Fabry DiseaseLDN6702NCT01581424
Natural History and Structural Functional Relationships in Fabry Renal Disease Treatment Outcomes(Changes)in Fabry Renal Disease Study
An observational study of Fabry Disease, run by University of Minnesota at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 1 year to 75 years
- Conditions the study is for
- Fabry Disease
- How many people
- 50 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2010to 31 Jul 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- Patients with serum creatinine more than 2.5 mg/dL or known to have a renal disease other than Fabry.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
University of Minnesota
Minneapolis, Minnesota, 55455
Michael Mauer, MD, 612-626-2720, mauer002@umn.edu
- Recruiting
Universtity of Minnesota, Department of Pediatric Nephrology
Minneapolis, Minnesota, 55455
Michael Mauer, MD, 612-626-2720, mauer002@umn.edu
Michael Mauer, MD
About this study
Official title: Natural History and Structural Functional Relationships in Fabry Renal Disease Natural History, Structural Functional Relationships and Determinants of Renal Structural Responses (Changes) With Enzyme Replacement Therapy in Fabry Disease
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:
- Much of the natural history of Fabry renal structural changes will occur without detectable renal functional alterations.
- 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.
- 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.
Read more
The second component examines the effects of age and gender at start of enzyme replacement therapy (ERT), as well as dosage levels of ERT on the renal cellular clearance of GL3 from Fabry patients by comparing baseline to follow-up kidney biopsies performed 5, 11, and 60 months later, with all comparisons matched for ERT treatment duration. Our hypotheses for this component of the study are as follows:
- 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.
- 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.
- 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.
- Affected cells will be cleared of GL-3 equivalently in females and males.
Read the detailed description
Fabry disease is a rare genetic disease with deficient activity of enzyme alpha-galactosidase A. Deficient activity of this enzyme leads to the accumulation of lipid-derived inclusions in different organs including kidney, heart and vessels. These inclusions can be found in the kidney even before birth. The earliest known clinical manifestation of Fabry kidney disease is the appearance of excess protein in the urine, which usually occurs in the second decade of life. However, our studies, as well as those of other investigators show evidence that kidney injury starts much earlier. Once excess protein is found in the urine, kidney function deterioration becomes progressive, and most Fabry patients require kidney transplantation or hemodialysis in the third to fifth decade of life. The lesion or composite of lesions responsible for functional deterioration of the kidney in Fabry disease are not well known. Their delineation using quantitative, unbiased, morphometric methods will help to understand this disease, and to develop surrogate structural outcomes for early intervention trials. Enzyme replacement therapy may stabilize kidney function. However, its long-term effect on kidney survival is not known. Moreover, there is no early known predictor of kidney dysfunction to adjust and evaluate effectiveness of enzyme replacement therapy. Our studies of renal GL-3 clearance comparing pre-and post-ERT renal biopsies using the above methods will allow us to determine whether age at institution of treatment and ERT dose affect ERT induced GL-3 cellular clearance, especially from those cells where ERT is less effective, i.e., podocytes, vascular smooth muscle cells and distal tubular cells. Finally, it is our hypothesis that mosaicism in Fabry disease females is such that cells such as podocytes are either affected or normal and that ERT clearance in the affected podocytes in females will, as in males, be dependant on age of institution of treatment and ERT dose.
- Conditions
- Fabry Disease
- Keywords
- Fabry disease, kidney function, kidney structure morphometry, Fabry kidney disease, Podocytes
- Medical subject headings
- Fabry Disease
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
The secondary endpoint for the determinants of renal structural responses to ERT will be GL-3 reduction from baseline to 5, 11 and 60 months in a composite of structural parameters which will be determined in our natural history studies.
