Gut Kidney Axis in Enteric Hyperoxaluria

Gut Kidney Axis in Enteric Hyperoxaluria: A Clinical Prospective Study of the Effects of the Microbiome on Urinary Oxalate in Participants With Enteric Hyperoxaluria Fed a Moderate Oxalate Diet

40 subjects with a confirmed diagnosis of IBD or >6 months post-RYGB with a diagnosed USD event or kidney stone on imaging within the past three years and 40 healthy controls will be administered a high oxalate diet on Days 0-3 and Days 21-24 with a washout period on Days 4-7 and will be administered 250mg sodium oxalate on Days 8-20, via prepared spinach, from Weil Cornell Medicine's Clinical and Translational Science Center. Subjects will partake in four stool collections, four 24-h urine collections, two blood collections, and four sets of colonic permeability testing.

Study Overview

• Status: Recruiting
• Conditions: Enteric Hyperoxaluria
• Intervention / Treatment: Other: Moderately High Oxalate (MOx) Diet

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lama Nazzal, MD; Phone Number: 212-263-2922; Email: Lama.Nazzal@nyulangone.org
• Study Contact Backup: Name: David Goldfarb, MD; Phone Number: 212-263-0744; Email: David.Goldfarb@nyulangone.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health
      • Principal Investigator: Lama Nazzal, MD
      • Contact: Lama Nazzal, MD; Email: Lama.Nazzal@nyulangone.org
      • Principal Investigator: David Goldfarb, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• Subjects > 18 years and < 80 years of age
• a confirmed diagnosis of IBD or > 6 months post- RYGB, with a diagnosis USD event (renal colic with spontaneous stone passage, emergency room visits, or urological interventions) or have kidney stone on imaging (CT, MRI, or US) in the previous three years.
• We will include all racial and ethnic groups, and both men and women.

In order to be eligible in this study as a healthy control, an individual must meet all of the following criteria:

• Subjects > 18 years and < 80 years of age
• Healthy controls with no chronic diseases, not on any chronic medications, no history of GI pathology, or urinary stone disease (USD).
• We will include all racial and ethnic groups, and both men and women.

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

• pregnant or nursing women and people with any medical, psychiatric, debilitating disease/disorder or social condition that, in the judgment of the investigator, would interfere with or serve as a contraindication to adherence to the study protocol, ability to give ICF or complete the protocol.
• subjects with total and partial colectomy.
• subjects who received oral, intramuscular, or intravenous antibiotics within three months before screening.
• Patients with perianal disease usually receive recurrent antibiotics and, therefore, will be excluded from the study.
• patients with an ongoing symptomatic IBD flare or a flare within the previous three months
• patients with estimated glomerular filtration rates (eGFR) < 60 ml/min/1.73 m2 calculated by the CKD-EPI equation measured anytime within the preceding year.

An individual who meets any of the following criteria will be excluded from participation in this study as a healthy control:

• pregnant or nursing women and people with any medical, psychiatric, debilitating disease/disorder or social condition that, in the judgment of the investigator, would interfere with or serve as a contraindication to adherence to the study protocol, ability to give ICF or complete the protocol.
• subjects with total and partial colectomy.
• subjects who received oral, intramuscular, or intravenous antibiotics within three months before screening.
• Patients with perianal disease usually receive recurrent antibiotics and, therefore, will be excluded from the study.
• patients with an ongoing symptomatic IBD flare or a flare within the previous three months
• patients with estimated glomerular filtration rates (eGFR) < 60 ml/min/1.73 m2 calculated by the CKD-EPI equation measured anytime within the preceding year.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Healthy Controls	Other: Moderately High Oxalate (MOx) Diet; Diets will contain 16% protein, 30% fat, and 54% carbohydrate, and are controlled in the amounts of calcium (400mg), oxalate (250mg), ascorbic acid (50mg), fiber (30 grams) and, other nutrients. Each controlled diet will be consumed for four days. On days of controlled diets, subjects will be provided with 2 liters of bottled water per day to ensure adequate hydration. After the controlled diet period, there will be a three-day washout period, where participants will consume Ad-lib diets supplemented with a daily intake of oxalate in the form of cooked spinach to be taken with breakfast daily for a total of 2 weeks.
Experimental: Enteric Hyperoxaluria	Other: Moderately High Oxalate (MOx) Diet; Diets will contain 16% protein, 30% fat, and 54% carbohydrate, and are controlled in the amounts of calcium (400mg), oxalate (250mg), ascorbic acid (50mg), fiber (30 grams) and, other nutrients. Each controlled diet will be consumed for four days. On days of controlled diets, subjects will be provided with 2 liters of bottled water per day to ensure adequate hydration. After the controlled diet period, there will be a three-day washout period, where participants will consume Ad-lib diets supplemented with a daily intake of oxalate in the form of cooked spinach to be taken with breakfast daily for a total of 2 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary Oxalate Levels (UOx)	UOx will be quantified in 24-h samples	Day 2-3
Urinary Oxalate Levels (UOx)	UOx will be quantified in 24-h samples	Day 23-24

Secondary Outcome Measures

Outcome Measure	Time Frame
Total Fecal Oxalate Levels	Day 2-3
Total Fecal Oxalate Levels	Day 14
Total Fecal Oxalate Levels	Day 23-24
Urinary Calcium Levels	Day 2-3
Urinary Calcium Levels	Day 23-24
Sucralose Levels	Day 2-3
Sucralose Levels	Day 23-24
Calcium Oxalate (CaOx) Supersaturation Levels	Day 2-3
Calcium Oxalate (CaOx) Supersaturation Levels	Day 23-24
Plasma Oxalate Levels	Day 2-3
Plasma Oxalate Levels	Day 23-24

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Study Chair: Lama Nazzal, MD, NYU Langone Health; Principal Investigator: David Goldfarb, MD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2022
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: November 3, 2021
• First Submitted That Met QC Criteria: November 15, 2021
• First Posted (Actual): November 18, 2021

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 21-01274; R01DK128842 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Data collected for this study will be analyzed and stored at the Nazzal-hyperoxaluria data repository. After the study is completed, the de-identified, archived data will and stored at the Nazzal- hyperoxaluria data repository, under the supervision of Dr. Lama Nazzal, for use by other researchers including those outside of the study. Permission to transmit data to the Nazzal-hyperoxaluria data repository will be included in the informed consent.

Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) upon reasonable request.

• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• IPD Sharing Access Criteria: The investigator who proposed to use the data will have access to the data upon reasonable request. Requests should be directed to lama.nazzal@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No