MOx Diet for Enteric Hyperoxaluria

Overseen By David Goldfarb, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: NYU Langone Health

Must not be taking: Antibiotics

Disqualifiers: Pregnancy, Colectomy, IBD flare, others

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

Compensation: Varies

Number of Visits: Unknown

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how a moderately high oxalate diet (MOx Diet, found in foods like spinach) affects individuals with enteric hyperoxaluria, a condition linked to kidney stones, compared to healthy individuals. Researchers aim to understand the diet's impact on the digestive system and kidney stone formation. Participants will undergo a series of diet changes and provide samples such as stool, urine, and blood. Suitable candidates include those with inflammatory bowel disease (IBD) or those more than six months post-gastric bypass surgery who have experienced kidney stones in the last three years. Healthy individuals without chronic illnesses or a history of kidney stones are also needed for comparison. As an unphased trial, this study allows participants to contribute to foundational research that could lead to improved dietary recommendations for preventing kidney stones.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, healthy controls must not be on any chronic medications to participate.

What prior data suggests that the MOx Diet is safe for participants?

Research has shown that individuals with enteric hyperoxaluria, a condition characterized by excessive oxalate in the urine, may absorb more than 30% of dietary oxalate. In contrast, healthy individuals absorb less than 10%. Although specific safety information about the moderately high oxalate (MOx) diet is limited, the effects of oxalate on the body are well-documented. Oxalate, a natural substance in many foods, can lead to kidney stones if consumed in excess.

The MOx diet involves consuming foods with higher oxalate levels, such as spinach, as part of the study's approach. This study is in a preliminary phase, focusing on understanding effects rather than confirming long-term safety. Participants may notice changes in urine oxalate levels, which the study will monitor. It is important for participants to follow the trial's guidelines carefully and report any concerns to the study team. ^{1 2 3 4 5}

Why are researchers excited about this trial?

The MOx Diet is unique because it offers a dietary approach to managing enteric hyperoxaluria, which is different from typical treatments like medications or supplements aimed at reducing oxalate absorption. Unlike standard of care options, which often involve medications such as calcium supplements or enzyme therapies, the MOx Diet focuses on modifying the intake of oxalate through a moderately high oxalate diet. Researchers are excited about this approach because it could provide a more natural and potentially sustainable way to manage the condition, reducing dependence on pharmaceutical interventions. Moreover, exploring dietary interventions might offer insights into how diet can be used to manage or even prevent symptoms, offering a new perspective for patient care.

What evidence suggests that the MOx Diet might be an effective treatment for enteric hyperoxaluria?

Research has shown that a diet low in oxalates can significantly reduce urinary oxalate levels, which are linked to kidney stones. For example, one study found a significant decrease in urinary oxalate when participants followed a low-oxalate diet. This suggests that controlling oxalate intake through diet might help manage conditions like enteric hyperoxaluria, characterized by excessive oxalate in the urine. The MOx Diet trial will compare a diet with moderately high oxalate levels in individuals with enteric hyperoxaluria to healthy controls. Understanding how the body processes oxalate could aid in preventing kidney stones in the future. ^{2 3 5 6 7}

Who Is on the Research Team?

Lama Nazzal, MD

Principal Investigator

NYU Langone Health

David Goldfarb, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

Adults aged 18-80 with IBD or post-RYGB surgery, who've had a kidney stone or related event in the last three years can join. It's open to all races and genders but not for pregnant/nursing women, those with recent antibiotics use, colectomy patients, active IBD flare-ups, or significantly impaired kidney function.

Inclusion Criteria

My gender or race does not exclude me from this trial.

I have IBD or had gastric bypass surgery over 6 months ago and experienced a kidney stone event or saw a stone on an image in the last 3 years.

Exclusion Criteria

I have had a flare-up of my inflammatory bowel disease in the last 3 months.

My kidney function, measured by eGFR, is below 60 ml/min/1.73 m2.

I have not been frequently taking antibiotics for perianal disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dietary Intervention

Participants are administered a high oxalate diet on Days 0-3 and Days 21-24, with a washout period on Days 4-7, and 250mg sodium oxalate on Days 8-20

24 days

Multiple visits for dietary administration and sample collection

Sample Collection

Participants partake in four stool collections, four 24-h urine collections, two blood collections, and four sets of colonic permeability testing

Throughout the intervention period

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Moderately High Oxalate (MOx) Diet

Trial Overview The trial tests how a high oxalate diet affects individuals with Enteric Hyperoxaluria compared to healthy controls. Participants will follow specific diets and undergo stool and urine collections, blood tests, and intestinal health assessments at Weil Cornell Medicine.

How Is the Trial Designed?

Group I: Enteric Hyperoxaluria Experimental Treatment 1 Intervention

Group II: Healthy Controls Active Control 1 Intervention

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

A low-oxalate diet significantly reduced urinary oxalate levels more effectively than supplementation with vitamin B6 and magnesium in patients with idiopathic hyperoxaluria, with a median reduction of 31.1% compared to 16.0% for supplementation alone.

Combination therapy of a low-oxalate diet and supplementation did not provide additional benefits over the diet alone, indicating that dietary modification is the preferred approach for managing urinary oxalate levels in stone formers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Randomized Evaluation of Idiopathic Hyperoxaluria Treatments. Gupta, M., Gallante, B., Bamberger, JN., et al.[2022]

Hyperoxaluria (HOx), which can lead to kidney stones and other complications, is often linked to low-calcium diets and can be classified into dietary, enteric, or primary types, with primary hyperoxaluria being the most severe and genetically inherited.

