taVNS for FRNS in Children
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age3-17
SponsorNorthwell Health
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Transcutaneous auricular vagus nerve stimulation
DeviceThe 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.
Sham device
DeviceThe device will appear to function but no electrical stimulation will be delivered.
Treatment groups
30 Participants
are divided into 2 treatment groupsGroup A: Intervention GroupExperimental treatment 1 intervention
Group B: Sham GroupSham comparator 1 intervention
Trial outcomes
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.
Time frame
Baseline through 26 weeksSecondary outcomes
1
Proof-of-Concept Decision Criteria using relative risk for relapse
The decision to move forward with a larger trial will be made based on pre-determined proof of concept decision criteria. Once data from the pilot trial is observed and collected, 1,000 bootstrap resamples with replacement will be carried out to construct the empirical 95% confidence interval (CI) for the relative risk. Using a non-parametric approach, the lower 2.5th percentile and upper 97.5th percentile will be used to construct the CI, and a GO or NO GO decision to conduct the larger scale trial will be made based on a primary end point. The primary end-point is no relapses within 26 weeks. Based on previous literature, it is presumed that 50% in the intervention arm and 25% of those in sham therapy will reach the primary end-point in each trial, which is equivalent to a relative risk of 2.0.
Time frame
Baseline through 26 weeks2
Estimates of Variance for proportion with nephrotic syndrome relapse
Frequency counts and proportions with 95 percent confidence intervals
Time frame
Baseline through 26 weeks3
Estimates of Variance for time to nephrotic syndrome relapse
Mean and standard deviation
Time frame
Baseline through 26 weeks4
Estimates of Variance for time to achieve remission once a relapse occurs
Mean and standard deviation
Time frame
Baseline through 26 weeksSponsors and contacts
Click on the lead sponsor to view all of their trials.
Northwell Health
Lead sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborator
Source ClinicalTrials.gov