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

NCT04169776 | Completed FDA Device

• 1 other identifier: 19-0861
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Idiopathic Nephrotic Syndrome; Frequently Relapsing Nephrotic Syndrome

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of taVNS (Arms 1 and 2)

  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.

  6 months

Secondary Outcomes (3)

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

  6 months

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

  6 months

• Impact of taVNS on level of proteinuria (Arm 2)

  6 months

Study Arms (2)

Steroid Sensitive Frequently-Relapsing Nephrotic Syndrome

EXPERIMENTAL

Individuals 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.

Device: Transcutaneous Auricular Vagus Nerve (taVNS) stimulation

Steroid Resistant Idiopathic Nephrotic Syndrome

EXPERIMENTAL

Individuals 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.

Device: Transcutaneous Auricular Vagus Nerve (taVNS) stimulation

Interventions

Transcutaneous Auricular Vagus Nerve (taVNS) stimulation DEVICE

Participants in this study will perform home transcutaneous auricular vagus nerve stimulation (taVNS) for 5 minutes a day for a 6-month period. The device that will be used is the commercially available Roscoe Medical TENS 7000 vagus nerve stimulator. The device will be attached to the Cymba Concha of the ear via an electrode ear clip. The intensity of the stimulation will be slowly increased and adjusted to individual tolerability for each treatment. TaVNS will be performed for 5 minutes daily for a period of 6 months.

Steroid Resistant Idiopathic Nephrotic Syndrome; Steroid Sensitive Frequently-Relapsing Nephrotic Syndrome

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subjects age 2-21 years of age
• eGFR \> 60 ml/min/1.73 m2
• Diagnosis of idiopathic minimal change disease (clinical diagnosis or per biopsy)
• Prior history of remission of nephrotic syndrome within 4 weeks of initiation of steroid therapy (steroid sensitive nephrotic syndrome)
• or more episodes of nephrotic syndrome relapses in a 6-month period or four or more episodes of nephrotic syndrome relapses in a 12-month period (relapse defined as 2+ proteinuria on first morning urine sample for three consecutive days or development of edema)
• In remission (no proteinuria - normal urine protein to creatinine ratio \< 0.2) at the time of enrollment
• Subjects age 2-21 years of age
• eGFR \> 60 ml/min/1.73 m2
• Diagnosis idiopathic nephrotic syndrome (clinical diagnosis or per biopsy)
• Diagnosis of steroid-resistant nephrotic syndrome (symptoms or proteinuria not improved after 4 to 8 weeks of steroid therapy)
• Persistent proteinuria (first-morning urine protein to creatinine ratio \> 0.2)
• At least 7 days since last dose of steroids

You may not qualify if:

• Subjects with nephrotic syndrome etiology other than idiopathic minimal change disease either biopsy-proven or by genetic testing
• Nephrotic syndrome due to secondary causes such as SLE, vasculitis, hepatitis, post-infectious etiology, medication-induced, etc.
• Subjects that did not achieve remission of nephrotic syndrome within 4 weeks of initiation of steroid therapy (steroid-resistant nephrotic syndrome)
• Subjects with urine protein to creatinine ratio of \> 0.2 (not in remission)
• Subjects currently receiving any standing immunosuppressive therapy (mycophenolate mofetil, tacrolimus, rituximab - note: 1) previous exposure to these therapies does not exclude participation; 2) subjects with previous exposure to rituximab are eligible if B cells are replete)
• Subjects with a history of cardiac issues, including bradycardia, arrhythmias or structural abnormalities of the heart
• Subjects with implantable electronic devices such as pacemakers, defibrillators, hearing aids, cochlear implants or deep brain stimulators
• Subjects with any other known inflammatory condition (IBD, SLE, etc.)
• Nephrotic syndrome due to secondary causes such as SLE, vasculitis, hepatitis, post-infectious etiology, medication-induced, etc.
• Subjects with a history of cardiac issues, including bradycardia, arrhythmias or structural abnormalities of the heart
• Subjects with implantable electronic devices such as pacemakers, defibrillators, hearing aids, cochlear implants or deep brain stimulators
• Subjects with any other known inflammatory condition (IBD, SLE, etc.)

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

Northwell

New Hyde Park, New York, 11040, United States

Location

Related Publications (1)

• Merchant K, Zanos S, Datta-Chaudhuri T, Deutschman CS, Sethna CB. Transcutaneous auricular vagus nerve stimulation (taVNS) for the treatment of pediatric nephrotic syndrome: a pilot study. Bioelectron Med. 2022 Jan 26;8(1):1. doi: 10.1186/s42234-021-00084-6.

  PMID: 35078538 DERIVED

MeSH Terms

Conditions

Nephrosis, Lipoid; Nephrotic Syndrome

Condition Hierarchy (Ancestors)

Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Christine Sethna, MD

  Northwell Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This study design was chosen as it is the most realistic and practical design for this pilot study. There is no blinding or masking in this pilot study.
• Purpose: DEVICE FEASIBILITY
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is a prospective cohort pilot study not formally classified as a specific trial phase. The study will involve two Arms, with 15 participants in each Arm of the study. Arm 1 will recruit patients with steroid-sensitive frequently-relapsing idiopathic nephrotic syndrome. Arm 2 will recruit patients with steroid-resistant idiopathic nephrotic syndrome. All participants in both Arms of the study will perform daily transcutaneous auricular vagus nerve stimulation (taVNS) therapy for 5 minutes each day. The study period will be 6 months. The participants will be monitored for labwork and clinical evidence of nephrotic syndrome relapse, comparing the number of relapses and level or proteinuria in the 6 months before starting taVNS therapy to number of relapses and level of proteinuria in the 6 month study period.

Study Record Dates

• First Submitted: November 15, 2019
• First Posted: November 20, 2019
• Study Start: December 1, 2019
• Primary Completion: March 1, 2021
• Study Completion: December 1, 2021
• Last Updated: September 28, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, ANALYTIC CODE
• Time Frame: 12/1/22 - ongoing
• Access Criteria: Contact PI for data.

Locations

US (1)