapy or who have completed clinical trials of ERT, have baseline or baseline and and follow biopsies, and have consented to allow their tissues to be examined for research purposes. We are expecting to recruit patients from many different centers.

You may qualify if:

• Patients diagnosed with Fabry disease who have/have not received enzyme replacement therapy where a clinical decision has been made to obtain a kidney biopsy, a GFR, and urinary albumin studies or where patients have previously completed clinical trials which included measures of renal function and renal biopsies.

You may not qualify if:

• Patients with serum creatinine more than 2.5 mg/dL or known to have a renal disease other than Fabry.

Sponsors & Collaborators

• University of Minnesota: lead
• Rare Diseases Clinical Research Network: collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Washington University School of Medicine: collaborator
• Haukeland University Hospital: collaborator

Study Sites (2)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

Universtity of Minnesota, Department of Pediatric Nephrology

Minneapolis, Minnesota, 55455, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum and Plasma samples as well as urine samples from an overnight collection.

MeSH Terms

Conditions

Fabry Disease

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

Study Officials

• Chet Whitley, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

• Michael Mauer, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael Mauer, MD

CONTACT

612-626-2720; mauer002@umn.edu

Study Design

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

Study Record Dates

• First Submitted: January 17, 2012
• First Posted: April 20, 2012
• Study Start: October 1, 2010
• Primary Completion (Estimated): July 31, 2030
• Study Completion (Estimated): July 31, 2030
• Last Updated: August 22, 2025

Record last verified: 2025-08

Locations

US (2)