Transcutaneous Auricular Neuromodulation for Ehlers-Danlos Syndrome

(hEDS-tAN Trial)

Overseen By Katherine Tucker

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Disqualifiers: Pregnant, Seizures, Ear trauma, others

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

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called transcutaneous auricular neuromodulation, which gently stimulates the ear to see if it can improve symptoms for people with hypermobile Ehlers-Danlos Syndrome (hEDS) or Hypermobile Spectrum Disorder. Researchers aim to determine if this treatment can reduce issues such as pain, fatigue, sleep problems, and anxiety. Participants will receive either a real or placebo version of the treatment at home to compare effects. This trial is open to those diagnosed with hEDS or HSD who experience at least two symptoms, such as pain or sleep issues. As an unphased trial, it offers a unique opportunity to explore innovative treatment options for symptom relief.

Do I need to stop my current medications for this trial?

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

What prior data suggests that transcutaneous auricular neuromodulation is safe for Ehlers-Danlos Syndrome patients?

Research has shown that transcutaneous auricular neuromodulation (tAN), a device that sends small electrical signals to certain parts of the ear, is generally well-tolerated. In earlier studies, participants reported no side effects from using the device, suggesting its safety. The absence of side effects in these studies indicates a positive safety profile. Although this treatment remains under study, current evidence suggests that tAN is likely a safe option for prospective trial participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Transcutaneous Auricular Neuromodulation (tAN) for Ehlers-Danlos Syndrome because it offers a novel, non-invasive approach that targets the nervous system through the ear. Unlike typical treatments that may involve medications addressing symptoms like pain or instability, tAN directly stimulates the auricular branch of the vagus nerve, which could modulate pain and inflammation pathways more effectively. This method stands out because it can be self-administered at home, potentially increasing convenience and adherence compared to current options that often require clinical settings.

What evidence suggests that transcutaneous auricular neuromodulation is effective for Ehlers-Danlos Syndrome?

This trial will evaluate the effects of transcutaneous auricular neurostimulation (tAN) for Ehlers-Danlos Syndrome. Studies have shown that tAN might alleviate various symptoms by sending electrical signals to specific parts of the ear. Research suggests that tAN can improve heart functions, potentially aiding some symptoms of hypermobile Ehlers-Danlos Syndrome (hEDS). Although direct evidence for hEDS remains limited, tAN has been found to boost activity in a nerve that can help manage pain, anxiety, and other symptoms. Overall, this treatment shows promise, but more research is needed to confirm its effectiveness specifically for hEDS. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for individuals with Hypermobile Ehlers-Danlos Syndrome or Hypermobility Spectrum Disorder who experience persistent symptoms in at least two areas such as pain, fatigue, sleep issues, anxiety, depression, and more. Participants must be able to read and write and follow instructions. Those with MRI-unsafe implants, seizure history or ear trauma are excluded.

Inclusion Criteria

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

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

Exclusion Criteria

You have a medical device in your body that makes it unsafe for you to have an MRI.

I have a history of seizures.

Pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Intervention

Participants receive either active or sham transcutaneous auricular neurostimulation (tAN) for 2 weeks

2 weeks

At-home, self-administered

Open-label Phase

All participants receive active transcutaneous auricular neurostimulation (tAN) for 2 weeks

2 weeks

At-home, self-administered

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Transcutaneous Auricular Neuromodulation

Trial Overview The study tests if using a device for transcutaneous auricular neurostimulation at home can improve physical and psychological symptoms of hEDS/HSD patients. It's a randomized trial where half the participants will receive a sham (fake) treatment to compare results.

How Is the Trial Designed?

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

Participants will be randomized to receive 2 weeks of at-home, self-administered active Transcutaneous Auricular Neurostimulation (tAN), followed by 2 additional weeks of at-home, self-administered active Transcutaneous Auricular Neurostimulation (tAN)

Group II: 2 Weeks Sham tAN followed by 2 Weeks Active tAN Experimental Treatment 1 Intervention

Participants will be randomized to receive 2 weeks of at-home, self-administered sham Transcutaneous Auricular Neurostimulation (tAN), followed by 2 weeks of at-home, self-administered active Transcutaneous Auricular Neurostimulation (tAN).

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Published Research Related to This Trial

Transcutaneous auricular vagus nerve stimulation (taVNS) showed promising results in two patients with structural focal epilepsy, leading to seizure freedom in one patient after 4 weeks and significant reduction in seizures for the other after 20 weeks.

Both patients experienced improved quality of life with no significant adverse events reported, suggesting that taVNS could be a safe and effective treatment option for individuals with focal epilepsy and preserved cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulation therapy in patients with cognitively preserved structural focal epilepsy: A case series report. Shiraishi, H., Egawa, K., Murakami, K., et al.[2023]

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 with 66 healthy participants, transcutaneous auricular vagus nerve stimulation (taVNS) did not significantly affect markers of noradrenergic activity, despite expectations that it would enhance this activity.

The results indicated that continuous taVNS stimulation at the tested parameters was ineffective in modulating both phasic and tonic noradrenergic responses, suggesting that this method may not be a viable approach for increasing noradrenergic activity through vagal pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No evidence for a modulating effect of continuous transcutaneous auricular vagus nerve stimulation on markers of noradrenergic activity. D'Agostini, M., Burger, AM., Villca Ponce, G., 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) 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]

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 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]

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]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT06548594

Study Details | NCT06548594 | Out of State - tAN hEDS Specific Aim: Investigate whether 4 weeks of at-home transcutaneous auricular VNS (tAN) improves a battery of nine key physical and psychological symptoms of a ...

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. 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 ...

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

The effects of transcutaneous auricular vagus nerve ... We evaluated SAI bilaterally over the motor cortex before and after exposure to taVNS. Results. No side effects were reported by any of the participants.