Gut Oxalate Absorption in Calcium Oxalate Stone Disease

Healthy Clinical Trial

Official title:

Gastrointestinal Oxalate Absorption in Calcium Oxalate Stone Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06331546
• Other study ID #: IRB300004693
• Secondary ID: R01DK137784
• Status: Recruiting
• Phase: N/A
• Start date: April 17, 2024
• Est. completion date: December 31, 2031

Study information

• Verified date: May 2024
• Source: University of Alabama at Birmingham
• Contact: Sonia Fargue, PhD
• Phone: 2059756932
• Email: sfargue[@]uabmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial study is to test if patients with idiopathic calcium oxalate kidney stones have an increased absorption of dietary oxalate, which would lead to increased urinary excretion of oxalate.

The study will recruit adult patients with a history of calcium oxalate kidney stones and healthy volunteers without kidney stones.

Participants will

• ingest fixed diets containing low and moderately high amounts of oxalate for 5 days at a time

• ingest a soluble form of oxalate and sugar preparations to test gut permeability

• collect urine, blood, stool and breath sample during the fixed diets and the soluble oxalate test

Description:

In this study the investigators propose to measure the net gastrointestinal absorption of oxalate both by food-bound oxalate, using low- (<60 mg/day) and high- (250-300 mg/day) oxalate diets (600-800 mg daily calcium in both), and by the soluble 13C2-oxalate oral test in both Calcium Oxalate Kidney Stone patients and matched controls.

Phase 1. Screening and low-oxalate diet 24-hr urinary excretions. Between the University of Alabama at Birmingham (UAB) and the University of Texas Southwestern Medical Center (UTSW), the study will enroll 40 subjects with idiopathic Calcium Oxalate Kidney Stone (20 Males/20 Females) and 40 non-kidney stone forming controls (20 Males/20 Females). Participants in the two groups will be matched for age (within 10 yrs) and gender. Screening will include blood complete metabolic profile and two 24-hr urine specimens collected at home on self-choice diets and anthropometric measurements.

Participants will then ingest the controlled low-oxalate (<60 mg/d) diet for 5 consecutive days and collect two 24-hr urines after 2 days of dietary equilibration.

Phase 2. 13C2-Oxalate gut absorption tests. On Day 5, participants will arrive after an overnight fast in the research unit to undergo the 13C2-oxalate absorption test. After a 1-hour baseline urine collection, they will ingest an oral load containing 100 mg 13C2-oxalate and 1 g sucralose, dissolved in bottled water. For the next 9 hrs, blood and urine will be collected hourly, and breath as more time points. They will remain on the fixed diet for 24 hrs with a breakfast 2 hours after the load, lunch 6 hrs post-load, and dinner at home 12 hrs post-load. They will collect the remainder of their 24-hr urine at home and the totality of the stool eliminated during the first 24 hrs after the load using kits provided.

Phase 3. High-oxalate diet 24-hr urinary excretions. After a minimum of 1 week wash-out period, during which participants will eat freely, participants will consume the high oxalate (250-300 mg/day) diet for the next 4 days. Two 24-hr urine specimens will be collected after 2 days of equilibration and a fasting blood draw on the morning of Day 5.

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Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 31, 2031
• Est. primary completion date: December 31, 2030
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• age 18-70 yrs

• Body Mass Index > 18.5 kg/m2

• Normal fasting serum electrolytes on comprehensive metabolic profile

• Willing to ingest fixed diets

• Willing to stop supplements (vitamins including vitamin C, calcium (citrate or carbonate) and other minerals, herbal supplements, nutritional aids, probiotics) for 2 weeks before start and during study.

• For stone formers: first time or recurrent Calcium Oxalate stone former. Composition of most recent stone = 50% calcium oxalate if available, uric acid component <20%

Exclusion Criteria:

• Chronic Kidney Disease stage 4-5

• Primary hyperoxaluria, Enteric (secondary) hyperoxaluria

• Liver, bowel, endocrine or renal diseases (other than idiopathic Calcium Oxalate kidney stones) or any other condition that may influence the absorption, transport or urinary excretion of ions, which will compromise the interpretation of results, including: Cystic fibrosis, Celiac disease, Cystinuria, Uric acid stone former, Nephrotic syndrome, Sarcoidosis, Renal tubular acidosis, Primary hyperparathyroidism, Neurogenic bladder, Urinary diversion, Chronic diarrhea, Bariatric surgery, Inflammatory bowel disease

• Pregnancy or breast-feeding

• Incompatible dietary requirements with the study, food allergies or intolerance to any of the foods in study menus

• Active malignancy or treatment for malignancy within 12 months prior to screening

• Utilization of immunosuppressive medication

• Uncontrolled hypertension or diabetes

• Diabetes type 1

• Chronic NSAID use

Related Conditions & MeSH terms

• Calculi
• Healthy
• Kidney Calculi
• Kidney Stone
• Nephrolithiasis
• Nephrolithiasis, Calcium Oxalate
• Oxaluria
• Urinary Calculi
• Urolithiasis
• Urolithiasis, Calcium Oxalate

Intervention

Dietary Supplement:
• Low-oxalate diet
4 days of fixed eucaloric diet with low oxalate (<60 mg/day), normal calcium content (600-1000 mg/day)
• High-oxalate diet
4 days of fixed eucaloric diet with moderately high oxalate (250-300 mg/day), normal calcium content (600-1000 mg/day)

Other:
• soluble oxalate gut absorption test
Oral ingestion of 13C2-oxalate and sucralose.

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	UTSW	Dallas	Texas

Sponsors (3)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of Texas Southwestern Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Net Gastrointestinal absorption of food-bound oxalate	difference between 24-hour urinary oxalate excretion on the high oxalate diet and the low oxalate diet, normalized to the difference in dietary oxalate composition of the two diets (%)	4 day
Secondary	Absorption of soluble 13C2-oxalate	Proportion of 13C2-oxalate recovered in urine to the amount orally ingested (%)	1 day
Secondary	Estimated endogenous oxalate synthesis (oxalate mg/day)	24-hour urinary oxalate excretion on the low oxalate diet (mg/day)	2 days