Study to Observe Disease Progession In Alport Syndrome Patients
Research type
Research Study
Full title
A Natural History Study to Observe Disease Progression, Standard of Care and Investigate Biomarkers in Alport Syndrome Patients
IRAS ID
164690
Contact name
Neil Turner
Contact email
Sponsor organisation
Regulus Therapeutics
Duration of Study in the UK
2 years, 9 months, 12 days
Research summary
Alport syndrome is an inherited form of kidney disease caused by mutations in genes coding for the capillary basement membrane collagen IV. The prevalence of mutations in the collagen IV family of genes is estimated to be 1 in 5,000 individuals. Multiple mutations have been identified in each of 3 distinct collagen IV alpha genes. Each chain is a key component of the collagen IV network, which is critical for maintaining the structure and integrity of the glomerular basement membrane. Alport syndrome is characterized by progressive glomerulonephritis, leading to glomerulosclerosis, tubulo-interstitial disease and organ failure.
Regardless of the category of mutation, patients with Alport syndrome all progress, and eventually develop end-stage renal disease (ESRD), requiring dialysis or renal transplantation.
Although renal transplantation has been shown to increase the survival of patients with Alport syndrome, it is associated with significant morbidity, even if successful in preventing death. In the U.S. there are no approved agents to delay time to ESRD for patients with Alport syndrome. Numerous agents have been investigated for their ability to reduce proteinuria and improve other symptoms associated with Alport syndrome. These agents include cyclosporine, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II type I receptor blockers (ARBs) and mineralocorticoid receptor antagonists. Only ACE inhibitors have been shown to reduce the time to dialysis in treated patients as compared to family relatives with Alport syndrome
who were not receiving ACE inhibitors.Thus an urgent need remains for the development of new therapeutics that can reduce the degree of fibrosis and renal inflammation, improve renal function and delay the time to dialysis for patients with Alport syndrome.
The study will collect data to characterize the progression of renal dysfunction in Alport syndrome patients.
The sequential sampling of subjects' urine and/or blood will allow an assessment of the rate of change of established clinical endpoints, such as GFR and/or the rate of change of other renal biomarkers (proteinuria and β-2 microglobulin) in subjects whose renal function is steadily declining.
The identification of surrogate markers that track the decline of renal function and could correlate with time to end-stage renal disease (ESRD) is a key goal of the natural history study.
REC name
West Midlands - Black Country Research Ethics Committee
REC reference
15/WM/0010
Date of REC Opinion
24 Feb 2015
REC opinion
Further Information Favourable Opinion