Clinical Trial: Effects of an Intensified Treatment With ACE-I,ATA II and Statins in Alport Syndrome

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Effects of an Intensified Treatment With ACE-inhibitors, Angiotensin II Receptor Antagonists and Statins in Alport Syndrome

Brief Summary:

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.


Detailed Summary:

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 glomeruli, eye, cochlea. From a genetical point of view, the disease is quite heterogeneous, since we have X-linked, autosomal recessive and autosomal dominant variants of the syndrome. In most cases (about 80%) the model of inheritance is X-linked and the affected patients are males. Here the mutation stays on X-chromosome in a gene codifying for alpha-5(IV). In about 15% of patients the inheritance is autosomal recessive, with a severe disease both in males and females. The involved genes here are located on chromosome 2 and codifying respectively for alpha-3(IV) and alpha-4(IV) chains. In a 5% the model of inheritance is autosomal dominant and here the deterioration of renal function usually occurs more slowly.

Clinical manifestations include microscopic hematuria as the first finding, which can also became gross hematuria (episodes during upper respiratory infections) or manifest as intermittent (heterozygous females). Another sign is proteinuria of various degrees. It may be from insignificant, described in heterozygous females, or a progressive proteinuria (recessive or X-linked disease). It is evident from clinical studies of Alport patients that a persistent massive proteinuria, inducing a progressive interstitial fibrosis, indicates a very poor prognosis. The presence of glomerular podocytes has been described in urinary sediments of patients with renal diseases, including AS and recent data suggest that podocyturia could act as a marker for estimating the severity of active glomerular injury and as a predictor of disease progression. Renal impairment occurs with time and severe renal failure with hypertension and uremia represent the end
Sponsor: Mario Negri Institute for Pharmacological Research

Current Primary Outcome: Urinary protein excretion [ Time Frame: At baseline and monthly ]

Original Primary Outcome: Urinary protein excretion

Current Secondary Outcome:

  • Blood pressure [ Time Frame: At baseline, monthly and when deemed clinically appropriate ]
  • Urinary podocyte excretion [ Time Frame: At baseline and every six months. ]


Original Secondary Outcome:

  • Blood pressure
  • Urinary podocyte excretion


Information By: Mario Negri Institute for Pharmacological Research

Dates:
Date Received: March 30, 2006
Date Started: January 2004
Date Completion:
Last Updated: October 5, 2009
Last Verified: October 2009