Renal Protective Effect of ACEI and ARB in Primary Hyperoxaluria

NCT00280215 | Withdrawn Phase 3

• 2 other identifiers: 2203-05NIH grant # DK 73354
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will test the effectiveness of two medications: ACEI (angiotensin converting enzyme inhibitor)and ARB (angiotensin receptor blocker) in reducing the renal injury induced by hyperoxaluria in patients with Primary Hyperoxaluria. Hypothesis: Calcium oxalate crystal deposition in the kidney causes inflammation and resulting injury to kidney tissue. Angiotensin blockade will improve these changes, thus slowing the progression of renal insufficiency in patients with Primary Hyperoxaluria.

Conditions

Hyperoxaluria

Keywords

Primary Hyperoxaluria

Outcome Measures

Primary Outcomes (1)

• Two-year change in the urinary markers of renal tubular injury and interstitial fibrosis

  2 years

Secondary Outcomes (1)

• Rate of change in 1. Renal tubular injury markers and 2. Renal function as determined by serum creatinine and creatinine clearance.

  2 years

Study Arms (2)

1

ACTIVE COMPARATOR

Patients will be randomized to a combination of Angiotensin Converting Enzyme Inhibitor and Angiotensin Receptor Blocker. Patients will be randomized to a combination of ARB(losartan 50 mg daily in adult patients, 0.7 mg/kg/day in patients \< 40 kg) ACE-I (lisinopril 10 mg daily in adult patients, 0.15 mg/kg/day in pediatric patients \< 40 kg) to be taken for 24 months.

Drug: ACEI / Angiotensin converting enzyme inhibitor; Drug: ARB /Angiotensin Receptor Blocker

2

PLACEBO COMPARATOR

Patients will take placebo for 24 months.

Drug: Placebo

Interventions

ACEI / Angiotensin converting enzyme inhibitor DRUG

Patients will be randomized to a combination of Angiotensin Converting Enzyme Inhibitor and Angiotensin Receptor Blocker, Patients will be randomized to a combination of ARB(losartan 50 mg daily in adult patients, 0.7 mg/kg/day in patients \< 40 kg) ACE-I (lisinopril 10 mg daily in adult patients, 0.15 mg/kg/day in pediatric patients \< 40 kg) to be taken for 24 months.

Also known as: Lisinopril

1

ARB /Angiotensin Receptor Blocker DRUG

Patients will be randomized to a combination of Angiotensin Converting Enzyme Inhibitor and Angiotensin Receptor Blocker,Patients will be randomized to a combination of ARB(losartan 50 mg daily in adult patients, 0.7 mg/kg/day in patients \< 40 kg) ACE-I (lisinopril 10 mg daily in adult patients, 0.15 mg/kg/day in pediatric patients \< 40 kg) to be taken for 24 months.

Also known as: Losartan

1

Placebo DRUG

Patients will receive placebo for 24 months

2

Eligibility Criteria

• Age: 10 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of PH established by liver enzyme analysis in the patient or an affected sibling, DNA testing for mutations of the AGXT and GR/HPR gene, or meeting clinical criteria (Urine oxalate \> 70 mg/1.73 m2/day in the absence of malabsorption or dietary excess of oxalate. Elevated urine glycolate or glycerate provides supporting evidence of type I or type II PH, respectively).
• Hyperoxaluria that persists during treatment with pyridoxine.
• Ten years of age or older.
• Glomerular filtration rate \> 50 ml/min/1.73 m2 at the start of the study.
• Women of child bearing age will be required to use adequate contraception for 3 months before and throughout the study.
• Patients will be on a stable program of pyridoxine, neutral phosphate, or citrate medications -

You may not qualify if:

• a. Age \< 10 years. b. Glomerular filtration rate \< 50 at start of study c. Hypersensitivity to ACEI or ARB medications d. Chronic use of ACEI or ARB medications prior to enrollment e. Hyperkalemia f. Previous renal transplant g. Homozygosity for the G170R mutation of AGXT h. Unwillingness to use adequate contraception during the study. i. Pregnancy

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Related Publications (28)

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  BACKGROUND

Related Links

• Mayo Clinic Hyperoxaluria Center home page
• The Oxalosis and Hyperoxaluria Foundation
• Mayo Clinic Hyperoxaluria Center-disease information page

MeSH Terms

Conditions

Hyperoxaluria; Hyperoxaluria, Primary

Interventions

Angiotensin-Converting Enzyme Inhibitors; Lisinopril; Angiotensin Receptor Antagonists; Losartan

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Study Officials

• Dawn S Milliner, M.D.

  Mayo Clinic Hyperoxaluria Center, Rochester MN

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 19, 2006
• First Posted: January 20, 2006
• Study Start: December 1, 2007
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: April 7, 2015

Record last verified: 2015-04