A Pilot Study of Oxalate Absorption in Secondary Hyperoxaluria

Identify individuals with greater absorption of oxalate based on increase in urinary oxalate excretion in response to a controlled oxalate-rich test meal.

Study Overview

• Status: Completed
• Conditions: Nephrolithiasis; Kidney Stones; Hyperoxaluria; Secondary Hyperoxaluria
• Intervention / Treatment: Other: Test Meal

Detailed Description

This was a prospective 4-day study of oxalate absorption in subjects with secondary hyperoxaluria. Subjects visited the research center three times for outpatient visits (Screening, Test Day 3, Day 4).

Subjects were instructed to follow a low-oxalate diet, consuming only study-specified food choices that had low or no oxalate and controlled calcium content Days 1 through 4 (Baseline Period through the Day 4 clinic visit) and, on Test Day 3, consumed an oxalate-rich test meal.

Subjects performed three 24-hour urine collections during Screening, Baseline Day 2, and Test Day 3. Test Day 3 included the oxalate-rich test meal and the subject collected a 24-hour urine separated into 4 urine collection intervals. (Pre-test meal, post-test meal to 4 hours, 4-6 hours post test meal and remaining time to complete 24 hours).

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85741
      • Urological Associates of Southern Arizona, PC
  • Arkansas
    • Little Rock, Arkansas, United States, 72212
      • Applied Research Center of Arkansas, Inc.
  • Louisiana
    • Shreveport, Louisiana, United States, 71106
      • Regional Urology, LLC
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Omega Medical Research
  • Virginia
    • Virginia Beach, Virginia, United States, 23462
      • Urology of Virginia

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Males or non-pregnant and non-lactating females
• History of hyperoxaluria secondary to a known underlying enteric disease (e.g., Crohn's disease, bariatric surgery, and others) or without a known underlying cause (idiopathic), and kidney stones.
• Urinary oxalate ≥ 40 mg of oxalate/24 hr at screening.
• If taking drugs for the prevention of stone disease, including pyridoxine, thiazides (chlorthalidone, hydrochlorothiazide, and indapamide), citrate supplements, and allopurinol, there must have been no changes in these medications for at least one month prior to screening and no changes are anticipated for the duration of the study.
• Able to understand and provide written informed consent.

Exclusion Criteria:

• Under or over-collection on screening 24-hour urine collection (mg creatinine/kg body weight outside of gender-specific range).
• Estimated glomerular filtration rate (eGFR) <40 mL/minute/1.73 m^2 or acute renal failure.
• Primary hyperoxaluria.
• Allergy, intolerance, or any other factors limiting ability to consume the study foods or adhere to the study meal schedule.
• Positive pregnancy test during Screening.
• Clinically significant findings (including acute renal colic), an ongoing clinically significant illness requiring changes in management, or any planned medical/surgical procedure during the study.
• Malignancy undergoing active therapy; patients in remission on chronic suppressive or maintenance therapies are not excluded.
• Investigational compound within 30 days prior to screening.
• Investigator determined that the subject would not be able to adhere or to complete the study procedures , or could not discontinue Vitamin C supplements, calcium supplements, or other medications that could interfere with oxalate absorption and/or excretion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Test Meal; controlled oxalate-rich test meal	Other: Test Meal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Oxalate Absorption Normalized by Baseline Urinary Oxalate Excretion Over a 24 Hour Test Period	Percent of oxalate absorption normalized by baseline was calculated by 100*[UOx/test - UOx/baseline]/Ox intake from the test meal.	24 hours during baseline and test day following oxalate-rich meal

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Oxalate Absorption By Test Interval	Percent of Oxalate absorption by test interval was calculated as the urinary oxalate excretions (mg) during the test interval divided by the amount of oxalate in the test meal.	0-4 hours post test meal, 0-6 hours post test meal, 0-24 hours post test meal
Percent Change From Baseline for Urinary Oxalate to Creatinine Ratio by Test Interval	Urinary oxalate (UOx) excretion was normalized to units of mg/g creatinine by dividing the UOx in mg by the creatinine value in g from the same collection. Percent change from baseline for UOx/Cr from Baseline was calculated by 100 * [UOx/Cr for the test interval - UOx/Cr at Baseline] / UOx/Cr at Baseline.	24 hours during baseline, 0 to 4 hours post test meal, 0-6 hours post test meal, 6-24 hours post test meal, 0-24 hours post test meal

Collaborators and Investigators

• Sponsor: Allena Pharmaceuticals
• Investigators: Study Director: Annamaria Kausz, MD, MS, Allena Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: March 20, 2017
• First Submitted That Met QC Criteria: March 24, 2017
• First Posted (Actual): March 30, 2017

Study Record Updates

• Last Update Posted (Actual): October 28, 2021
• Last Update Submitted That Met QC Criteria: October 5, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Kidney Diseases; Nephrolithiasis; Kidney Stones; Urine Oxalate; Hyperoxaluria; Enteric Hyperoxaluria; Idiopathic Hyperoxaluria; Dietary Oxalate; urological Diseases; Oxalate Absorption
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Kidney Diseases; Urologic Diseases; Pathological Conditions, Anatomical; Neoplastic Processes; Urolithiasis; Urinary Calculi; Calculi; Neoplasm Metastasis; Kidney Calculi; Nephrolithiasis; Hyperoxaluria
• Other Study ID Numbers: ALLN-177-204

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No