Descriptive Analysis of Gut Microbiome Alterations in Hyperoxaluric Patients

To characterize the microbiome in 4 groups of subjects (primary hyperoxaluria type I (PH1), idiopathic CaOx stone, enteric hyperoxaluria (EH) and healthy participants) by comparing the number of species and diversity of the microbial populations and pathway for oxalate metabolism by paralleling the gene expression of enzymes involved in oxalate degradation by gut bacteria.

Study Overview

• Status: Unknown
• Conditions: Oxalate, Primary Hyperoxaluria, Microbiome

Detailed Description

Kidney stones affect as much as 10% of the US population with the most common type of stones made of calcium oxalate. Calcium and oxalate are present in the urine and can bind to each other, and form calcium oxalate kidney stones. Oxalate is absorbed in the gut from the food that is eaten and is removed from the body through urination. Gut bacteria is thought to play a role in decreasing oxalate absorption in the gut and its levels in the urine. With this research we hope to learn about differences in the bacteria that live in the gut of different groups of participants who are likely to form kidney stones, as well as healthy individuals. We will study healthy people with no history of kidney stones, people with a history of calcium oxalate (CaOx) kidney stones, people with a genetic disease called primary hyperoxaluria type1 (PH1) that increases their chances to form calcium oxalate kidney stones and, people with enteric hyperoxaluria (EH) a disease in which individuals have short bowels due to surgery which lead them to get calcium oxalate kidney stones.

Our research questions are:

1. How different is the gut bacteria between participants with the conditions that make them more likely to form kidney stones and healthy participants with no history of kidney stones?
2. Is there any difference in the function of the individual bacteria, Oxalobacter formigenes known to reduce oxalate, between healthy participants with no history kidney stones and participants with PH1?

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

• Study Contact: Name: Lama Nazzal, MD; Phone Number: 3877 212-686-7500; Email: lama.nazzal@nyumc.org
• Study Contact Backup: Name: Jessica Baylor, BA; Phone Number: 646-501-4159; Email: jessica.baylor@nyumc.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • New York University School of Medicine
      • Contact: Lama Nazzal, MD; Email: lama.nazzal@nyumc.org
      • Contact: Jessica Baylor, BA; Email: jessica.baylor@nyumc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

This is a cross sectional study with 60 patients that will collect 2 fecal samples within one week. We will include:

• 15 participants with healthy kidney function
• 15 participants with Calcium Oxalate kidney stone(s)
• 15 participants with Primary Hyperoxaluria type I
• 15 participants with Enteric Hyperoxaluria

Description

Inclusion Criteria:

• Primary hyperoxaluria: Patients diagnosed with type I PH by genetic testing and part of the Rare Kidney Stone Consortium (RKSC) Primary hyperoxaluria registry
• Enteric hyperoxaluria: Patients with Roux-en-Y-gastric-bypass
• Idiopathic CaOx stone : History of passing or having surgically removed a calcium oxalate kidney stone within 5 years of recruitment
• Healthy participants with no history of kidney or bowel disease

Exclusion Criteria:

• History of kidney or liver transplant
• History of antibiotics use within 6 months of recruitment

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
healthy; Individuals without a history of kidney or bowel disease
primary hyperoxaluria; Patients diagnosed with type I PH by genetic testing
enteric hyperoxaluria; Patients with Roux-en-Y-gastric-bypass.
calcium oxalate stone formers; History of passing or having surgically removed a calcium oxalate kidney stone within 5 years of recruitment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in composition of the fecal microbiome as measured by 16S ribosomal ribonucleic acid (rRNA) sequencing and whole genome shotgun sequencing between the study groups.	Diversity and abundance of operational taxonomic units (OTUs) between different groups of subjects will be tested. Data from shotgun sequencing and degenerate quantitative polymerase chain reactions (qPCRs) will yield comparative expressions of the oxalate metabolism genes between the groups.	1 year

Collaborators and Investigators

• Sponsor: VA New York Harbor Healthcare System
• Collaborators: Mayo Clinic; New York University

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Anticipated): June 1, 2018
• Study Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: May 25, 2016
• First Submitted That Met QC Criteria: June 4, 2016
• First Posted (Estimate): June 9, 2016

Study Record Updates

• Last Update Posted (Actual): September 26, 2017
• Last Update Submitted That Met QC Criteria: September 23, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Hyperoxaluria; Hyperoxaluria, Primary
• Other Study ID Numbers: RKSC6416