Efficacy of a Gluten-free Diet in Difficult to Manage Nephrotic Syndrome: Utility of Plasma Zonulin Levels as a Predictive Biomarker

Study Overview
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Brief Summary
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Elevated plasma zonulin levels, which are supportive of a diagnosis of CD (celiac disease) in children with gastrointestinal symptoms, may indicate patients with difficult-to-manage NS who will benefit from initiation of a GFD (gluten free diet). This pilot study will determine whether high plasma zonulin levels can be used as a screening tool to identify patients with NS (nephrotic syndrome) who are likely to demonstrate a beneficial response to a GFD. It will provide important information about the feasibility of testing the efficacy of a GFD for this condition and assist in the design and sample size calculation for a definitive trial to test the beneficial effect of this dietary intervention. Although NS is a rare condition in childhood, it is a chronic disease that can lead to short- and long-term disability especially in those with difficult-to-manage disease. There is an urgent need to develop safe and effective new therapies in this subgroup. This project may indicate the utility of a common dietary modification, a GFD, to treat these patients. The growing medical use of and greater access to gluten-free food items underscore the feasibility and timeliness of this approach.

Official Title
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Efficacy of a Gluten-free Diet in Difficult to Manage Nephrotic Syndrome: Utility of Plasma Zonulin Levels as a Predictive Biomarker

Conditions
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Nephrotic Syndrome

Intervention / Treatment
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* Other: Implementation of a gluten-free diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Steroid sensitive NS: complete remission of proteinuria in response to administration of a standard course of corticosteroids Difficult-to-manage NS: disease that cannot be controlled without incurring intolerable side effects from currently available immunosuppressive agents, namely corticosteroids, calcineurin inhibitors, mycophenolate mofetil, or rituximab. Patients with biopsy-proven MCD or FSGS will be eligible as long as they have steroid sensitive disease. However, a renal biopsy will not be required for enrollment into the trial. Exclusion Criteria: Any patient diagnosed with nephrotic syndrome that is not considered steroid sensitive or frequently relapsing Pre-existing celiac disease or gastro-intestinal disorder that precludes use of a GFD

Ages Eligible for Study
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Minimum Age: 9 Months
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| zonulin ≤17.5 ng/ml<br>Pediatric patients with difficult-to-manage nephrotic syndrome will be stratified based on the plasma zonulin concentration into two groups | Other: Implementation of a gluten-free diet<br>* Patients will be placed on gluten free diet for 9-12 months.<br>|
| zonulin >17.5 ng/ml<br>Pediatric patients with difficult-to-manage nephrotic syndrome will be stratified based on the plasma zonulin concentration into two groups | Other: Implementation of a gluten-free diet<br>* Patients will be placed on gluten free diet for 9-12 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in disease activity measured by relapse rate | Response is defined as a ≥50%decrease in relapse rate | 12 Months | 
| Change in disease activity measured by change in dosage of corticosteroids and immunosuppressive medications | reduction by ≥1 drug in exposure to immunosuppressive medications in response to the GFD | 12 Months |