Vagus Nerve Stimulation for Nephrotic Syndrome

(kidNEY-VNS Trial)

Recruiting at 1 trial location

Overseen By Suzanne Vento, RN

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Northwell Health

Must be taking: Immunosuppressants, ACE inhibitors

Disqualifiers: Genetic defects, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 20

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for steroid-resistant nephrotic syndrome in children using transcutaneous auricular vagus nerve stimulation (taVNS). This technique uses a small device to send gentle electrical pulses to the vagus nerve through the skin, potentially helping to control inflammation linked to the condition. The trial will compare the effects of this treatment to a similar device that does not deliver stimulation. Children who have not improved after taking steroids for at least four weeks and are on stable treatment plans might find this trial suitable. As an unphased trial, it offers a unique opportunity for children to potentially benefit from an innovative treatment approach.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should have a stable immunosuppression and ACE inhibitor/angiotensin receptor blocker treatment regimen for at least three months, which suggests you may need to continue your current medications.

What prior data suggests that this vagus nerve stimulation technique is safe for children with nephrotic syndrome?

Studies have shown that using a device on the ear to stimulate a nerve, known as transcutaneous auricular vagus nerve stimulation (taVNS), is generally safe. Research indicates that any side effects are mild and resolve quickly. For instance, some individuals might experience a tingling sensation, but it typically doesn't last long. Specific reports of serious side effects directly linked to taVNS have not emerged. This makes it a promising option for treating long-term immune-related issues, such as nephrotic syndrome in children. It's important to consider all options and consult a healthcare provider to determine if this treatment might be suitable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for nephrotic syndrome focus on managing symptoms with medications like corticosteroids and immunosuppressants. But transcutaneous auricular Vagus Nerve Stimulation (taVNS) offers a unique approach by using electrical stimulation to target the vagus nerve, potentially reducing inflammation and improving kidney function without traditional drugs. Researchers are excited because this method could offer a non-invasive, drug-free alternative that minimizes side effects and targets the condition in a novel way.

What evidence suggests that taVNS is effective for nephrotic syndrome?

Research has shown that transcutaneous auricular vagus nerve stimulation (taVNS), a treatment participants in this trial may receive, can help treat nephrotic syndrome, particularly when steroids are ineffective. Studies have found that taVNS can induce remission and lower protein levels in urine, indicating improvement. It also correlates with fewer relapses of the condition. Additionally, taVNS reduces levels of TNF-α, a marker of inflammation, which might aid in managing this condition. These findings suggest taVNS could be a safe and effective option for children with nephrotic syndrome. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for children aged 3-17 with steroid-resistant nephrotic syndrome, specifically those diagnosed with MCD or FSGS via biopsy. Participants must have stable medication regimens and no history of cardiac disease, skin issues at the stimulation site, secondary causes of nephrotic syndrome like genetic conditions, or any implantable electronic devices.

Inclusion Criteria

My B cells have returned to normal after rituximab treatment.

I am between 3 and 17 years old.

My immunosuppression and blood pressure medication have been stable for 3 months.

Exclusion Criteria

I have a known inflammatory condition.

My kidney condition improves with steroid treatment.

Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 8 weeks

1 visit (in-person)

Randomized Control Period

Participants are randomized to either taVNS or sham treatment and use the intervention device for 5 minutes per day for 26 weeks

26 weeks

3 visits (in-person), 3 visits (virtual)

Follow-up

Participants are monitored for clinical status and safety for an additional 26 weeks

26 weeks

Every 8 weeks (in-person or virtual)

Open-label extension (optional)

Participants may opt into continuation of active taVNS treatment after the randomized period

Long-term

Every 8 weeks (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Sham device
• taVNS

Trial Overview

The study tests transcutaneous auricular vagus nerve stimulation (taVNS) against a sham device to see if it's a feasible and tolerable treatment for children's nephrotic syndrome. It also aims to understand taVNS's effects on inflammatory markers in these patients.

How Is the Trial Designed?

Group I: Intervention Group Experimental Treatment 1 Intervention

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.