Advancements in early biochemical and genetic diagnosis for primary hyperoxaluria have significantly improved patient outcomes, allowing for better management and treatment strategies to prevent progression to end-stage renal failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The Hyperoxalurias]. Marangella, M., Petrarulo, M., Bermond, F., et al.[2017]

A study of 26 commercial enteral nutrition formulas found that oxalate concentrations varied widely, from 4 to 140 mg oxalate per liter, which can lead to significant daily oxalate intake for patients requiring nutrition support.

Patients using these formulas could consume between 12 to 150 mg of oxalate per day, increasing their risk for hyperoxaluria and calcium oxalate kidney stones, especially if calcium intake is low or gastrointestinal absorption is impaired.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxalate Content of Enteral Nutrition Formulas. Penniston, KL., Palmer, EA., Medenwald, RJ., et al.[2020]

Oral calcium supplementation effectively reduced urinary oxalate excretion to normal levels in patients with enteric hyperoxaluria, as observed in a study of three patients with a history of renal stones after ileal resection.

When two patients reduced their calcium intake on their own, they experienced a return of hyperoxaluria and developed renal stones again, suggesting that maintaining an adequate dose of calcium is crucial for preventing stone formation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral calcium supplement decreases urinary oxalate excretion in patients with enteric hyperoxaluria. Takei, K., Ito, H., Masai, M., et al.[2017]

A low-oxalate, low-fat diet significantly reduced urinary oxalate excretion in 10 patients with hyperoxaluria, from an average of 1.1 to 0.7 mmol/24 h, indicating its efficacy in managing this condition.

The study suggests that while the diet is challenging, it is manageable for patients, and emphasizes the importance of regular dietary guidance from a dietitian for successful implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-oxalate, low-fat dietary regimen in hyperoxaluria following jejunoileal bypass. Nordenvall, B., Backman, L., Burman, P., et al.[2013]

A 59-year-old female patient with chronic kidney disease (CKD) due to enteric hyperoxaluria (EH) underwent combined intestine-kidney transplantation (CIKTx) after two failed kidney transplants, but experienced recurrence of EH and kidney dysfunction post-surgery.

The study suggests that kidney transplantation alone is not advisable for patients with CKD from EH due to a high risk of recurrence, highlighting the need for careful consideration of oxalate transport mechanisms in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrence of Hyperoxaluria and Kidney Disease after Combined Intestine-Kidney Transplantation for Enteric Hyperoxaluria. Ekser, B., Mangus, RS., Kubal, CA., et al.[2018]

In a study of 59 children with calcium urolithiasis, plasma oxalate (POx) levels were significantly higher in those with secondary hyperoxaluria compared to healthy controls, indicating a potential link between elevated POx and kidney stone disease.

Children with calcium urolithiasis but normal urinary oxalate excretion did not show increased POx levels, suggesting that elevated POx may be associated with intestinal oxalate hyperabsorption in those with secondary hyperoxaluria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma oxalate level in pediatric calcium stone formers with or without secondary hyperoxaluria. Sikora, P., Beck, B., Zajaczkowska, M., et al.[2021]

Increasing fluid intake in patients with bowel disease significantly improved urine volume and reduced calcium oxalate supersaturation, which is important for preventing kidney stones.

Alkali supplementation and advice to reduce oxalate absorption did not show effectiveness in lowering calcium oxalate supersaturation, indicating that these interventions may not be beneficial for stone prevention in this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What treatments reduce kidney stone risk in patients with bowel disease? Bianco, J., Chu, F., Bergsland, K., et al.[2023]

Citations

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

Impact of low‐oxalate diet on hyperoxaluria among ... The result of this study showed a significant (p = .000) decrease in urinary oxalate with the help of a low‐oxalate diet as shown in Table 3.

2. evidence.nejm.org evidence.nejm.org/doi/full/10.1056/EVIDoa2100053

Randomized Placebo-Controlled Trial of Reloxaliase in ... Reloxaliase treatment for 4 weeks reduced UOx excretion in patients with enteric hyperoxaluria; adverse events were relatively common, but not dose-limiting.

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

Dietary oxalate and kidney stone formation - PMC We have shown that reducing dietary calcium from 1,000 to 400 mg/day on a 250 mg/day oxalate diet increases mean oxalate excretion by 20.3% in colonized ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06331546?cond=Oxalates&viewType=Table&rank=4

Gut Oxalate Absorption in Calcium Oxalate Stone Disease 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, ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/fsn3.4088

Impact of low‐oxalate diet on hyperoxaluria among ... The result of this study showed a significant (p = .000) decrease in urinary oxalate with the help of a low-oxalate diet as shown in Table 3.

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK558987/

Hyperoxaluria - StatPearls - NCBI Bookshelf Enteric hyperoxaluria patients are also advised to consume a low-fat diet, calcium and citrate supplements, and a restriction of oxalate-rich foods.[13] Calcium ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2210740124000433

Pathophysiology and management of enteric hyperoxaluria Enteric hyperoxaluria (EH) is a metabolic disorder characterized by an increased output of oxalate in urine, primarily due to an increased absorption of ...