Clinical Trial: Proteomics of Primary Hyperoxaluria Type 1

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Observational

Official Title: "Pilot Study: Proteomics of Primary Hyperoxaluria Type 1 (PH1): A Rare Calcium Oxalate Stone Disease"

Brief Summary: The purpose of this study is to identify unique urine protein markers of Primary Hyperoxaluria type 1 (PH1) compared to healthy controls. Urine protein markers can be identified by "proteomic" analyses in which proteins are processed in a lab to break them down into smaller building blocks. Using analytical chemistry techniques and specialized equipment many proteins can be identified and measured. Most proteins are found in healthy living cells while subtle changes in these proteins or the presence of different markers reflect abnormal processes and patterns of disease. When identified in disease, protein biomarkers can help to determine if a disease responds to new types of therapies. In this study, changes in urine proteomic patterns over time, their association with change in estimated (calculated) kidney filtering function, and the relative risk for progression of PH1 will be determined. Additionally, as part of the study, the investigators will measure urinary proteins and peptides that are markers of kidney tissue protection (for healthy healing of the kidneys from ongoing damage from high urine oxalate levels, oxalate crystals and stones) to establish if and when these markers are prospectively decreased in PH1 urine. Longitudinal studies of urine "proteomics" may assist in identifying the mechanisms behind PH1-related progression of kidney failure and might contribute important information towards future identification and development of effective therapies to slow or prevent kidney failure in PH1.

Detailed Summary:

Primary hyperoxaluria type 1 (PH1) is a rare genetically inherited disorder seen in 1:100,000-150,000 people and is often underdiagnosed in children. PH1 is characterized by abnormally high levels of oxalate in the blood and urine, crystals in the urine, frequent formation of kidney stones, and hardening (calcification) of the kidneys called "nephrocalcinosis." Identification and evaluation of proteins and peptides (biomarkers) in the urine of PH1 patients may provide insight into the process of kidney damage that occurs over time in PH1 by evaluating these markers at some point after diagnosis and over long-term. By studying biomarker patterns in the urine of PH1 patients that are collected over the course of their disease, information about changes in biomarker patterns over time may provide important clues about those patients at a higher risk for faster progression to end stage kidney failure and may serve as important outcomes for new therapies in the future, too.

Primary study objective: Identify the unique urine proteomic markers of PH1 versus healthy intra-familial sibling controls of PHI patient specimens at one point in time (cross-sectionally).

Secondary study objective: Determine change over time in urine proteomic patterns, their association with change in estimated (calculated) kidney filtering function, and the relative risk for progression of PH1 and kidney disease progression.

Tertiary study objective: Establish if and when, in the course of PH1, the protective effects of the body (and kidneys) for normal kidney tissue healing are decreased/ lost as evidenced by the long-term change in biomarker patterns.

The primary endpoints of this study include standard clinical endpoints (data that a kidney do
Sponsor: Ann & Robert H Lurie Children's Hospital of Chicago

Current Primary Outcome: Phase 1: Urine proteomic markers. [ Time Frame: Baseline ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Phase 2: Urine proteomic marker patterns and their change over time related to progression of chronic kidney disease in primary hyperoxaluria type 1 (PH1). [ Time Frame: 5 years ]
  Quantitative Mass Spectrometry analyses of previously collected, archived, and de-identified serial urine specimens (collected in up to/more than 5 years of follow-up) from patients with Primary Hyperoxaluria type 1 (PH1) will be completed to determine if a change occurs in: (1) urine proteomic patterns (proteins and peptides) over time using previously collected data on: (a) estimated kidney filtering function declines (indicating kidney disease progression) and (b) oxalate concentrations in the urine (or plasma) continue to rise. Statistical analyses will determine the relationship between the urine protein/peptide pattern changes over time to kidney disease progression in PH1. All previously collected, de-identified, and archived data and urine specimens will be provided by Mayo Clinic (Rochester, MN).
• Phase 2: Establish by urine proteome pattern changes if & when normal healing processes of the kidneys are lost, which reflect progressive kidney damage. [ Time Frame: 5 years ]
  Establish if and when, in the 5 year serial follow-up of Primary Hyperoxaluria type 1 (PH1) urine specimens, normal kidney tissue healing is decreased/lost (down regulated) and pathologic kidney tissue damage increases (upregulated). This will be evidenced by the long-term change in biomarker patterns and progressive loss of kidney filtering function. This will be accomplished using: (1) standard identification of specific urine protein and peptides using known databases and (2) statistical analyses for urine protein/peptide marker pattern development reflective of kidney pro-injury and irreversible kidney cell damage. (All serially collected, de-identified, and archived urine specimens and data will have been provided by Mayo Clinic, Rochester, MN).

Original Secondary Outcome: Same as current

Information By: Ann & Robert H Lurie Children's Hospital of Chicago

Dates:
Date Received: February 9, 2017
Date Started: January 5, 2017
Date Completion: June 30, 2018
Last Updated: February 23, 2017
Last Verified: February 2017