Renal Protective Effect of ACEI and ARB in Primary Hyperoxaluria
NCT ID: NCT00280215
Last Updated: 2015-04-07
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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WITHDRAWN
PHASE3
INTERVENTIONAL
2007-12-31
2011-12-31
Brief Summary
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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.
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Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
TRIPLE
Study Groups
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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.
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.
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.
2
Patients will take placebo for 24 months.
Placebo
Patients will receive placebo for 24 months
Interventions
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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.
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.
Placebo
Patients will receive placebo for 24 months
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Hyperoxaluria that persists during treatment with pyridoxine.
3. Ten years of age or older.
4. Glomerular filtration rate \> 50 ml/min/1.73 m2 at the start of the study.
5. Women of child bearing age will be required to use adequate contraception for 3 months before and throughout the study.
6. Patients will be on a stable program of pyridoxine, neutral phosphate, or citrate medications -
Exclusion Criteria
\-
10 Years
80 Years
ALL
No
Sponsors
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
NIH
Mayo Clinic
OTHER
Responsible Party
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Mayo Clinic, Rochester MN
Principal Investigators
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Dawn S Milliner, M.D.
Role: PRINCIPAL_INVESTIGATOR
Mayo Clinic Hyperoxaluria Center, Rochester MN
References
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Milliner DS, Eickholt JT, Bergstralh EJ, Wilson DM, Smith LH. Results of long-term treatment with orthophosphate and pyridoxine in patients with primary hyperoxaluria. N Engl J Med. 1994 Dec 8;331(23):1553-8. doi: 10.1056/NEJM199412083312304.
Khan SR, Shevock PN, Hackett RL. Urinary enzymes and calcium oxalate urolithiasis. J Urol. 1989 Sep;142(3):846-9. doi: 10.1016/s0022-5347(17)38928-0.
Lieske JC, Monico CG, Holmes WS, Bergstralh EJ, Slezak JM, Rohlinger AL, Olson JB, Milliner DS. International registry for primary hyperoxaluria. Am J Nephrol. 2005 May-Jun;25(3):290-6. doi: 10.1159/000086360. Epub 2005 Jun 15.
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Abbate M, Zoja C, Rottoli D, Corna D, Tomasoni S, Remuzzi G. Proximal tubular cells promote fibrogenesis by TGF-beta1-mediated induction of peritubular myofibroblasts. Kidney Int. 2002 Jun;61(6):2066-77. doi: 10.1046/j.1523-1755.2002.00380.x.
Toblli JE, Ferder L, Stella I, Angerosa M, Inserra F. Protective role of enalapril for chronic tubulointerstitial lesions of hyperoxaluria. J Urol. 2001 Jul;166(1):275-80.
Toblli JE, Stella I, Angerosa M, Nyberg C, Ferder L, Inserra F: Transforming growth factor-b1 (TGF--b1) and collagen typ III in hyperoxaluric rats treated with enalapril. J Am Soc Nephrol 8:528A, 1997.
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Related Links
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The Oxalosis and Hyperoxaluria Foundation
Mayo Clinic Hyperoxaluria Center-disease information page
Other Identifiers
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NIH grant # DK 73354
Identifier Type: -
Identifier Source: secondary_id
2203-05
Identifier Type: -
Identifier Source: org_study_id
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