Hyperoxaluria, Kidney Stones, Nephrolithiasis, Secondary Hyperoxaluria
Conditions
Keywords
Urine Oxalate, Nephrolithiasis, Kidney Stones, Hyperoxaluria, Enteric Hyperoxaluria, urological Diseases, Kidney Diseases, Dietary Oxalate, Idiopathic Hyperoxaluria, Oxalate Absorption
Brief summary
Identify individuals with greater absorption of oxalate based on increase in urinary oxalate excretion in response to a controlled oxalate-rich 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).
Interventions
OTHERTest Meal
Sponsors
Allena Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Oxalate Absorption Normalized by Baseline Urinary Oxalate Excretion Over a 24 Hour Test Period | 24 hours during baseline and test day following oxalate-rich meal | Percent of oxalate absorption normalized by baseline was calculated by 100\*\[UOx/test - UOx/baseline\]/Ox intake from the test meal. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Oxalate Absorption By Test Interval | 0-4 hours post test meal, 0-6 hours post test meal, 0-24 hours post test meal | 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. |
| Percent Change From Baseline for Urinary Oxalate to Creatinine Ratio by Test Interval | 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 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Enrolled Set The Enrolled Set included all subjects who were determined to be eligible for the study after screening assessments and were enrolled in the study. | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | Enrolled Set |
|---|---|
| Age, Continuous | 57.3 years STANDARD_DEVIATION 11.6 |
| BMI (kg/m^2) | 33.45 kg/m^2 STANDARD_DEVIATION 8.04 |
| Estimated glomerular filtration rate | 80.7 mL/minute/1.73 /m^2 STANDARD_DEVIATION 17.4 |
| Hyperoxaluria Classification Enteric Hyperoxaluria | 5 Participants |
| Hyperoxaluria Classification Idiopathic Hyperoxaluria | 17 Participants |
| Number of Kidney Stone Episodes at Study Entry | 5 Episodes STANDARD_DEVIATION 5.37 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 22 |
| other Total, other adverse events | 3 / 22 |
| serious Total, serious adverse events | 0 / 22 |
Outcome results
Primary
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.
Time frame: 24 hours during baseline and test day following oxalate-rich meal
Population: Enrolled set which included all enrolled subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Meal | Percent of Oxalate Absorption Normalized by Baseline Urinary Oxalate Excretion Over a 24 Hour Test Period | 2.84 percentage of oxalate absorption | Standard Deviation 2.36 |
Secondary
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.
Time frame: 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
Population: Enrolled set which included all enrolled subjects
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Test Meal | Percent Change From Baseline for Urinary Oxalate to Creatinine Ratio by Test Interval | 0-4 hours post test meal | 68.17 Percentage of change of UOx/Cr | Standard Deviation 93.05 |
| Test Meal | Percent Change From Baseline for Urinary Oxalate to Creatinine Ratio by Test Interval | 0-6 hours post test meal | 84.73 Percentage of change of UOx/Cr | Standard Deviation 100.05 |
| Test Meal | Percent Change From Baseline for Urinary Oxalate to Creatinine Ratio by Test Interval | 6-24 hours post test meal | 45.39 Percentage of change of UOx/Cr | Standard Deviation 62 |
| Test Meal | Percent Change From Baseline for Urinary Oxalate to Creatinine Ratio by Test Interval | 0-24 hours post test meal | 47.14 Percentage of change of UOx/Cr | Standard Deviation 64.82 |
Secondary
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.
Time frame: 0-4 hours post test meal, 0-6 hours post test meal, 0-24 hours post test meal
Population: Enrolled set which included all enrolled subjects
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Test Meal | Percent of Oxalate Absorption By Test Interval | 0-4 Hours post test meal | 2.11 percentage of oxalate absorption | Standard Deviation 0.52 |
| Test Meal | Percent of Oxalate Absorption By Test Interval | 0-6 hours post test meal | 3.55 percentage of oxalate absorption | Standard Deviation 0.88 |
| Test Meal | Percent of Oxalate Absorption By Test Interval | 0-24 hours post test meal | 10.83 percentage of oxalate absorption | Standard Deviation 3.04 |