Clinical Trial: Multi-center Controlled Clinical Trials in Alport Syndrome-A Feasibility Study

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Observational

Official Title: Multi-center Controlled Clinical Trials in Alport Syndrome-A Feasibility Study

Brief Summary: Over the past 30 years much has been learned about the molecular genetics and natural history of familial forms of hematuria. However, enhanced understanding of these conditions has yet to generate effective therapies for Alport syndrome(AS), the form of familial hematuria associated with end-stage renal disease. Males with AS inevitably develop end-stage kidney failure, with a 50% likelihood of dialysis or kidney transplantation by age 25 years. There is no proven treatment for AS, although studies in animals have suggested several promising potential therapies. Pharmacological or biological treatments that might delay or prevent the development of kidney failure exist, but need to be evaluated through clinical trials. Researchers interested in implementing clinical trials in AS will face several challenges, the foremost of which is the relative rarity of the disease, necessitating aggressive efforts to identify and recruit potential subjects for multi-center collaborative clinical trials. The Alport Syndrome Research Collaborative (ARC) was established in 2009 as a partnership of the Alport Syndrome Treatments and Outcomes Registry (ASTOR), the European Alport Registry and centers of AS research in Canada, China and France with the objective of testing potential treatments to delay or prevent terminal renal failure in people with AS. In this feasibility study the five ARC centers will interrogate existing AS registries and databases, and monitor accrual of new AS cases over an 18-month period, in order to quantify subjects in the disease categories of interest. As part of this project we will examine the utility of urinary uromodulin excretion as a marker of kidney injury and potential trial endpoint in AS clinical trials. Our goals are to (1) demonstrate that participating centers have access to sufficient numbers of males and females with AS to populate adequately-powered clinical trials focused on two clinical targets, microalbuminuria and overt proteinuria, an

Detailed Summary:

The specific aims of this multi-site study are two-fold. The first aim is to demonstrate that the Alport syndrome (AS) populations available to us through our registries and clinical networks include sufficient numbers of affected subjects in the early stages of the AS nephropathy to reach specific recruitment targets. The clinical populations thus identified will form the basis of a future RO1 proposal for funding of a clinical trial. The second aim is to examine urinary uromodulin excretion and its relationship to urinary albumin excretion in early AS, to assess the utility of urinary uromodulin as a marker of renal tubular injury in AS

Specific Aim #1:

Five regional recruitment centers in the United States, Canada, China, France and Germany will interrogate existing AS registries and databases, and monitor accrual of new AS cases over an 18-month period, in order to quantify subjects in four disease categories:

  • Normal albumin excretion (albumin/creatinine ratio [ACR] < 30 mg/g), on no treatment
  • Microalbuminuria (ACR > 30 mg/g, protein/creatinine ratio [Prot/Cr] < 0.2 mg/mg), on no treatment
  • Overt proteinuria (Prot/Cr > 0. 2 mg/mg), on no treatment
  • Overt proteinuria (Prot/Cr > 0.2 mg/mg), despite treatment with an angiotensin converting enzyme inhibitor

Regional Centers *

  • United States: Alport Syndrome Treatments and Outcomes Registry (ASTOR), a collaborative effort of University of Minnesota and University of Utah
  • Canada: University of Toronto and The
    Sponsor: University of Minnesota - Clinical and Translational Science Institute

    Current Primary Outcome: Multi-center Controlled Clinical Trials in Alport Syndrome-A Feasibility Study [ Time Frame: 2 years ]

    The primary outcome to be measured is the number of subjects with Alport syndrome who would meet eligibility criteria for an anticipated clinical treatment trial. Power calculations indicate that the trial would require recruitment of 90 total subjects, stratified into 4 groups based on urine albumin and protein excretion.


    Original Primary Outcome: Same as current

    Current Secondary Outcome: Multi-center Controlled Clinical Trials in Alport Syndrome-A Feasibility Study [ Time Frame: 2 years ]

    The primary outcome to be measured is the differences in urinary uromodulin excretion in Alport subjects stratified by urinary albumin excretion.


    Original Secondary Outcome: Same as current

    Information By: University of Minnesota - Clinical and Translational Science Institute

    Dates:
    Date Received: September 20, 2012
    Date Started: September 2012
    Date Completion: December 2017
    Last Updated: April 19, 2017
    Last Verified: April 2017