Ear Stimulation for Ehlers-Danlos Syndrome

Overseen By Katherine Tucker

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Disqualifiers: Pregnancy, Seizures, Autism, 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: Unknown

Duration: 4 weeks

10 Participants Needed

Trial Summary

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

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Transcutaneous Auricular Neurostimulation for Ehlers-Danlos Syndrome?

Research shows that Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) can reduce pain and inflammation in conditions like erosive hand osteoarthritis, suggesting it might help with similar symptoms in Ehlers-Danlos Syndrome. ^{1 2 3 4 5}

Is ear stimulation (taVNS) safe for humans?

Ear stimulation, known as transcutaneous auricular vagus nerve stimulation (taVNS), is generally considered safe for humans. Most studies report only mild and temporary side effects like ear pain, headache, and tingling, with no severe adverse events linked to the treatment. ^{1 6 7 8 9}

How does the treatment Transcutaneous Auricular Neurostimulation differ from other treatments for Ehlers-Danlos Syndrome?

Transcutaneous Auricular Neurostimulation (taVNS) is unique because it is a non-invasive treatment that uses electrical stimulation on the outer ear to activate the vagus nerve, potentially modulating various physiological processes without the need for surgery or medication. This approach is different from traditional treatments as it targets the nervous system directly through the ear, offering a novel way to manage symptoms. ^{1 2 4 5 8}

What is the purpose of this trial?

Hypermobile EDS and hypermobile spectrum disorder (collectively referred to as hEDS) are estimated to affect 1 in 500 individuals worldwide. hEDS patients have limited treatment options for their numerous symptoms that impact the quality of life. This clinical trial tests a new ear stimulation method in hEDS patients to determine if it may improve quality of life.

Research Team

Jeffrey Borckardt, PhD

Principal Investigator

Medical University of South Carolina

Eligibility Criteria

This trial is for individuals aged between 18 and 65 who have been diagnosed with hypermobile Ehlers-Danlos Syndrome (hEDS) or related disorders. They should be experiencing persistent symptoms in at least two areas such as pain, fatigue, sleep issues, anxiety, depression, gastrointestinal function, autonomic or immune function.

Inclusion Criteria

I can read, write, give consent, and follow instructions.

I have been diagnosed with hEDS or HSD and experience persistent symptoms in two or more areas such as pain, fatigue, or sleep.

Exclusion Criteria

I have never had ear trauma or damage.

Not pregnant

Residing in the state of South Carolina

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 4 weeks of at-home, self-administered active Transcutaneous Auricular Neurostimulation (tAN)

4 weeks

Weekly remote assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Remote follow-up assessments

Treatment Details

Interventions

• Transcutaneous Auricular Neurostimulation

Trial Overview The trial is exploring the effectiveness of Transcutaneous Auricular Neurostimulation on improving quality of life for hEDS patients. It's a new ear stimulation method being tested to see if it can alleviate various symptoms associated with hEDS.

Participant Groups

Group I: Four Weeks of Active Transcutaneous Auricular Neurostimulation Experimental Treatment 1 Intervention

Participants will receive 4 weeks of at-home, self-administered active Transcutaneous Auricular Neurostimulation (tAN).

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?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

MUSC Blue Sky initiative

Collaborator

Trials

1

Recruited

10+

Findings from Research

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]

Auricular transcutaneous electrical nerve stimulation (TENS) did not show significant overall effects on pain threshold or autonomic functions in a study of 24 healthy subjects.

Despite the lack of overall significance, some individuals experienced notable increases in pain threshold, with 4 subjects showing over a 50% increase and 6 subjects showing a 30% increase from baseline, suggesting potential variability in response to TENS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of auricular transcutaneous electrical nerve stimulation (TENS) on experimental pain threshold and autonomic function in healthy subjects. Johnson, MI., Hajela, VK., Ashton, CH., et al.[2021]

In an open-label pilot study involving 18 patients with erosive hand osteoarthritis, transcutaneous auricular VNS (taVNS) significantly reduced hand pain by a median of 23.5 mm on a pain scale after 4 weeks, indicating its potential efficacy in managing symptoms.

The study found that taVNS was well-tolerated, with no serious adverse events reported, suggesting it is a safe intervention for patients, although one participant experienced discomfort leading to discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Transcutaneous Vagus Nerve Stimulation in Erosive Hand Osteoarthritis: Results from a Pilot Trial. Courties, A., Deprouw, C., Maheu, E., et al.[2022]

In a study involving 26 subjects, simultaneous stimulation of the cymba and concha (CC) areas of the ear using extra-large electrodes was found to be the most effective for eliciting vagus somatosensory evoked potentials (VSEP), indicating strong neuromodulation effects.

The research demonstrated that the earlobe is not an effective target for taVNS, and using larger electrodes not only increased the amplitude of the response but also made the stimulation more comfortable for participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of different vagus nerve stimulation anatomical targets in the ear by vagus evoked potential responses. de Gurtubay, IG., Bermejo, P., Lopez, M., et al.[2021]

Vagus nerve stimulation (VNS), particularly through non-invasive methods like transcutaneous VNS (tVNS), shows promise for treating various clinical disorders, including heart failure and migraines, by stimulating the auricular branch of the vagus nerve without the need for surgical implantation.

Current research highlights the need for more detailed studies on the neuroanatomy of the auricular branch of the vagus nerve (ABVN) to better understand its therapeutic effects and optimize stimulation parameters, as existing literature lacks consensus on the most effective stimulation sites.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The anatomical basis for transcutaneous auricular vagus nerve stimulation. Butt, MF., Albusoda, A., Farmer, AD., et al.[2022]

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]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive treatment method that applies electrical current to the outer ear to stimulate the vagus nerve, which has been explored for its therapeutic potential in various diseases.

Over the past two decades, taVNS has gained attention as an alternative to drug treatments, but the field also faces limitations that need to be addressed for further development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation: From Concept to Application. Wang, Y., Li, SY., Wang, D., et al.[2022]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

High-resolution computational modeling of the current flow in the outer ear during transcutaneous auricular Vagus Nerve Stimulation (taVNS). [2023]

2. United States pubmed.ncbi.nlm.nih.gov

The effects of auricular transcutaneous electrical nerve stimulation (TENS) on experimental pain threshold and autonomic function in healthy subjects. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of Transcutaneous Vagus Nerve Stimulation in Erosive Hand Osteoarthritis: Results from a Pilot Trial. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Evaluation of different vagus nerve stimulation anatomical targets in the ear by vagus evoked potential responses. [2021]

5. England pubmed.ncbi.nlm.nih.gov

The anatomical basis for transcutaneous auricular vagus nerve stimulation. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices. [2022]

8. Singapore pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation: From Concept to Application. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. [2023]