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

NCT00309257 | Completed Phase 2

• 1 other identifier: FVA01
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Alport Syndrome

Outcome Measures

Primary Outcomes (1)

• Urinary protein excretion

  At baseline and monthly

Secondary Outcomes (2)

• Blood pressure

  At baseline, monthly and when deemed clinically appropriate

• Urinary podocyte excretion

  At baseline and every six months.

Study Arms (1)

ACE inhibitor, ATA II antagonists and Statins

EXPERIMENTAL

Drug: ACE I, ATA II and Statins; Drug: Benazepril, Valsartan and Fluvastatin

Interventions

ACE I, ATA II and Statins DRUG

ACE inhibitor, ATA II antagonists and Statins

Benazepril, Valsartan and Fluvastatin DRUG

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.

ACE inhibitor, ATA II antagonists and Statins

Eligibility Criteria

• Age: 15 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead

Study Sites (1)

Clinical Research Center for Rare Diseases

Ranica, Bergamo, 24020, Italy

Location

MeSH Terms

Conditions

Nephritis, Hereditary

Interventions

Hydroxymethylglutaryl-CoA Reductase Inhibitors; benazepril; Valsartan; Fluvastatin

Condition Hierarchy (Ancestors)

Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Nephritis; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses; Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Erica Daina, MD

  Mario Negri Institute for Phrmacological Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2006
• First Posted: March 31, 2006
• Study Start: January 1, 2004
• Primary Completion: June 1, 2008
• Study Completion: October 1, 2009
• Last Updated: April 4, 2023

Record last verified: 2009-10

Locations

IT (1)