taVNS for Chronic Kidney Disease

Overseen By Qandeel Soomro, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: NYU Langone Health

Must not be taking: Labetalol, Beta blockers

Disqualifiers: Pacemaker, Pregnancy, Epilepsy, Diabetes, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new device called the Transcutaneous Auricular Vagus Nerve Stimulation Device to determine its potential benefits for people with chronic kidney disease (CKD) by stimulating a nerve in the ear. Researchers aim to assess the safety of this method and its effects on heart health in individuals with CKD. The study compares two different levels of nerve stimulation to identify the most effective one. It is suitable for those with CKD at stages 3-5 who are not on dialysis or insulin for diabetes. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance heart health in CKD patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but patients on labetalol cannot participate, and at least 50% of participants must not be on beta blockers.

What prior data suggests that this taVNS device is safe for chronic kidney disease patients?

Research has shown that transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe. In one study, participants tolerated taVNS well, with an average stimulation level of 1.66 mA, and no one stopped treatment due to side effects. The only reported issue was mild skin irritation, which was not serious. This suggests taVNS is safe for most people.

Another study found taVNS to be a safe method for managing pain in individuals with knee osteoarthritis. These findings are promising, indicating that taVNS might be a safe treatment for various conditions. While the safety data appears encouraging, more research is needed to confirm these results in different situations, such as chronic kidney disease. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) treatment for chronic kidney disease because it offers a non-invasive alternative to the current standard, which often involves medications or dialysis. Unlike these traditional methods, taVNS uses a device that stimulates the vagus nerve through the skin of the ear, potentially reducing kidney inflammation and improving function without the need for drugs. The treatment has two variations: one uses a pulse width of 250 μs at 50 Hz, while the other uses 300 μs at 25 Hz, allowing researchers to explore different stimulation settings for optimal kidney health benefits. This approach is unique as it targets the nervous system directly, opening a new avenue for treating chronic kidney disease.

What evidence suggests that this taVNS device is effective for chronic kidney disease?

Research suggests that transcutaneous auricular vagus nerve stimulation (taVNS) might benefit people with chronic kidney disease (CKD). In this trial, participants will receive taVNS in one of two different intervention arms. Studies have found that taVNS can enhance thinking skills by increasing oxygen levels in the brain, which links to faster reaction times. It has also shown improvement in some kidney-related conditions and a decrease in protein levels in urine. These findings indicate potential benefits of taVNS for CKD, but further research is needed to confirm its effectiveness for this condition. ^{1 2 6 7 8}

Who Is on the Research Team?

David Charytan, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with moderate to severe chronic kidney disease (stages 3-5). It's not suitable for those with pacemakers, prisoners, pregnant women, individuals unable to consent, people with certain nervous system disorders like Parkinson's with autonomic dysfunction, recent heart attack survivors, dialysis patients, epilepsy sufferers or diabetics. Also excluded are those on labetalol medication or if over half the group is taking beta blockers.

Exclusion Criteria

I have not had a heart attack in the last 4 weeks.

I have epilepsy.

You rely on a pacemaker to help your heart beat.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Measurement

Participants undergo a 15-minute baseline measurement period before intervention

15 minutes

1 visit (in-person)

Intervention

Participants receive 15 minutes of transcutaneous auricular vagal nerve stimulation (taVNS) with different parameters for Intervention A and B

15 minutes

1 visit (in-person)

Post-Intervention Monitoring

Participants are monitored for changes in heart rate variability and blood pressure for 15 minutes post-intervention

15 minutes

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Transcutaneous Auricular Vagus Nerve Stimulation Device

Trial Overview The study tests a non-invasive ear device that stimulates the vagus nerve using electrical impulses in two different doses. The goal is to see if it's safe and tolerable and whether it could help reduce heart-related deaths in people with chronic kidney disease. This pilot will guide the design of a larger future study.

How Is the Trial Designed?

