Oxalate Synthesis for Kidney Stones

Recruiting at 1 trial location

Overseen By Sonia Fargue, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Must not be taking: Immunosuppressants

Disqualifiers: Chronic kidney disease, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether individuals with idiopathic calcium oxalate kidney stones produce more oxalate, resulting in higher urinary levels. Participants will adhere to a low-oxalate diet and take glycolate (an oral supplement) and vitamin C to observe oxalate processing in their bodies. The study includes both kidney stone patients and healthy volunteers. It suits those who have experienced calcium oxalate kidney stones or are healthy without stones and are willing to follow a prescribed diet and pause their supplements. As an unphased trial, this study allows participants to contribute to the scientific understanding of kidney stone formation and management.

Do I have to stop taking my current medications for the trial?

The trial requires you to stop taking supplements like vitamins, calcium, and herbal products for 2 weeks before and during the study. It doesn't specify if you need to stop other medications, so it's best to ask the trial team for more details.

What prior data suggests that this protocol is safe for participants?

Research has shown that the treatments in this trial are generally safe for people.

For the low-oxalate diet and glycolate dosing, evidence suggests that a low-oxalate diet can lower the risk of kidney stones. However, some groups have not shown a strong connection between dietary oxalate and kidney stones. This indicates that while the diet is safe, its effectiveness may vary among individuals.

Studies on taking vitamin C (oral 13C-ascorbic acid) suggest that high doses can increase oxalate in urine, particularly in men. However, moderate amounts of vitamin C are usually safe for most people.

Early studies on oral glycolate dosing, using a similar compound called LLX-424, found it to be safe and effective in blocking an enzyme linked to kidney stone formation.

Overall, previous studies have shown these treatments to be safe, but individual responses can vary. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for kidney stones, which often include pain relievers, increased hydration, and in some cases, surgery or shock wave therapy, this new approach focuses on dietary and metabolic interventions. Researchers are excited about the potential of a low-oxalate diet combined with oral dosing of glycolate and 13C-ascorbic acid, as it targets the root cause by reducing oxalate levels in the body. This method is distinctive because it aims to prevent stone formation rather than just managing symptoms or removing existing stones. By addressing oxalate synthesis directly, this treatment could offer a non-invasive, sustainable solution for preventing kidney stones, which is a promising shift from current options.

What evidence suggests that this trial's treatments could be effective for kidney stones?

This trial will compare the effects of different interventions on oxalate synthesis in kidney stone patients and healthy individuals. Research has shown that a low-oxalate diet can reduce the risk of developing calcium oxalate kidney stones. Studies have found that reducing oxalate intake lowers urinary oxalate levels, which are linked to kidney stone formation. For instance, one study discovered that increased oxalate consumption raised urinary oxalate levels, suggesting that reducing intake could have the opposite effect.

Participants in this trial will receive oral glycolate dosing. Research indicates that the body can convert glycolate into oxalate, affecting oxalate levels. In conditions like primary hyperoxaluria, where the body produces excess oxalate, managing glycolate processing might help prevent stone formation.

Additionally, the trial will assess the impact of oral 13C-ascorbic acid dosing. While vitamin C (ascorbic acid) generally benefits health, it can also convert into oxalate in the body. Some studies have noted that high vitamin C intake might increase the risk of kidney stones in certain individuals. Therefore, monitoring vitamin C intake could be important for those at risk of stones. ^{2 4 6 7 8}

Who Is on the Research Team?

Sonia Fargue, PhD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for adults who've had calcium oxalate kidney stones and healthy volunteers without a history of these stones. Participants will follow a special low-oxalate diet, take glycolate and vitamin C, and provide urine, blood, stool, and breath samples.

Inclusion Criteria

Body Mass Index > 18.5 kg/m2

Normal fasting serum electrolytes on comprehensive metabolic profile

Willing to ingest fixed diets

Exclusion Criteria

My kidney function is severely reduced.

Pregnancy or breast-feeding

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Dietary Equilibration

Participants ingest a controlled low-oxalate diet for 5 consecutive days and collect two 24-hour urines after 2 days of dietary equilibration.

5 days

Daily monitoring (in-person and at home)

13C-glycolate Dosing Test

Participants undergo the oral 13C-glycolate dosing test with hourly blood and urine collections for 7 hours.

1 day

1 visit (in-person)

13C-ascorbic Acid Dosing Test

Participants ingest an oral dose of 13C-ascorbic acid and undergo hourly blood and urine collections for 7 hours the next day.

2 days

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Low-oxalate diet and glycolate dosing
• Oral 13C- ascorbic acid dosing
• Oral glycolate dosing

Trial Overview The study tests if people with idiopathic calcium oxalate kidney stones produce more body-made oxalate leading to higher levels in the urine. It involves controlled diets and dosing with oral glycolate and vitamin C to track changes.

How Is the Trial Designed?

Group I: Idiopathic Calcium Oxalate Kidney Stone Patients Experimental Treatment 3 Interventions

Low oxalate fixed diets. oral glycolate and ascorbic acid administration

Group II: Healthy non-kidney stone forming individuals Active Control 3 Interventions

Low oxalate fixed diets. oral glycolate and ascorbic acid administration

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

University of Texas, Southwestern Medical Center at Dallas

Collaborator

Trials

18

Recruited

21,200+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7551439/

Dietary Oxalate Intake and Kidney Outcomes - PMC The increased load of dietary oxalate presented to the kidneys has been linked to different kidney-related conditions and injuries.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04437225

NCT04437225 | Renal Metabolism of Glycolate to Oxalate This study will determine the contribution of glycolate metabolism to urinary oxalate excretion in healthy subjects, using carbon 13 isotope glycolate tracer ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0085253815474629

Contribution of dietary oxalate to urinary oxalate excretion Increasing dietary oxalate from 50 mg per day to 250 mg increased the mean oxalate excretion of the group by 34.9% (P = 0.001). The importance of the dietary ...

4. cariguidelines.org cariguidelines.org/nutrition-therapy-for-the-prevention-of-kidney-stones/

Nutrition therapy for the prevention of kidney stones There is limited evidence that a low oxalate diet reduces the risk of calcium oxalate stones. Alternatively, reducing bioavailability of dietary ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11167185/

Impact of low‐oxalate diet on hyperoxaluria among ... The results showed that a low‐oxalate diet had a positive effect on patients suffering from nephrolithiasis. Furthermore, after treatment, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6459305/

Dietary oxalate and kidney stone formation - PMC In this review we discuss dietary oxalate absorption, degradation, and excretion and its potential impact on kidney stone growth.

7. ajkd.org ajkd.org/article/S0272-6386(23)00670-4/fulltext

Kidney Stone Pathophysiology, Evaluation and Management Values >400mg/d may limit risk for calcareous stones, with even higher levels sometimes needed. pH. •. Values <6.0 may increase the risk of uric ...

8. mdpi.com mdpi.com/2072-6643/12/9/2673

Dietary Oxalate Intake and Kidney Outcomes Furthermore, no association was found between dietary oxalate intake and the risk for kidney stones in younger women. This may suggest that dietary oxalate ...