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

This study has been completed.
Sponsor:
Information provided by:
Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier:
NCT00309257
First received: March 30, 2006
Last updated: October 5, 2009
Last verified: October 2009
  Purpose

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.


Condition Intervention Phase
Alport Syndrome
Drug: ACE I, ATA II and Statins
Drug: Benazepril, Valsartan and Fluvastatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of an Intensified Treatment With ACE-inhibitors, Angiotensin II Receptor Antagonists and Statins in Alport Syndrome

Resource links provided by NLM:


Further study details as provided by Mario Negri Institute for Pharmacological Research:

Primary Outcome Measures:
  • Urinary protein excretion [ Time Frame: At baseline and monthly ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Blood pressure [ Time Frame: At baseline, monthly and when deemed clinically appropriate ] [ Designated as safety issue: No ]
  • Urinary podocyte excretion [ Time Frame: At baseline and every six months. ] [ Designated as safety issue: No ]

Enrollment: 9
Study Start Date: January 2004
Study Completion Date: October 2009
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ACE inhibitor, ATA II antagonists and Statins Drug: ACE I, ATA II and Statins Drug: Benazepril, Valsartan and Fluvastatin

Patients will be given a low dose of Benazepril, 10 mg/die,that, if tolerated, will be up-titrated, after a week,to 20 mg/day.

Patients will be given Valsartan, 80 mg/die,up-titrated after a week to 160 mg/die. Fluvastatin will be started at 40 mg/die.If tolerated, will up-titrated to 80 mg/die. In case of liver, muscular or renal toxicity, fluvastatin will be back-titrated to 40 mg or withdrawn as deemed appropriate.


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   15 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age ≥15 years
  • Alport disease
  • Creatinine clearance >20 ml/min/1.73 mq with variation of less than 30% in the three months prior to study entry
  • written informed consent. For patients <18 years old a written informed consent of both parents is needed

Exclusion Criteria:

  • treatment with immunosuppressive drugs in the six months preceding the study
  • vascular disease of the kidney
  • obstructive uropathy, prostatic hypertrophy, incomplete bladder emptying
  • transplanted kidney
  • clinically relevant electrolyte imbalance (e.g., hyperkaliemia with serum K+ > 5.5 mEq/l)
  • any concomitant medication with drugs that may directly affect UAE including ACE-inhibitors, angiotensin II receptor antagonists, non dihydropyridine CCBS, HMGCoA reductase inhibitors in the last one month
  • history of hypersensitivity to the study drugs
  • impossibility to temporary withdrawn ACE-I or ATA II or statins (heart failure, cardiovascular events over the last three months)
  • any clinically relevant condition that may affect study participation and/or study results
  • pregnancy, ineffective contraception, breast feeding
  • inability to fully understand the purposes/risks of the study and/or to provide a written informed consent
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00309257

Locations
Italy
Clinical Research Center for Rare Diseases
Ranica, Bergamo, Italy, 24020
Sponsors and Collaborators
Mario Negri Institute for Pharmacological Research
Investigators
Principal Investigator: Erica Daina, MD Mario Negri Institute for Phrmacological Research
  More Information

No publications provided

Responsible Party: Mario Negri Institute for Pharmacological Research, Clinical Research Center for Rare Diseases Aldo and Cele Daccò
ClinicalTrials.gov Identifier: NCT00309257     History of Changes
Other Study ID Numbers: FVA01
Study First Received: March 30, 2006
Last Updated: October 5, 2009
Health Authority: Italy: Ministry of Health

Additional relevant MeSH terms:
Nephritis, Hereditary
Syndrome
Collagen Diseases
Congenital Abnormalities
Connective Tissue Diseases
Disease
Kidney Diseases
Nephritis
Pathologic Processes
Urogenital Abnormalities
Urologic Diseases
Angiotensin-Converting Enzyme Inhibitors
Benazepril
Fluvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Valsartan
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Anticholesteremic Agents
Antihypertensive Agents
Antimetabolites
Cardiovascular Agents
Enzyme Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014