Measured: Baseline, 5, 11 and 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2012 (estimated)
- Study startOct 2010
- Primary completion31 Jul 2030 (estimated)
- Study completion31 Jul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fabry DiseaseStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- Rare Diseases Clinical Research Network, National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Washington University School of Medicine, Haukeland University Hospital
- Responsible party
- Sponsor
- Investigators
- Chet Whitley, MD, Principal investigator, University of MinnesotaMichael Mauer, MD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01581424
- Sponsor's protocol ID
- 100349
- Other IDs
- U54NS065768
- Acronym
- LDN6702
- Status last verified
- Aug 2026
- First submitted
- 17 Jan 2012
- Last updated
- 14 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natural History and Structural Functional Relationships in Fabry Renal Disease Natural History, Structural Functional Relationships and Determinants of Renal Structural Responses (Changes) With Enzyme Replacement Therapy in Fabry Disease
- ClinicalTrials.gov ID
- NCT01581424
- Acronym / sponsor ID
- LDN6702 / 100349
- Conditions
- Fabry Disease
- Keywords
- Fabry disease, kidney function, kidney structure morphometry, Fabry kidney disease, Podocytes
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Collaborators
- Rare Diseases Clinical Research Network, National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Washington University School of Medicine, Haukeland University Hospital
- Study start
- Oct 2010
- Primary completion
- 31 Jul 2030 (estimated)
- Study completion
- 31 Jul 2030 (estimated)
- First posted
- 20 Apr 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Much of the natural history of Fabry renal structural changes will occur without detectable renal functional alterations.
- 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.
- 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.
The second component examines the effects of age and gender at start of enzyme replacement therapy (ERT), as well as dosage levels of ERT on the renal cellular clearance of GL3 from Fabry patients by comparing baseline to follow-up kidney biopsies performed 5, 11, and 60 months later, with all comparisons matched for ERT treatment duration. Our hypotheses for this component of the study are as follows:
- 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.
- 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.
- 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.
- Affected cells will be cleared of GL-3 equivalently in females and males.
Detailed description
Fabry disease is a rare genetic disease with deficient activity of enzyme alpha-galactosidase A. Deficient activity of this enzyme leads to the accumulation of lipid-derived inclusions in different organs including kidney, heart and vessels. These inclusions can be found in the kidney even before birth. The earliest known clinical manifestation of Fabry kidney disease is the appearance of excess protein in the urine, which usually occurs in the second decade of life. However, our studies, as well as those of other investigators show evidence that kidney injury starts much earlier. Once excess protein is found in the urine, kidney function deterioration becomes progressive, and most Fabry patients require kidney transplantation or hemodialysis in the third to fifth decade of life. The lesion or composite of lesions responsible for functional deterioration of the kidney in Fabry disease are not well known. Their delineation using quantitative, unbiased, morphometric methods will help to understand this disease, and to develop surrogate structural outcomes for early intervention trials. Enzyme replacement therapy may stabilize kidney function. However, its long-term effect on kidney survival is not known. Moreover, there is no early known predictor of kidney dysfunction to adjust and evaluate effectiveness of enzyme replacement therapy. Our studies of renal GL-3 clearance comparing pre-and post-ERT renal biopsies using the above methods will allow us to determine whether age at institution of treatment and ERT dose affect ERT induced GL-3 cellular clearance, especially from those cells where ERT is less effective, i.e., podocytes, vascular smooth muscle cells and distal tubular cells. Finally, it is our hypothesis that mosaicism in Fabry disease females is such that cells such as podocytes are either affected or normal and that ERT clearance in the affected podocytes in females will, as in males, be dependant on age of institution of treatment and ERT dose.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 1 year to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- Patients with serum creatinine more than 2.5 mg/dL or known to have a renal disease other than Fabry.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Natural History and Determinants of Renal Structural Responses (Changes) to Enzyme Replacement Therapy in Fabry Disease
Time frame: Natural history component, cross sectional; ERT component, 5, 11, and 60 months
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.
1 secondary outcome
Natural History and Determinants of Renal Structural Responses (Changes) to Enzyme Replacement Therapy in Fabry Disease
Time frame: Baseline, 5, 11 and 60 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Chet Whitley, MD principal investigator
University of Minnesota
Michael Mauer, MD principal investigator
University of Minnesota
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Fabry Disease, run by University of Minnesota at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Michael Mauer, MD (612-626-2720, mauer002@umn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Natural History and Determinants of Renal Structural Responses (Changes) to Enzyme Replacement Therapy in Fabry Disease (time frame: Natural history component, cross sectional; ERT component, 5, 11, and 60 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2026.