A Pilot Study of Oxalate Absorption in Secondary Hyperoxaluria
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Test Meal controlled oxalate-rich test meal |
Other: Test Meal
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Urological Associates of Southern Arizona, PC | Tucson | Arizona | United States | 85741 |
| 2 | Applied Research Center of Arkansas, Inc. | Little Rock | Arkansas | United States | 72212 |
| 3 | Regional Urology, LLC | Shreveport | Louisiana | United States | 71106 |
| 4 | Omega Medical Research | Warwick | Rhode Island | United States | 02886 |
| 5 | Urology of Virginia | Virginia Beach | Virginia | United States | 23462 |
Sponsors and Collaborators
- Allena Pharmaceuticals
Investigators
- Study Director: Annamaria Kausz, MD, MS, Allena Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ALLN-177-204
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Test Meal |
|---|---|
| Arm/Group Description | controlled oxalate-rich test meal |
| Period Title: Overall Study | |
| STARTED | 22 |
| COMPLETED | 22 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Enrolled Set |
|---|---|
| Arm/Group Description | The Enrolled Set included all subjects who were determined to be eligible for the study after screening assessments and were enrolled in the study. |
| Overall Participants | 22 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
57.3
(11.6)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
12
54.5%
|
| Male |
10
45.5%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
2
9.1%
|
| White |
20
90.9%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| BMI (kg/m^2) (kg/m^2) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [kg/m^2] |
33.45
(8.04)
|
| Estimated glomerular filtration rate (mL/minute/1.73 /m^2) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [mL/minute/1.73 /m^2] |
80.7
(17.4)
|
| Hyperoxaluria Classification (Count of Participants) | |
| Idiopathic Hyperoxaluria |
17
77.3%
|
| Enteric Hyperoxaluria |
5
22.7%
|
| Number of Kidney Stone Episodes at Study Entry (Episodes) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [Episodes] |
5
(5.37)
|
Outcome Measures
| Title | Percent of Oxalate Absorption Normalized by Baseline Urinary Oxalate Excretion Over a 24 Hour Test Period |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Enrolled set which included all enrolled subjects |
| Arm/Group Title | Test Meal |
|---|---|
| Arm/Group Description | controlled oxalate-rich test meal |
| Measure Participants | 22 |
| Mean (Standard Deviation) [percentage of oxalate absorption] |
2.84
(2.36)
|
| Title | Percent of Oxalate Absorption By Test Interval |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Enrolled set which included all enrolled subjects |
| Arm/Group Title | Test Meal |
|---|---|
| Arm/Group Description | controlled oxalate-rich test meal |
| Measure Participants | 22 |
| 0-4 Hours post test meal |
2.11
(0.52)
|
| 0-6 hours post test meal |
3.55
(0.88)
|
| 0-24 hours post test meal |
10.83
(3.04)
|
| Title | Percent Change From Baseline for Urinary Oxalate to Creatinine Ratio by Test Interval |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Enrolled set which included all enrolled subjects |
| Arm/Group Title | Test Meal |
|---|---|
| Arm/Group Description | controlled oxalate-rich test meal |
| Measure Participants | 22 |
| 0-4 hours post test meal |
68.17
(93.05)
|
| 0-6 hours post test meal |
84.73
(100.05)
|
| 6-24 hours post test meal |
45.39
(62)
|
| 0-24 hours post test meal |
47.14
(64.82)
|
Adverse Events
| Time Frame | 34 days (adverse events were recorded from the time of informed consent until the last study visit, and the screening period was approximately 30 days) | |
|---|---|---|
| Adverse Event Reporting Description | Since no investigational product was administered; no drug-related adverse events (AEs) occurred. The investigator assessed AEs by intensity (severity) and causality in relation to the study intervention, which was the study diet. Any untoward symptoms or worsening of medical conditions reported during the study were recorded as AEs. | |
| Arm/Group Title | Test Meal | |
| Arm/Group Description | controlled oxalate-rich test meal | |
All Cause Mortality |
||
| Test Meal | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/22 (0%) | |
Serious Adverse Events |
||
| Test Meal | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/22 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Test Meal | ||
| Affected / at Risk (%) | # Events | |
| Total | 3/22 (13.6%) | |
| Musculoskeletal and connective tissue disorders | ||
| Arthritis | 1/22 (4.5%) | 1 |
| Trigger finger | 1/22 (4.5%) | 1 |
| Nervous system disorders | ||
| Headache | 1/22 (4.5%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Allena Medical Affairs |
|---|---|
| Organization | Allena Pharmaceuticals, Inc |
| Phone | 6174674577 |
| AllenaMedInfo@allenapharma.com |
- ALLN-177-204