Transcutaneous Auricular Vagus Nerve Stimulation for Chronic Kidney Disease

Overseen By David Charytan, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: NYU Langone Health

Disqualifiers: Primary ANS disorders, Arrhythmias, Dialysis, Epilepsy, others

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

Compensation: Varies

Number of Visits: 14

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called transcutaneous auricular vagus nerve stimulation (taVNS) for individuals with advanced chronic kidney disease (CKD). Researchers aim to determine if this treatment can safely manage issues related to the autonomic nervous system, which controls functions like heart rate and digestion. Participants will join one of two groups: one receiving the active treatment and the other receiving a sham (inactive) version for comparison. This study suits those diagnosed with CKD at stages 3 to 5 who are receiving care at NYU's Nephrology outpatient clinic. As an unphased trial, it offers a unique opportunity to contribute to groundbreaking research that could enhance CKD management.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that transcutaneous auricular vagus nerve stimulation is safe for chronic kidney disease patients?

Research has shown that using a device to gently stimulate a nerve in the ear, known as transcutaneous auricular vagus nerve stimulation (taVNS), is generally safe and well-tolerated. In past studies, participants experienced benefits with few side effects. For example, taVNS lowered heart rate without significantly affecting blood pressure during stress tests, indicating safety for most individuals. Another study on individuals with chronic insomnia found that taVNS improved sleep without major negative effects. While research on taVNS for chronic kidney disease is still developing, these findings suggest it is a promising and safe treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about transcutaneous auricular vagus nerve stimulation (taVNS) for chronic kidney disease because it offers a non-invasive approach that could potentially modulate the nervous system to improve kidney function. Unlike traditional treatments that often involve medication to manage symptoms or slow disease progression, taVNS works by stimulating the vagus nerve through the skin of the ear, which may help reduce inflammation and improve kidney health. This innovative technique targets the body's nervous system directly, potentially offering a new avenue for treatment with fewer side effects compared to conventional drugs.

What evidence suggests that transcutaneous auricular vagus nerve stimulation is effective for chronic kidney disease?

Research has shown that transcutaneous auricular vagus nerve stimulation (taVNS) might aid kidney problems. In earlier studies, taVNS lowered protein levels in urine, a positive indicator for kidney health. It also reduced inflammation markers like TNF-α, often elevated in individuals with chronic kidney disease (CKD). Additionally, taVNS has been linked to improved brain function by increasing blood flow to the brain. This trial will compare active taVNS with a sham intervention to evaluate its effectiveness for people with CKD. These findings suggest that taVNS could be a beneficial treatment for those with CKD. ^{2 5 6 7 8}

Who Is on the Research Team?

Qandeel Soomro, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

This trial is for individuals with chronic kidney disease stages 3-5. It's designed to see if a non-invasive nerve stimulation technique can help with nervous system issues related to their condition.

Inclusion Criteria

Receiving care at NYU Nephrology outpatient practice

Able to provide informed consent

My kidney function is moderately to severely reduced.

Exclusion Criteria

Presence of a permanent pacemaker

Incarcerated individuals

Pregnant individuals

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either sham or active taVNS for two weeks, with daily 15-minute sessions

2 weeks

14 sessions (daily)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)

Trial Overview The study tests transcutaneous auricular vagus nerve stimulation (taVNS), comparing an active device against a sham (inactive) one in a small group of patients, to assess its safety and effectiveness.

How Is the Trial Designed?

Group I: Active taVNS Experimental Treatment 1 Intervention

Participants receive two weeks of 15-minute taVNS daily in the morning.

Group II: Sham taVNS Placebo Group 1 Intervention

Participants receive two weeks of 15-minute sham intervention daily in the morning.

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

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]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a safe and effective neuromodulation therapy for a variety of conditions, including epilepsy, depression, and anxiety, indicating its broad therapeutic potential.

Despite its effectiveness, there is currently no standardization among taVNS devices, and further research is needed to clarify the relationship between stimulation parameters and therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices. Wang, L., Wang, Y., Wang, Y., et al.[2022]

Transcutaneous auricular Vagus Nerve Stimulation (taVNS) can be optimized by varying electrode designs, which significantly affects the sensitivity and selectivity of nerve activation in different regions of the ear, as shown through a detailed anatomical model and finite element analysis.

The study found that smaller electrodes increase the electric field strength for a given current, allowing for more targeted stimulation of specific ear regions, which is crucial for enhancing the efficacy of taVNS in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-resolution computational modeling of the current flow in the outer ear during transcutaneous auricular Vagus Nerve Stimulation (taVNS). Kreisberg, E., Esmaeilpour, Z., Adair, D., et al.[2023]

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 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) 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]

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) 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) 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]

Noninvasive transcutaneous stimulation of the auricular branch of the vagus nerve (AB-VNS) significantly reduces spontaneous ventricular arrhythmias in beagle dogs after myocardial infarction, indicating its potential as an antiarrhythmic treatment.

AB-VNS enhances ventricular electrical stability and reduces ventricular interstitial fibrosis, although it does not improve overall cardiac function or reverse structural changes in the heart after 4 weeks of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation reduces ventricular arrhythmias and increases ventricular electrical stability. Nasi-Er, BG., Wenhui, Z., HuaXin, S., et al.[2019]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2405844024158720

Transcutaneous auricular vagus nerve stimulation ... taVNS improved cognitive function by increasing cerebral oxygenation, with significant correlations to reaction times and MoCA scores.

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05981183/transcutaneous-auricular-vagus-nerve-stimulation-device-in-ckd-population

Transcutaneous Auricular Vagus Nerve Stimulation Device ... This data will enhance understanding of the short-term safety, tolerability and effects of this novel therapeutic approach in the setting of CKD ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8790887/

Transcutaneous auricular vagus nerve stimulation (taVNS) ... taVNS was associated with clinical remission in FRNS and moderately reduced proteinuria in non-congenital SRNS.

4. clinicaltrials.med.nyu.edu clinicaltrials.med.nyu.edu/clinicaltrial/2202/single-center-pilot-study/

A Single Center Pilot Study on the Use of a Transcutaneous ... This study aims to gather initial data on the potential effectiveness of a transcutaneous auricular vagal nerve stimulation device in patients diagnosed ...

5. journals.lww.com journals.lww.com/jasn/fulltext/2021/10001/transcutaneous_auricular_vagus_nerve_stimulation.1835.aspx

Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)... taVNS prevented NS relapses in FRNS, reduced proteinuria in SRNS, and reduced TNF-α levels without any adverse effects, suggesting taVNS as a promising therapy ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05981183

Transcutaneous Auricular Vagus Nerve Stimulation Device ... The purpose of this pilot interventional study is to collect preliminary data on the application of a transcutaneous auricular vagal nerve stimulation (taVNS) ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12061502/

Effects of Transcutaneous Auricular Vagus Nerve Stimulation ... taVNS can reduce HR with minimal effect on blood pressure by inducing parasympathetic dominance during exercise stress tests.

8. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2828072

Transcutaneous Auricular Vagus Nerve Stimulation for ... This randomized clinical trial investigates the efficacy and safety of transcutaneous auricular vagus nerve stimulation (taVNS) for chronic insomnia.