Endogenous Oxalate Synthesis in Idiopathic Calcium Oxalate Kidney Stone Disease

NCT ID: NCT06989320

Last Updated: 2025-05-31

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-27
• Study Completion Date: 2031-12-31

Brief Summary

The goal of this clinical trial study is to test if patients with idiopathic calcium oxalate kidney stones have an increased production of oxalate by the body, 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 amounts of oxalate for 5 days ingest a soluble form of glycolate and vitamin C collect urine, blood, stool during the dietary and oral dosing portions of the study and also collect breath sample during the oral glycolate test

Detailed Description

In this study the investigators propose to measure the production of oxalate by the body (endogenous oxalate synthesis), after equilibration on a low oxalate diet (<60 mg oxalate/day, 600-800 mg calcium/day) and estimate the importance of vitamin C and glycolate metabolism to oxalate production in both Calcium Oxalate Kidney Stone patients and matched controls by oral dosings of those two substances.

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-hour urine specimens collected at home on self-choice diets and anthropometric measurements.

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

Phase 2. Oxalate production and 13C-glycolate dosing tests. On Day 5, participants will arrive after an overnight fast in the research unit to undergo the oral 13C-glycolate dosing test. After a 1-hour baseline urine collection, they will ingest an oral load containing 0.5 mg/kg body weight of 13C-glycolate, dissolved in bottled water. For the next 7 hours, blood and urine will be collected hourly, and breath as more time points. They will remain on the fixed diet for 24 hours with a meal 7 hours post-load, and dinner at home 12 hours post-load. They will collect the remainder of their 24-hour urine at home.

Phase 3. Oxalate production and 13C-ascorbic acid dosing tests. After 1 day of equilibration on the same low-oxalate diet, participants will arrive after an overnight fast in the research unit to provid eone blood and one urine sample and then ingest an oral dose of 13C-ascorbic acid (0.75 mg/kg), return home and continue to ingest the low-oxalate diet. The next morning, participants will arrive after an overnight fast in the research unit. For the next 7 hours, blood and urine will be collected hourly. They will remain on the fixed diet for 24 hours with a meal at the end of the visit.

Conditions

Kidney Stones; Kidney Calculi; Urolithiasis; Urolithiasis, Calcium Oxalate; Nephrolithiasis; Nephrolithiasis, Calcium Oxalate; Oxalate Urolithiasis; Healthy; Healthy Volunteer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Idiopathic Calcium Oxalate Kidney Stone Patients

Low oxalate fixed diets. oral glycolate and ascorbic acid administration

Group Type: EXPERIMENTAL

Low-oxalate diet and glycolate dosing

Intervention Type: DIETARY_SUPPLEMENT

Low-oxalate diet 4 days of fixed eucaloric diet with low oxalate (\<60 mg/day), normal calcium content (600-1000 mg/day)

Oral glycolate dosing

Intervention Type: DIETARY_SUPPLEMENT

Oral 13C-glycolate dosing (0.5 mg/kg)

Oral 13C- ascorbic acid dosing

Intervention Type: DIETARY_SUPPLEMENT

Oral 13C- ascorbic acid dosing (0.75 mg/kg)

Healthy non-kidney stone forming individuals

Low oxalate fixed diets. oral glycolate and ascorbic acid administration

Group Type: ACTIVE_COMPARATOR

Low-oxalate diet and glycolate dosing

Intervention Type: DIETARY_SUPPLEMENT

Low-oxalate diet 4 days of fixed eucaloric diet with low oxalate (\<60 mg/day), normal calcium content (600-1000 mg/day)

Oral glycolate dosing

Intervention Type: DIETARY_SUPPLEMENT

Oral 13C-glycolate dosing (0.5 mg/kg)

Oral 13C- ascorbic acid dosing

Intervention Type: DIETARY_SUPPLEMENT

Oral 13C- ascorbic acid dosing (0.75 mg/kg)

Interventions

Low-oxalate diet and glycolate dosing

Low-oxalate diet 4 days of fixed eucaloric diet with low oxalate (\<60 mg/day), normal calcium content (600-1000 mg/day)

Intervention Type: DIETARY_SUPPLEMENT

Oral glycolate dosing

Oral 13C-glycolate dosing (0.5 mg/kg)

Intervention Type: DIETARY_SUPPLEMENT

Oral 13C- ascorbic acid dosing

Oral 13C- ascorbic acid dosing (0.75 mg/kg)

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• age 18-80 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Texas, Southwestern Medical Center at Dallas

OTHER

Sponsor Role: collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Sonia Fargue

Associate professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sonia Fargue, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

United States, Alabama University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status: RECRUITING

University of Texas South Western Medical Center

Dallas, Texas, United States

Site Status: NOT_YET_RECRUITING

Countries

United States

Central Contacts

Sonia Fargue, PhD

Role: CONTACT

sfargue@uabmc.edu

205-975-6932

Facility Contacts

Sonia Fargue, PhD

Role: primary

sfargue@uabmc.edu

205-975-6932

Research Coordinator

Role: backup

kidneystone@uabmc.edu

205-934-5712

Naim Maalouf, MD

Role: primary

Naim.Maalouf@UTSouthwestern.edu

Research Coordinator

Role: backup

Esperanza.Jackson@UTSouthwestern.edu

Other Identifiers

R01DK137784

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB300014279-OSS

Identifier Type: -

Identifier Source: org_study_id