Group II: Sham Group Placebo Group 1 Intervention

The sham device will be altered 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.

taVNS is already approved in United States, European Union for the following indications:

Approved in United States as Transcutaneous Auricular Vagus Nerve Stimulation for:

• Epilepsy
• Depression
• Obesity

Approved in European Union as Transcutaneous Auricular Vagus Nerve Stimulation for:

• Epilepsy
• Depression

Who Is Running the Clinical Trial?

Northwell Health

Lead Sponsor

Trials

481

Recruited

470,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

This study will investigate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on 15 patients with a minimally conscious state, using five different frequencies (1, 10, 25, 50, and 100 Hz) to determine the optimal stimulation parameters.

The goal is to achieve stable improvements in consciousness levels in patients with disorders of consciousness by optimizing the taVNS neuromodulation technique, with results measured through the coma recovery scale-revised (CRS-R) and resting EEG assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the modulation paradigm of transcutaneous auricular vagus nerve stimulation in patients with disorders of consciousness: A prospective exploratory pilot study protocol. Zhai, W., Jiao, H., Zhuang, Y., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (TaVNS) effectively normalized gastric dysrhythmias in healthy individuals during a water-load test, indicating its potential as a treatment for gastric symptoms.

The study found that TaVNS at 40 Hz improved heart rate variability and reduced bloating, suggesting it positively influences both parasympathetic and sympathetic nervous system pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping. Du, P., Maharjan, A., Calder, S., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) significantly improves depression symptoms, as evidenced by reduced scores on the Hamilton Depression Scale in a review of 12 studies involving 838 participants.

taVNS shows comparable response rates to traditional antidepressants and has fewer side effects, suggesting it could be a safe alternative or complementary treatment for depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of transcutaneous auricular vagus nerve stimulation in the treatment of depressive disorder: A systematic review and meta-analysis of randomized controlled trials. Tan, C., Qiao, M., Ma, Y., et al.[2023]

This case series study of 5 patients with nephrotic syndrome (NS) revealed that NS can be a significant cause of cerebral venous sinus thrombosis (CVST), with all patients initially presenting with headaches and diagnosed via magnetic resonance venography.

All patients in the study fully recovered from CVST after treatment, with no relapses reported during a follow-up period averaging 26.6 months, highlighting the effectiveness of standard CVST treatment in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nephrotic Syndrome May Be One of the Important Etiologies of Cerebral Venous Sinus Thrombosis. Wang, Y., Meng, R., Duan, J., et al.[2017]

Adult idiopathic nephrotic syndrome is primarily caused by the loss of plasma proteins in urine, leading to symptoms like low albumin levels, high cholesterol, and swelling, with four main subclasses requiring specific diagnosis through kidney biopsy.

Treatment varies by subclass and may include corticosteroids, cytotoxic agents, and dietary changes, with management focusing on reducing proteinuria and addressing complications like fluid imbalance and high cholesterol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacologic management of adult idiopathic nephrotic syndrome. Alaniz, C., Brosius, FC., Palmieri, J.[2013]

A study of 26 children with minimal change nephrotic syndrome (MCNS) found that their hearing status remained stable during both remission and relapse periods, with no significant changes in pure tone averages or tympanometry results.

The majority of patients exhibited normal tympanometry results (type A) in both periods, indicating that MCNS does not appear to affect hearing in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of the relapse and remission periods on hearing status in children with minimal change nephrotic syndrome. Bayazit, YA., Balat, A., Pakir, HI., et al.[2006]

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe, with a low incidence of mild and transient adverse effects, such as ear pain, headache, and tingling, reported in only 24.86% of the studies analyzed.

