Renal Protective Effect of ACEI and ARB in Primary Hyperoxaluria
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Hyperoxaluria |
Drug: ACEI / Angiotensin converting enzyme inhibitor Drug: ARB /Angiotensin Receptor Blocker Drug: Placebo |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Prevention |
| Official Title: | Renal Protective Effect of ACEI and ARB in Primary Hyperoxaluria |
- Two-year change in the urinary markers of renal tubular injury and interstitial fibrosis [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Rate of change in 1. Renal tubular injury markers and 2. Renal function as determined by serum creatinine and creatinine clearance. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 40 |
| Study Start Date: | December 2007 |
| Estimated Study Completion Date: | December 2011 |
| Estimated Primary Completion Date: | December 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: 1
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
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.
Other Name: Lisinopril
Drug: ARB /Angiotensin Receptor Blocker
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.
Other Name: Losartan
|
|
Placebo Comparator: 2
Patients will take placebo for 24 months.
|
Drug: Placebo
Patients will receive placebo for 24 months
|
Detailed Description:
In patients with primary hyperoxaluria (PH), deficiency of hepatic enzymes important in disposition of glyoxylate results in marked hyperoxaluria. Calcium oxalate crystals and high oxalate concentrations in the renal filtrate result in inflammation and injury in the renal parenchyma. Loss of renal function over time is characteristic, with end stage renal failure occurring in half the patients by age 35 years, but as early as infancy in some patients. Experience in animal models of hyperoxaluria, and from other renal diseases, supports a role for ACEI and ARB medications in ameliorating inflammation and injury thus providing a renal protective effect.
We propose to study the short-term effect of combined angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocking (ARB) therapy in patients with PH, in a controlled, randomized, two-year study. Primary endpoints will be urinary markers of renal tubular injury (retinol binding protein (RBP), alpha 1 microglobulin (α1m), γ-glutamyl transferase (GGT)) and interstitial fibrosis (transforming growth factor beta 1 (TGFβ1). Secondary endpoints will be the rates of change in renal tubular injury and renal function as determined by serum creatinine and creatinine clearance.
Eligibility| Ages Eligible for Study: | 10 Years to 80 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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 -
Exclusion Criteria:
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
-
Contacts and Locations More Information
Additional Information:
Publications:
| Responsible Party: | Dr. Dawn S. Milliner, Mayo Clinic, Rochester MN |
| ClinicalTrials.gov Identifier: | NCT00280215 History of Changes |
| Other Study ID Numbers: | 2203-05, NIH grant # DK 73354 |
| Study First Received: | January 19, 2006 |
| Last Updated: | July 8, 2010 |
| Health Authority: | United States: Federal Government |
Keywords provided by Mayo Clinic:
|
Primary Hyperoxaluria |
Additional relevant MeSH terms:
|
Hyperoxaluria Hyperoxaluria, Primary Kidney Diseases Urologic Diseases Carbohydrate Metabolism, Inborn Errors Metabolism, Inborn Errors Genetic Diseases, Inborn Metabolic Diseases Angiotensin-Converting Enzyme Inhibitors Lisinopril Enzyme Inhibitors Losartan |
Angiotensin Receptor Antagonists Protease Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antihypertensive Agents Cardiovascular Agents Therapeutic Uses Cardiotonic Agents Protective Agents Physiological Effects of Drugs Anti-Arrhythmia Agents Angiotensin II Type 1 Receptor Blockers |
ClinicalTrials.gov processed this record on May 22, 2013