Neurostimulation Therapy for Reducing Blood Loss

Overseen By David Sailors, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Surgical Vascular

Must not be taking: Platelet inhibitors

Disqualifiers: BMI ≥ 40, Epilepsy, Neurological diseases, Pregnancy, 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: 2

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether transcutaneous auricular neurostimulation (tAN) can reduce blood loss during dialysis port placement procedures. Participants will receive either actual tAN therapy or a sham version to determine any differences in blood loss. This study may suit individuals planning to have a dialysis port placed using a synthetic graft and who do not have conditions such as epilepsy or neurological diseases. As an unphased trial, it offers a unique opportunity to contribute to innovative research that could enhance surgical outcomes.

Will I have to stop taking my current medications?

If you are currently taking a platelet inhibitor medication, you will not be able to participate in the trial. The protocol does not specify about other medications, so it's best to discuss your current medications with the study team.

What prior data suggests that Transcutaneous Auricular Neurostimulation is safe for reducing blood loss during dialysis AV graft placement?

Research has shown that Transcutaneous Auricular Neurostimulation (tAN) is generally safe. Past studies have used tAN to reduce blood loss and treat conditions like tinnitus and insomnia. These studies found that participants tolerated it well, with no major side effects. For instance, tAN was safely used in women with heavy menstrual bleeding, reducing blood loss without harm. Additionally, early research suggests that tAN targets a specific area and does not affect the whole body. This safety record makes tAN a promising option for potential trial participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about transcutaneous auricular neurostimulation (tAN) therapy because it offers a novel way to potentially reduce blood loss during medical procedures, like dialysis port placement. Unlike standard treatments that might involve medications or physical interventions to control bleeding, tAN is a non-invasive technique that uses electrical stimulation through an earpiece to influence the nervous system. This approach could provide a new, drug-free method to enhance patient outcomes with minimal side effects. If successful, tAN could revolutionize how we manage blood loss, offering a quick and effective option where traditional methods might fall short.

What evidence suggests that Transcutaneous Auricular Neurostimulation is effective for reducing blood loss during dialysis AV graft placement?

This trial will compare the effects of active transcutaneous auricular neurostimulation (tAN) with a sham procedure. Research has shown that tAN can help reduce blood loss. In animal studies, similar nerve stimulation reduced bleeding times and blood loss by 45–75% during soft tissue injuries. These results suggest that tAN might also help control blood loss in people. Although more research is needed for specific procedures like placing a dialysis port, these findings are promising for reducing bleeding. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals undergoing dialysis AV graft placement procedures. Specific eligibility criteria are not provided, but typically participants would need to meet certain health standards and not have conditions that could interfere with the study or increase risk.

Inclusion Criteria

I can understand and agree to the study's requirements.

Participant is English proficient

I am getting a dialysis port with a synthetic graft.

Exclusion Criteria

My BMI is 40 or higher.

I am currently on medication to prevent blood clots.

I have an ear infection or my ear shape is unusual.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive 30 minutes of active or sham tAN therapy immediately prior to the dialysis port placement procedure

1 day

1 visit (in-person)

Procedure

Dialysis AV graft placement procedure with monitoring of blood loss and blood markers

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the procedure

4 hours

What Are the Treatments Tested in This Trial?

Interventions

• Transcutaneous Auricular Neurostimulation

Trial Overview

The study is testing whether tAN therapy using the Volta tAN System can reduce blood loss during AV graft placement compared to a SHAM (placebo-like) device. Participants will be randomly assigned to receive either the actual tAN therapy or a non-functional sham treatment.

How Is the Trial Designed?

Group I: Active tAN + standard of care Experimental Treatment 1 Intervention

Participants randomized to the active group will have an earpiece applied and receive 30 minutes of active tAN therapy immediately prior to the dialysis port placement procedure. When the 30-minute tAN session is complete, the system will be turned off, unplugged, and the earpiece will be removed.

Group II: Sham tAN + standard of care Placebo Group 1 Intervention

Participants randomized to the sham group will have an earpiece applied, but stimulation will not be turned on. These participants will receive 30 minutes of sham tAN therapy immediately prior to the dialysis port placement procedure. When the 30-minute tAN session is complete, the system will be turned off, unplugged, and the earpiece will be removed.

Transcutaneous Auricular Neurostimulation is already approved in United States, European Union for the following indications:

Approved in United States as Transcutaneous Auricular Neurostimulation for:

• Chronic pain
• Opioid withdrawal
• Irritable bowel syndrome

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

• Chronic pain
• Temporomandibular disorders

Who Is Running the Clinical Trial?

University Surgical Vascular

Lead Sponsor

Trials

1

Recruited

40+

Spark Biomedical, Inc.

Industry Sponsor

Trials

14

Recruited

560+

Published Research Related to This Trial

The study demonstrates that millimeter wave (MMW) stimulation can selectively activate the auricular branch of the vagus nerve (ABVN) without affecting nearby non-vagal nerves, as shown by significant increases in local field potential (LFP) power in the nucleus tractus solitarii (NTS) during targeted stimulation.

In contrast, non-vagal nerve stimulation resulted in decreased LFP power, indicating that MMW can effectively differentiate between vagal and non-vagal responses, paving the way for a new clinical treatment approach for conditions like depression and epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility study on transcutaneous auricular vagus nerve stimulation using millimeter waves. Song, HY., Shin, DW., Jung, SM., et al.[2022]

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]

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]

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]

In a study involving 17 healthy adults, transcutaneous auricular vagus nerve stimulation (taVNS) at the left tragus significantly increased brain activity in areas associated with the vagal pathway, indicating its potential efficacy in neuromodulation.

Compared to control stimulation at the earlobe, tragus stimulation resulted in greater activation in key brain regions, suggesting that taVNS could be a promising therapeutic approach for influencing brain function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurophysiologic effects of transcutaneous auricular vagus nerve stimulation (taVNS) via electrical stimulation of the tragus: A concurrent taVNS/fMRI study and review. Badran, BW., Dowdle, LT., Mithoefer, OJ., 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 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]

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]

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) effectively increases heart rate variability (HRV), indicating a shift towards parasympathetic dominance, with the most significant effects observed at the cymba conchae and fossa triangularis targets.

The study found that HRV increases in a charge-dependent manner, with optimal stimulation parameters being bursts of taVNS at a pulse duration of 100 μs and a current intensity of 2 mA, suggesting these parameters are both comfortable and effective for enhancing HRV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulation and heart rate variability: Analysis of parameters and targets. Machetanz, K., Berelidze, L., Guggenberger, R., et al.[2021]

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tAN is placed on and around the ear to non-invasively stimulate branches of the vagus and trigeminal nerves and modulate specific brain regions associated with ...

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revealed that VNS is beneficial for tinnitus patients and is safe and practicable when combined with tones that exclude the tinnitus-matched ...