In a systematic review of 177 studies involving 6322 subjects, there was no significant difference in the risk of adverse events between taVNS and control groups, indicating that taVNS is a feasible option for clinical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Kim, AY., Marduy, A., de Melo, PS., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive and cost-effective method for modulating the vagus nerve, making it a promising alternative to traditional surgical vagus nerve stimulation.

taVNS allows for easy and safe administration, with considerations for proper electrode placement and individual dosing based on perception thresholds, which enhances its potential for treating various central and peripheral diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. Badran, BW., Yu, AB., Adair, D., et al.[2020]

A 3-year-old child with steroid-dependent nephrotic syndrome developed a rare case of cerebral vessel thrombosis, specifically superior sagittal sinus thrombosis, presenting with drowsiness and left hemiparesis.

The child fully recovered after treatment with low molecular weight heparin (LMWH), suggesting that LMWH may be effective for preventing or treating thrombosis in nephrotic syndrome, although further controlled studies are needed to confirm its safety and efficacy in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Superior sagittal sinus thrombosis and nephrotic syndrome: favorable outcome with low molecular weight heparin]. de Saint-Martin, A., Terzic, J., Christmann, D., et al.[2019]

A 32-month-old boy with steroid-sensitive nephrotic syndrome (SSNS) developed steroid-resistant nephrotic syndrome (SRNS) and cerebral venous sinus thrombosis (CVST), a rare complication, highlighting the serious risks associated with nephrotic syndrome.

The combination of pulse methylprednisolone, IV Rituximab, and Enoxaparin led to significant improvement in the child's condition, demonstrating an effective treatment strategy for this complex case.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Methylprednisolone Pulse Therapy plus Rituximab for Treating a Rare Juvenile Steroid-Resistant Nephrotic Syndrome with Cerebral Venous Sinus Thrombosis: A Case Report. Sakr, HI., Edrees, B., Taher, HO., et al.[2022]

Transcutaneous vagus nerve stimulation (tVNS) significantly reduced postural tachycardia in patients with POTS, showing a mean heart rate increase of 17.6 beats/min in the active group compared to 31.7 beats/min in the sham group after 2 months.

tVNS also led to lower levels of antiadrenergic autoantibodies and inflammatory cytokines, along with improved heart rate variability, indicating its potential as a safe and effective noninvasive treatment for POTS without any reported side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive Vagus Nerve Stimulation in Postural Tachycardia Syndrome: A Randomized Clinical Trial. Stavrakis, S., Chakraborty, P., Farhat, K., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) using specific parameters (500μs pulse width at 10Hz and 25Hz) was found to significantly decrease heart rate (HR) in healthy individuals, indicating its potential efficacy in modulating HR.

The study demonstrated that taVNS is safe, with no adverse effects reported, and it effectively attenuated sympathetic HR rebound after stimulation, suggesting a beneficial impact on autonomic regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short trains of transcutaneous auricular vagus nerve stimulation (taVNS) have parameter-specific effects on heart rate. Badran, BW., Mithoefer, OJ., Summer, CE., et al.[2020]

A systematic review of 261 studies revealed significant confusion in the nomenclature for transcutaneous stimulation of the auricular branch of the vagus nerve (ABVN), with 67 full and 27 abbreviated terms identified, highlighting the need for standardization.

The most commonly used terms were 'transcutaneous vagus nerve stimulation' and 'tVNS', but there was no consistent one-to-one relationship between full and abbreviated names, indicating a lack of uniformity in terminology across different research teams.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toward Diverse or Standardized: A Systematic Review Identifying Transcutaneous Stimulation of Auricular Branch of the Vagus Nerve in Nomenclature. Wang, Y., Li, L., Li, S., et al.[2023]

Transcutaneous electrical stimulation of the auricular branch of the vagus nerve (taVNS) was found to improve heart rate variability in heart failure patients, indicating a better balance in the autonomic nervous system, with significant improvements in rMSSD and SDNN measurements.

The study, involving 43 patients in a double-blind, randomized design, suggests that taVNS is a safe and well-tolerated intervention that may offer therapeutic benefits for heart failure, although further research with larger sample sizes is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Auricular Vagal Neuromodulation and its Application in Patients with Heart Failure and Reduced Ejection Fraction. Couceiro, SM., Sant'Anna, LB., Sant'Anna, MB., et al.[2023]

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