Group I: Intervention B Experimental Treatment 1 Intervention

Participants will receive 15 minutes of taVNS after an initial 15 minute rest-period and a 15 minute baseline measurement period. For participants assigned to Intervention B, the pulse width = 300 μs, frequency = 25 Hz.

Group II: Intervention A Experimental Treatment 1 Intervention

Participants will receive 15 minutes of taVNS after an initial 15 minute rest-period and a 15 minute baseline measurement period. For participants assigned to Intervention A, the pulse width = 250 μs, and frequency = 50 Hz.

Transcutaneous Auricular Vagus Nerve Stimulation Device is already approved in United States for the following indications:

Approved in United States as taVNS for:

• Epilepsy (not directly related to taVNS but to traditional VNS)
• Refractory depression (not directly related to taVNS but to traditional VNS)
• Chronic obesity (not directly related to taVNS but to traditional VNS)

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Published Research Related to This Trial

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) 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]

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]

In a study involving four patients, a novel technique using parallel and overlapping vein segments successfully extended the length of the venous outflow for transposition arteriovenous fistulas (T-AVFs), allowing for effective vascular access in hemodialysis.

All patients maintained functional T-AVFs for follow-up periods ranging from 4 to 14 months without any complications such as arm swelling, indicating the safety and efficacy of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extending outflow brachial vein length for transposition arteriovenous fistulas. Jennings, WC., Howard, CA., Lee, FS., et al.[2017]

In a study of 141 hemodialysis patients using tunneled central venous catheters (tCVCs), the cumulative survival rate was high, with 91% at 1 year and 85% at 4 years, indicating their effectiveness as a vascular access option.

The main reason for catheter replacement was dysfunction, occurring at a low rate of 0.18 per 1,000 catheter days, and there were relatively few catheter-related bloodstream infections (CRBS), suggesting that tCVCs can be a safe and viable choice for patients with limited access options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodialysis tunneled central venous catheters: five-year outcome analysis. Mandolfo, S., Acconcia, P., Bucci, R., et al.[2017]

The study involved 21 patients undergoing a two-stage procedure to create arteriovenous fistulas between the brachial artery and its transposed venae comitantes, showing a cumulative primary patency rate of 75.89% at 1 year and 55.34% at 2 years.

Despite the promising patency rates, complications occurred in 11 out of 21 fistulas, including thrombosis and infection, indicating that while this technique is a viable alternative for vascular access, careful monitoring for complications is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unusual vascular access for hemodialysis: transposed venae comitante of the brachial artery. Elwakeel, HA., Saad, EM., Elkiran, YM., et al.[2007]

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]

In a study of 138 hemodialysis patients, tunneled central venous catheters (TCVC) were primarily used as a temporary solution while waiting for arteriovenous fistulas (AVF) to mature, with an average lifespan of about 141 days.

While complications occurred in 46% of procedures, most were benign; however, significant risks included infections and thrombosis, particularly in patients with a history of heart disease or low hemoglobin levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tunneled catheters in hemodialysis: Indications and complications. Chouhani, BA., Kabbali, N., Chiba Bennani, S., et al.[2022]

The report introduces a novel technique for creating an autogenous arteriovenous fistula (AVF) using paired brachial veins in patients lacking traditional superficial veins, which is crucial for long-term hemodialysis access.

This innovative approach may broaden the options available for AVF creation, potentially benefiting patients who previously had limited access options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel approach to autogenous hemodialysis access: paired brachial vein transposition in series. Pilla, J., Grisafi, J., George, D.[2023]

Citations

1. 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) ...

2. 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.

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. 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 ...

5. 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7416299/

Effect and Safety of Transcutaneous Auricular Vagus Nerve ... Our study showed that taVNS was safe. Mean stimulation intensity was 1.66 mA, and no patient was required to stop stimulation. Only one skin ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2665913124001122

Safety and preliminary efficacy of transcutaneous auricular ... Our preliminary data demonstrated that tVNS may be a safe pain-relieving treatment for people with knee OA.

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.