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Effect of Daily Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) on Proteinuria in Pediatric Patients With Idiopathic Nephrotic Syndrome

Not Applicable
Completed
Conditions
Frequently Relapsing Nephrotic Syndrome
Idiopathic Nephrotic Syndrome
Interventions
Device: Transcutaneous Auricular Vagus Nerve (taVNS) stimulation
Registration Number
NCT04169776
Lead Sponsor
Northwell Health
Brief Summary

This study evaluates the impact of transcutaneous auricular Vagus Nerve stimulation (taVNS) therapy on the incidence of nephrotic syndrome relapses in children with idiopathic nephrotic syndrome. Participants will perform taVNS 5 minutes a day for 6 months total, monitoring for signs of nephrotic syndrome relapse with both labwork and clinical symptoms.

Detailed Description

Idiopathic nephrotic syndrome is defined as the development of proteinuria, edema, hypoalbuminemia, and hyperlipidemia often presenting in the pediatric population. The underlying pathogenesis of idiopathic nephrotic syndrome is poorly understood but likely involves dysregulation of the immune system, and the majority of patients respond to steroid therapy and other immunosuppressive therapy. Unfortunately, relapses are common, with at least one relapse occurring in up to 90% of patients. Frequently-relapsing patients may be exposed large amounts of steroids and other immunosuppressants with a multitude of adverse effects, while others may not even respond to these treatments. Therefore, novel therapies are being studied.

Vagus nerve stimulation is a novel therapy with the potential to treat inflammatory conditions via inhibition of cytokine release by the cholinergic anti-inflammatory pathway. The purpose of the proposed study is to investigate the use of vagus nerve stimulation in the prevention of nephrotic syndrome relapses and treatment of proteinuria in pediatric patients with idiopathic nephrotic syndrome.

Patients will be enrolled if they have frequently-relapsing idiopathic nephrotic syndrome or proteinuria which does not respond to steroid therapy. These patients will perform daily transcutaneous auricular Vagus Nerve stimulation (taVNS) therapy 5 minutes a day for a 6 month period and will be monitored for urine/bloodwork or clinical signs of nephrotic syndrome relapse.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
7
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Steroid Sensitive Frequently-Relapsing Nephrotic SyndromeTranscutaneous Auricular Vagus Nerve (taVNS) stimulationIndividuals in this arm of the study will have to have a diagnosis of steroid sensitive frequently relapsing idiopathic nephrotic syndrome. They will receive transcutaneous auricular VNS (taVNS) performed for 5minutes every day for 6 months. The settings of the taVNS device will be individualized for each patient. Data will be collected on the the number of nephrotic syndrome relapses, the time between relapses, the time to remission once relapsed, and the level of proteinuria before and while using taVNS therapy.
Steroid Resistant Idiopathic Nephrotic SyndromeTranscutaneous Auricular Vagus Nerve (taVNS) stimulationIndividuals in this arm of the study will have to have a diagnosis of steroid resistant idiopathic nephrotic syndrome. They will receive transcutaneous auricular VNS (taVNS) performed for 5minutes every day for 6 months. The settings of the taVNS device will be individualized for each patient. Data will be collected on the the number of nephrotic syndrome relapses, the time between relapses, the time to remission once relapsed, and level of proteinuria before and while using taVNS therapy.
Primary Outcome Measures
NameTimeMethod
Safety and tolerability of taVNS (Arms 1 and 2)6 months

The endpoint of heart rate monitoring as a measure of safety of taVNS in this population was selected as this is the most concerning adverse effect of taVNS therapy. If there is no heart rate-related events during this study, it would further justify safe use of taVNS in the pediatric population.

Tolerability is an important measure in this study but is mostly a subjective measure. Therefore, patients who withdraw due to intolerability or report side effects which are deemed intolerable will aid in determining the feasibility of taVNS use in this population.

Secondary Outcome Measures
NameTimeMethod
Impact of taVNS on level of proteinuria (Arm 2)6 months

The marker of disease progression and worsening outcomes is the level of proteinuria in patients with steroid-resistant idiopathic nephrotic syndrome. Measurement of the urine protein to creatinine level on a first morning sample is the most feasible and accurate measure of proteinuria in this patient population.

Impact of taVNS on cytokine levels (Arms 1 and 2)6 months

TaVNS has been shown in literature to have an anti-inflammatory effect when stimulating the vagus nerve. Several studies have found that cytokine levels are increased in nephrotic syndrome relapses as compared to levels when in remission. This endpoint provides a measure of the efficacy and compliance of taVNS use while also providing a marker for the effect of taVNS on the patient. Finally, if taVNS is shown to reduce the number of relapses while also suppressing cytokine levels, it may suggest a cytokine-associated etiology of idiopathic nephrotic syndrome.

Impact of taVNS on number of nephrotic syndrome relapses, time to nephrotic syndrome relapses, and time to remission (Arm 1)6 months

This outcome was chosen as an important measure of the efficacy of taVNS on patients with idiopathic nephrotic syndrome. A reduction in the number of relapses suggests that taVNS is a potential therapy for idiopathic nephrotic syndrome.

Trial Locations

Locations (1)

Northwell

🇺🇸

New Hyde Park, New York, United States

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