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Trial record 13 of 13 for:    "primary hyperoxaluria"

Hydroxyproline Influence on Oxalate Metabolism

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Mayo Clinic
Sponsor:
Collaborators:
Rare Diseases Clinical Research Network
Information provided by (Responsible Party):
Dawn S. Milliner, M.D., Mayo Clinic
ClinicalTrials.gov Identifier:
NCT02038543
First received: December 19, 2013
Last updated: September 16, 2014
Last verified: September 2014
  Purpose

Primary hyperoxaluria is an inborn error of metabolism that results in marked overproduction of oxalate by the liver. The excess oxalate causes kidney failure and can cause severe systemic disease due to oxalate deposition in multiple body tissues.

Metabolic pathways that lead to oxalate are poorly understood, but recent evidence suggests that hydroxyproline may play a role. Sources of hydroxyproline include the diet and bone turnover. If hydroxyproline can be confirmed as a signficant factor in primary hyperoxaluria, diet modification might be of value in reducing the severity of disease.

This protocol, in which hydroxyproline labelled with a cold isotope is infused intravenously in patients with primary hyperoxaluria, will allow us to measure the amount of oxalate produced from hydroxyproline. The contribution of hydroxyproline metabolism to the amount of oxalate excreted in urine in will be able to be determined for patients with each of the known types of primary hyperoxaluria.


Condition Intervention Phase
Hyperoxaluria
Drug: Hydroxyproline and Leucine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Influence of Hydroxyproline Plasma Concentration on Its Metabolism to Oxalate

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • The mean percent conversion of hydroxyproline to urinary oxalate [ Time Frame: Participants will be followed for the duration of study infusion and observation, an average of 24 hours. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The mean percent conversion of hydroxyproline to urinary glycolate [ Time Frame: Participants will be followed for the duration of the study infusion and observations, an average of 24 hours. ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: September 2013
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Primary hyperoxaluria patients
Subjects will be infused with 13C5-hydroxyproline and 2H3-leucine for 6 hrs in the CRU. The metabolic flux of 2H3-leucine has been well characterized, and is used as a control when studying the metabolism of trace infusions of labeled amino acids 3. Blood samples will be obtained every 30 min to determine the enrichment of plasma with 13C5-hydroxyproline and 2H3-leucine. Urine collections will be obtained hourly. The fluxes of whole body hydroxyproline and leucine will be calculated
Drug: Hydroxyproline and Leucine
Subjects will be infused with 13C5-hydroxyproline and 2H3-leucine for 6 hrs in the CRU. The metabolic flux of 2H3-leucine has been well characterized, and is used as a control when studying the metabolism of trace infusions of labeled amino acids 3. Blood samples will be obtained every 30 min to determine the enrichment of plasma with 13C5-hydroxyproline and 2H3-leucine. Urine collections will be obtained hourly. The fluxes of whole body hydroxyproline and leucine will be calculated
Other Names:
  • 13C5-hydroxyproline
  • 2H3-leucine

Detailed Description:

The purpose of this study is to determine the contribution of hydroxyproline metabolism to urinary oxalate and glycolate excretion in patients with primary hyperoxaluria.

Oxalic acid (COOH)2 is an end product of metabolism that is synthesized mainly in the liver. We have estimated that 10 - 20 mg is synthesized in the body of healthy adults each day (1). The main precursor of oxalate is glyoxylate (CHO•COOH). The bulk of the glyoxylate formed is normally transaminated to glycine (NH2•CH2•COOH) by alanine: lyoxylate aminotransferase (AGT) or reduced to glycolate (CHOH•COOH) by glyoxylate reductase (GR). Less than 10% of the glyoxylate is oxidized to oxalate by lactate dehydrogenase (LDH). In individuals with the disease, primary hyperoxaluria, AGT, GR, or HOGA enzyme is deficient and the amount of oxalate synthesized by the liver increases to 80 - 300 mg per day. The increased oxalate excreted in urine can cause damage to kidney tissue. Calcium oxalate stones may form in the kidney or calcium oxalate crystals may deposit in renal tubules and the renal parenchyma (nephrocalcinosis). An increased rate of oxalate synthesis could also contribute to idiopathic calcium oxalate stone disease. Understanding the pathways of endogenous oxalate synthesis and identifying strategies that decrease oxalate production could be beneficial for individuals with these diseases.

Hydroxyproline is the primary source of glyoxylate identified in the body (2). Daily collagen turnover of bone results in the formation of 300 - 450 mg of hydroxyproline, which cannot be re-utilized by the body and is broken down. This metabolism yields 180 - 250 mg of glyoxylate. Further hydroxyproline is obtained from the diet, primarily from meat and gelatin-containing products. The bulk of the glyoxylate formed is converted to glycine by the liver enzyme AGT, some to glycolate and a small amount to oxalate. The proportion of these metabolites is not known with any certainty. In this study, a quantitative estimate of the metabolites formed will provide estimates of the contribution of hydroxyproline turnover to daily oxalate production. These experiments will provide valuable information for the future assessment of the contribution of hydroxyproline metabolism to oxalate production in individuals with primary hyperoxaluria.

  Eligibility

Ages Eligible for Study:   15 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Confirmed diagnosis of primary hyperoxaluria
  • eGFR (by serum creatinine) > 50ml/min/1.73m2

Exclusion criteria:

  • eGFR < 50 ml/min/1.73m2
  • History of liver or kidney transplant
  • Primary hyperoxaluria patients who have responded to pyridoxine therapy with reduction of urine oxalate excretion to < 0.45 mmol/1.73m2/day.
  • Pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02038543

Contacts
Contact: Julie B Olson, RN 800-270-4637 hyperoxlauriacenter@mayo.edu
Contact: Barb M Seide 800-270-4637 hyperoxlauriacenter@mayo.edu

Locations
United States, Minnesota
Mayo Clinic Hyperoxaluria Center Recruiting
Rochester, Minnesota, United States, 55905
Contact: Julie B Olson, RN    800-270-4637    hyperoxaluriacenter@mayo.edu   
Sponsors and Collaborators
Mayo Clinic
Rare Diseases Clinical Research Network
Investigators
Principal Investigator: Dawn Milliner, MD Mayo Clinic
Principal Investigator: Dawn S Milliner, MD Mayo Clinic Hyperoxaluria Center/ Rare Kidney Stone Consortium
  More Information

No publications provided

Responsible Party: Dawn S. Milliner, M.D., Rare Kidney Stone Consortium Director, Mayo Clinic
ClinicalTrials.gov Identifier: NCT02038543     History of Changes
Other Study ID Numbers: 13-000150, U54DK083908
Study First Received: December 19, 2013
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
Hyperoxaluria
Oxalate
Primary Hyperoxaluria
PH

ClinicalTrials.gov processed this record on November 20, 2014