A Pilot Trial of taVNS for SRNS in Children (kidNEY-VNS)

A parallel, double blinded, randomized placebo controlled trial comparing daily taVNS use with sham therapy will be conducted in children 3 to 17 years of age with SRNS. Ten participants with SRNS, defined as lack of response to steroids after 4 weeks, will be randomized 1 to 1 to taVNS or sham therapy. Participants will be enrolled at two pediatric tertiary hospitals over a two year time period, with completion of the study by year three. All participants will perform daily taVNS therapy (active for taVNS arm or inactive for sham arm) for 5 minutes each day for a total of 26 weeks.

Participants will monitor heart rate with each treatment and log home urine results. Participants will be monitored monthly with in person study visits at Weeks 8, 16 and 26 alternating with virtual telehealth visits at Weeks 4, 12 and 20. Biosample specimens will be collected at baseline, 8 weeks, 16 weeks and 26 weeks. There will be a follow up period of an additional 26 weeks. All participants will be given the option to receive the active taVNS treatment at the end of the randomized period.

Study Phases The study will consist of three parts. Part 1 - Screening Period- up to 8 weeks. Informed consent/assent will be obtained at screening prior to the conduct of any study-related procedures. Participants will be screened to confirm inclusion/exclusion criteria are met. Participants must be off steroid treatment for 14 days prior to Day 1 and the participant must be in remission (negative UPC on first morning urine) on Day 1.

Part 2 - Randomized Control Period - 26 weeks: Thirty participants with FRNS who meet all of the eligibility criteria will be randomized 1:1 to either taVNS or sham treatment. A trainer will instruct the parent/guardian on use of the device at the randomization visit. Participants will use the intervention device as directed for 5 minutes per day for 26 weeks. Participants will be monitored monthly with in-person study visits at Weeks 8, 16 and 26 alternating with virtual remote video visits at Weeks 4, 12 and 20. The visit window will be +/- 7 days. At each in person visit, we will conduct:

* Vital signs and physical examination * Assessment for nephrotic syndrome relapses. Home urine protein logs will be reviewed. * Blood and urine samples will be collected at each in person visit. * Assessment of study intervention adherence. Parents/guardians will meet with the trainer and will be reoriented on taVNS device use at each visit as a safety measure. The device counter number will be recorded as a measure of adherence. * Monitor for adverse events and tolerability: Parents/guardians will share a study log with investigators, which describes daily taVNS use, side effects, and any changes in heart rate.

At each virtual remote video visit, we will observe the participant while doing the intervention procedure, assess for nephrotic syndrome relapses, and monitor for any adverse events.

Part 3 - Follow Up Period - 26 weeks: At the completion of the randomized period, participants will be followed for an additional 26 weeks to assess clinical status. For those who stop the intervention, study visits will occur in-person during regularly scheduled clinical visits or via telehealth visit every 8 weeks, whichever is sooner. Participants will be assessed for the number of nephrotic syndrome relapses and home urine protein logs will be reviewed. First morning UPC will be recorded. All participants will be given the option to receive the active taVNS treatment at the end of the randomized period. Unblinding of treatment assignment from the randomized phase will not occur prior to consent for open-label use. As open-label extension trials may introduce significant bias, data obtained from these participants will not be considered part of this research and no statistical analysis will be carried out. However, clinical status and safety will continue to be monitored. In person study visits will occur every 8 weeks for those continuing use of taVNS.

• Effect size for change in Change in quality of life (PedsQL) [Срок оценки: Baseline to 26 weeks]
• Effect size for change in urine protein:creatinine [Срок оценки: Baseline to 26 weeks]
• Effect size for change in lipid profile [Срок оценки: Baseline to 26 weeks]
• Effect size for change in proportion with at least a 30 percent reduction in UPC [Срок оценки: Baseline to 26 weeks]
• Recruitment rate [Срок оценки: Baseline to 26 weeks]
• Rate of completion of study [Срок оценки: Baseline to 26 weeks]
• Successful double-blinding [Срок оценки: Baseline to 26 weeks]
• Treatment adherence from home logs [Срок оценки: Baseline to 26 weeks]
• Adverse events [Срок оценки: Baseline to 26 weeks]
• Incidence of withdrawal due to adverse events [Срок оценки: Baseline to 26 weeks]
• Proof of Concept Decision Criteria [Срок оценки: Baseline to 26 weeks]
• Cytokines [Срок оценки: Baseline to 26 weeks]