View clinical trials related to Nephritis, Hereditary.
Filter by:This is a Phase 1, open-label, multi-center study of the safety, pharmacodynamics, and pharmacokinetics of RG-012 administered to subjects with Alport syndrome.
This international, multi-center, Phase 2/3 trial will study the safety, tolerability, and efficacy of bardoxolone methyl in qualified patients with Alport syndrome. The Phase 2 portion of the trial will be open-label and enroll up to 30 patients. The Phase 3 portion of the trial will be double-blind, randomized, placebo-controlled and will enroll up to 180 patients.
There is limited published clinical data about the natural history of renal disease in Alport syndrome. The RG012-01 study will collect data to characterize the progression of renal dysfunction in Alport syndrome patients. Patients with a confirmed diagnosis of Alport syndrome who have qualifying GFR will be considered for enrollment. 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.
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, and (2) to test the hypothesis that in males with AS urinary uromodulin excretion decreases as albuminuria and proteinuria increase and that uromodulin offers an independent and insightful measure of renal fibrosis and response to therapy.
This is a phase III, multi-centre, randomised, placebo-controlled, patient and investigator-blind study in paediatric patients with early stages of Alport syndrome to assess the safety and efficacy of the ACEi ramipril in slowing disease progression. Alport syndrome stages that describe the extent of renal damage and loss of function are defined as: - 0 Microhaematuria without microalbuminuria (usually at birth) - I Microalbuminuria (30-300 mg albumin/gCrea) - II Proteinuria >300 mg albumin/gCrea - III > 25% decline of normal renal function (creatinine clearance) - IV End stage renal failure (ESRF) Eligible patients with Alport stages 0 and I will be randomly assigned at a 2:1 ratio to receive once daily ramipril or placebo. In addition, Alport stage II patients may be treated open Label. Eligible patients who, or whose parents/legal guardian refuse randomisation after eligibility is confirmed, and patients who have been treated with ramipril prior to the study, may be treated open-label with ramipril as per protocol. The total number of patients will not exceed 120, with the number of randomised patients not exceeding 60, and the number of patients treated open label from Day 1 of the study aimed to be approximately 60. Randomised patients whose disease progresses to the next disease level during the 3 year treatment period will be unblinded, and open label ramipril treatment will be initiated and continued, respectively, depending on prior treatment randomisation.
The goal of the Microalbuminuria in Untreated Boys with Alport Syndrome study is to gather information about critical clinical time points such as when patients with small amounts of protein (microalbuminuria) in their urine progress to larger amounts (overt proteinuria). Large amounts of protein in the urine is often an early sign of kidney disease. Information needs to be collected in boys who are not taking medications known as angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) in order to obtain accurate data about the length of time between the onset of microalbuminuria and the start of overt proteinuria. This new information will give physicians a better understanding of how to treat patients with Alport syndrome. The information we gather by conducting this study will aid in planning future clinical trials because the identification of time points in disease progression, such as microalbuminuria and overt proteinuria, could reduce the time necessary to show a clinical benefit of a new treatment option. The study has been approved by the University of Minnesota's Institutional Review Board.
Alport syndrome (AS) represents a form of progressive hereditary nephritis in which the genetic defect resides in the synthesis of one of several subunits of type IV collagen, the predominant constituent of basement membranes in renal glomeruli. Renal impairment occurs with time and severe renal failure with hypertension and uremia represent the end stage of the disease, even if a high variability in the rate of progression is described.Males are usually affected by a progressive form of the disease. Affected females with X-linked syndrome usually have a good prognosis with a mild renal impairment. The disease is also associated to a sensor neural deafness which can occur in approximately half of the patient affected and usually correlates with renal impairment. No definite treatment exists in order to delay the time of dialysis or a kidney transplant. Many studies showed that Angiotensin converting enzyme (ACE) inhibitors slow glomerular filtration rate (GFR) decline and limit progression to end stage renal disease (ERDS) and dialysis in several chronic nephropathies associated with proteinuria. The combination of ACE-I with Angiotensin II receptor antagonists may reduce proteinuria more effectively than the two drugs alone. Moreover the addition of statins may synergize the antiproteinuric effects of ACE-I and ATAII antagonists in experimental models of chronic renal diseases. The purpose of this study is to evaluate the effect of a standardized multimodal nephroprotection intervention (Remission Clinic) in Alport patients with renal involvement.