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

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new ear stimulation method, Transcutaneous Auricular Neurostimulation, to help people with hypermobile Ehlers-Danlos Syndrome (hEDS) feel better. The goal is to determine if this treatment can improve daily life for those facing constant issues like pain, fatigue, or sleep problems. Participants should have hEDS with ongoing symptoms in at least two areas, such as pain or fatigue, and be able to follow instructions easily. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance the quality of life for hEDS patients.

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 prior data suggests that this ear stimulation method is safe for hEDS patients?

Research has shown that transcutaneous auricular neurostimulation (tAN) is generally safe. This non-invasive method uses a small device to send electrical signals to parts of the ear. Most people experience only mild and short-lived side effects, such as slight tingling or discomfort at the application site. This method has been safely used for various conditions, including epilepsy. While specific information on its use in hypermobile Ehlers-Danlos Syndrome (hEDS) is still being gathered, its application in other areas suggests it is safe. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for Ehlers-Danlos Syndrome, which often focus on managing symptoms with pain medication and physical therapy, Transcutaneous Auricular Neurostimulation (tAN) offers a unique approach by targeting the nervous system directly through the ear. This method involves a non-invasive, at-home, self-administered device that stimulates nerves to potentially reduce pain and improve quality of life. Researchers are excited about tAN because it opens the possibility of a treatment that addresses the root causes of discomfort in Ehlers-Danlos Syndrome, rather than just alleviating the symptoms.

What evidence suggests that this ear stimulation method is effective for hEDS?

Studies have shown that Transcutaneous Auricular Neurostimulation (tAN), a type of ear stimulation, can enhance the function of the heart's vagus nerve, which is crucial for heart health. This improvement might alleviate symptoms like nausea, common in individuals with Hypermobile Ehlers-Danlos Syndrome (hEDS). Some trials have found that this ear stimulation lacks significant side effects. Although research remains in the early stages, stimulating the ear could potentially improve the quality of life for people with hEDS by affecting nerve pathways. Participants in this trial will undergo four weeks of at-home, self-administered active Transcutaneous Auricular Neurostimulation to assess its effects. ^{1 3 6 7 8}

Who Is on the Research Team?

Jeffrey Borckardt, PhD

Principal Investigator

Medical University of South Carolina

Are You a Good Fit for This Trial?

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

Not pregnant

History of documented Autism spectrum disorder (ASD) diagnosis

Residing in the state of South Carolina

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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) 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) 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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06105541

NCT06105541 | Hypermobile Ehlers-Danlos Syndrome Transcutaneous Auricular Neurostimulation (tAN) is a wearable, electrical stimulation device that delivers electricity to specific parts of the human ear. What ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11996051/

Cardiac Vagal Efficiency Is Enhanced by Percutaneous ... Cardiac Vagal Efficiency Is Enhanced by Percutaneous Auricular Neurostimulation in Adolescents With Nausea: Moderation by Antidepressant Drug ...

3. withpower.com withpower.com/trial/transcutaneous-auricular-neuromodulation-for-ehlers-danlos-syndrome-c956c

Transcutaneous Auricular Neuromodulation for Ehlers ... This trial is for individuals with Hypermobile Ehlers-Danlos Syndrome or Hypermobility Spectrum Disorder who experience persistent symptoms in at least two ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1388245724003353

The effects of transcutaneous auricular vagus nerve ... Results. No side effects were reported by any of the participants. Statistical analysis did not show any significant effect of taVNS on SAI.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06548594

Study Details | NCT06548594 | Out of State - tAN hEDS This clinical trial tests a new ear stimulation method in hEDS patients to determine if it may improve quality of life. Detailed Description. The Ehlers-Danlos ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9772204/

Safety of transcutaneous auricular vagus nerve stimulation ... Although the general impression is that taVNS is a safe technique with only mild and transient adverse effects (AEs), human data on safety and ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05212129

Auricular Vagal Nerve Stimulation for Hypermobile Ehlers- ... Also called a data safety and monitoring board, or DSMB. Early Phase 1 ... Auricular Vagal Nerve Stimulation for Hypermobile Ehlers-Danlos Syndrome.

8. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2021.699473/full

Transcranial Auricular Vagus Nerve Stimulation (taVNS) ... Transcutaneous auricular vagus nerve stimulation (taVNS) is a new, non-invasive neuromodulation method. TAVNS is based on electrical stimulation of cutaneously ...