taVNS for FRNS in Children

NCT05588063 | Recruiting DMC FDA Device

• 2 other identifiers: 22-04881R01DK131091-01A1
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

Children with frequently relapsing nephrotic syndrome (FRNS) are exposed to prolonged courses of steroids and other immunosuppressant medications. Given the adverse side effect profiles and variable efficacy of these medications, there is an urgent need to identify novel and safe therapies to treat nephrotic syndrome in children. Stimulation of the vagus nerve, which can be activated non invasively by transcutaneous auricular vagus nerve stimulation (taVNS), has immunomodulatory effects mediated by the inflammatory reflex and spleen. taVNS has become a therapy of interest for treating chronic immune mediated illnesses. The aims of the study are (1) To determine the feasibility of protocol implementation and tolerability of taVNS in the treatment of nephrotic syndrome in children (2) To establish proof-of-concept and generate statistical estimates of variance parameters and effect sizes for treatment response outcomes in children with nephrotic syndrome randomized to taVNS therapy compared with sham therapy (3) To investigate the effects of taVNS on inflammatory markers in children with nephrotic syndrome.

Conditions

Nephrotic Syndrome in Children; Minimal Change Disease; Focal Segmental Glomerulosclerosis

Keywords

vagus nerve stimulation; pediatric; nephrology

Outcome Measures

Primary Outcomes (1)

• Success of Pilot Trial

  1. Unsuccessful, main study not practicable (1) None of the benchmarks are met, or (2) One or more of the benchmarks are not met and there is low likelihood of reaching benchmarks even with protocol modifications or (3) Serious adverse events related to the treatment. 2. Probable Success main study practicable with modifications to protocol. One or more of the benchmarks are not met, but there is a high likelihood that the benchmark can be met with protocol modifications. 3. Successful main study practicable without modifications. All of the benchmarks are met.

  Baseline through 26 weeks

Secondary Outcomes (14)

• Proof-of-Concept Decision Criteria using relative risk for relapse

  Baseline through 26 weeks

• Estimates of Variance for proportion with nephrotic syndrome relapse

  Baseline through 26 weeks

• Estimates of Variance for time to nephrotic syndrome relapse

  Baseline through 26 weeks

• Estimates of Variance for time to achieve remission once a relapse occurs

  Baseline through 26 weeks

• Recruitment rate

  Baseline through 26 weeks

Study Arms (2)

Intervention Group

EXPERIMENTAL

The intensity setting for pulse amplitude will be adjusted to the participant's tolerance (if a sensation is felt) to a maximum level of 3 on the dial indicator. The remaining settings will be stored in the device and will not need to be set for each treatment. Participants and guardians will be instructed to adjust intensity to highest level of tolerance each time the device is used and level will be logged.

Device: Transcutaneous auricular vagus nerve stimulation

Sham Group

SHAM COMPARATOR

The sham device will be disabled internally so that electrical stimulation is not delivered, but the device will appear to function. Externally, the sham device will look identical to the taVNS device. The participant will be told to increase the intensity until tolerated if a sensation is felt, but will be asked to stop at a maximum level of 3. This inactive sham method was chosen because previous studies have shown that stimulation with placement of the ear clip on other parts of the ear such as the earlobe, although not innervated by the vagus nerve, results in some vagus nerve activity. Inactive sham methodology has been used in previous studies.

Device: Sham device

Interventions

Transcutaneous auricular vagus nerve stimulation DEVICE

The device to be used is the Roscoe Medical TENS 7000, a commercially available handheld electrical pulse generator, and an ear clip to be placed at the left ear for stimulation. Custom-made ear clips with electrode gel will be placed near the entrance to the canal of the ear to provide stimulation to the auricular branch. The handheld electrical pulse generator will be programmed to deliver electrical stimulation pulses to the cymba concha stimulating the auricular branch of the vagus nerve.

Also known as: Roscoe TENS 7000

Intervention Group

Sham device DEVICE

The device will appear to function but no electrical stimulation will be delivered.

Also known as: Roscoe TENS 7000

Sham Group

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• FRNS
• Age 3-17 years
• Glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m2
• Minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS) diagnosis (clinical diagnosis or per biopsy)
• Steroid sensitive nephrotic syndrome (prior history of remission within 4 weeks of steroid therapy)
• In remission at time of enrollment (remission defined as UPC \<0.2 or negative dipstick for 3 consecutive days)
• Informed consent from the parent or guardian and assent from a minor of ≥ 7. years

You may not qualify if:

• Secondary forms of nephrotic syndrome
• SRNS
• Steroid dependent nephrotic syndrome (relapse within 14 days of stopping steroids or relapse while on steroids)
• Exposure to steroids within 14 days of enrollment
• Receiving any standing immunosuppression (previous exposure \> 2 months allowed and/or B cell repletion)
• Any known inflammatory condition (e.g. systemic lupus erythematosis)
• History of cardiac disease (arrhythmias, structural/functional abnormalities)
• Implantable electronic devices
• Pregnancy
• Participants/guardians or participants who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures

Sponsors & Collaborators

• Northwell Health: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (2)

Cohen Children's Medical Center

New Hyde Park, New York, 11040, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19102, United States

RECRUITING

MeSH Terms

Conditions

Nephrosis, Lipoid; Glomerulosclerosis, Focal Segmental

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Christine B Sethna, MD, EdM

CONTACT

718-470-3491; csethna@northwell.edu

Suzanne Vento, RN

CONTACT

718-470-3491; svento@northwell.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The trial will be double blinded to the investigators and participants. Unblinding will occur after all participants have completed the randomization phase of each study trial (Week 26).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2022
• First Posted: October 20, 2022
• Study Start: January 5, 2023
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Within 12 months of study closure

Locations

US (2)