Out of State - tAN hEDS

Out-of-State, At-Home, Transcutaneous Auricular Neuromodulation for Hypermobile Ehlers Danlos Syndrome

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.

Study Overview

• Status: Completed
• Conditions: Hypermobile EDS (hEDS)
• Intervention / Treatment: Device: Transcutaneous Auricular Neurostimulation

Detailed Description

The Ehlers-Danlos syndromes (EDS) are a group of heritable, connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility2. Hypermobile EDS (hEDS) is the most common type of EDS and is estimated to affect 1 in 500 individuals worldwide1. Note that there are specific clinical criteria for hEDS and those who do not meet all of them but have a number of similar symptoms are usually classified with hypermobility spectrum disorder (HSD). When investigators use the term hEDS investigators include those with HSD as well. hEDS is characterized by broad tissue/organ involvement across multiple systems and incomplete penetrance. Of particular interest for the proposed work, the vagus nerve has afferent and efferent interactions with nearly all of the affected systems (i.e., cardiovascular, GI, immune system, neurologic function). hEDS is a chronic and debilitating disease that oftentimes begins during childhood and worsens at the time of puberty3. In general, hEDS affects women more severely than men and they are more frequently diagnosed. Treatment options are limited to symptom management and may include physical therapy, bracing and mobility aids, pain management and medication for co-morbid conditions. Surgical intervention is frequent in hEDS patients with an average of 4-5 surgeries required prior to the age of 25 and some are left bed bound and severely handicapped. According to recent reports, 50% of hEDS patients have considered suicide due to not only chronic pain, depression and surgeries, but sadly due to physician-patient interactions being dismissive.

hEDS is viewed as the most neglected disease in modern medicine. The healthcare burden is significant with annual costs estimated at ~$100K/year/patient with a total cost of $3-10M over a lifetime per patient. Physicians are taught limited and misleading information in medical school that Ehlers Danlos Syndromes are benign and rare diseases. These education deficiencies combined with phenotype heterogeneity result in diagnostic challenges. Consequentially, the average time to diagnosis from first symptoms is 14 years. The proposed studies in this application are an important step in transforming how the disease is viewed and understood in the medical community and will provide hope to the many patients with hEDS.

As there is little known about the etiology of the multi-system dysfunction and co-morbidities in hEDS, investigators propose an exploratory study of wide breadth to search for the most promising follow-up investigations. To that end, our main goal is to establish a human trial to investigate the effect of hEDS on multiple body systems and the potentially beneficial effects of an intervention known to have effects on most of those same body systems (vagus nerve stimulation - VNS). Investigators propose to advance mechanistic understanding of hEDS and to test a new therapeutic approach.

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 group of hEDS patients (n=36) using an open-label active only design. Investigators will remotely collect clinical measures at baseline, and weekly timepoints through week 4, as well as a 3 month follow up. Investigators will test patients in the following domains: pain, fatigue, sleep, anxiety, depression, quality of life, GI function, immune function and autonomic function.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina Institute of Psychiatry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ages of 18 and 65;
• Participants who meet the 2017 diagnostic criteria for hEDS or HSD4-5 with persistent symptoms in at least two of the domains to be followed during the intervention (pain, fatigue, sleep, anxiety, depression, quality of life, GI function, autonomic function and immune function)
• Mentally capable of reading, writing, giving consent, and following instructions;

Exclusion Criteria:

• Mentally capable of reading, writing, giving consent, and following instructions;
• Not pregnant;
• No history of seizures;
• no prior history of trauma or damage to ear
• History of documented Autism spectrum disorder (ASD) diagnosis
• Residing in the state of South Carolina

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Four Weeks of Active Transcutaneous Auricular Neurostimulation; Participants will receive 4 weeks of at-home, self-administered active Transcutaneous Auricular Neurostimulation (tAN).	Device: Transcutaneous Auricular Neurostimulation; Transcutaneous Auricular Neurostimulation (tAN) is a wearable, electrical stimulation device that delivers electricity to specific parts of the human ear.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ehlers-Danlos Syndrome Symptom Battery	The investigators have created an Ehlers-Danlos Syndrome Symptom Battery that measures a variety of different primary and secondary symptoms associated with Ehlers-Danlos Syndrome, including: Pain, Fatigue, Sleep, Anxiety, Depression, Quality of Life, and Gastrointestinal issues.	4 weeks

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: MUSC Blue Sky initiative
• Investigators: Principal Investigator: Jeffrey Borckardt, PhD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2024
• Primary Completion (Actual): March 29, 2026
• Study Completion (Actual): March 29, 2026

Study Registration Dates

• First Submitted: August 7, 2024
• First Submitted That Met QC Criteria: August 7, 2024
• First Posted (Actual): August 12, 2024

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Brain
• Additional Relevant MeSH Terms: Ehlers-Danlos syndrome type 3
• Other Study ID Numbers: Pro00138254

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No