Auricular Vagal Nerve Stimulation for Hypermobile Ehlers-Danlos Syndrome

Summary

Hypermobile Ehlers-Danlos Syndrome (hEDS) is a connective tissue disorder characterized by hyperextensible skin, joint hypermobility and additional connective tissue manifestations. For unclear reasons, hEDS is associated with many gastrointestinal (GI) and autonomic nervous system (ANS) complaints such as postural orthostatic tachycardia syndrome (POTS). This study will address the clinical relationship between hEDS/Hypermobile Spectrum Disorders and autonomic regulation and see if there is a benefit of two forms of non-invasive vagal nerve stimulation therapies to reduce GI symptoms in hEDS and POTS. The study will also investigate plausible effects of these nerve stimulation therapies on gastric function and autonomic signaling.

Conditions

• Functional Gastrointestinal Disorders
• Hypermobile Ehlers-Danlos Syndrome
• Postural Orthostatic Tachycardia Syndrome
• Autonomic Nervous System Disease
• Autonomic Nervous System Imbalance

Interventions

DEVICE

Percutaneous vagal nerve stimulation (pVNS) device

Subjects in Treatment Arm B will enter a six-week, prospective open label treatment trial with the FDA-approved and commercially available device IB-Stim. This is an ambulatory, neurostimulation device which consists of a battery powered, externally affixed generator with 4 wire leads attached to electrode/needle arrays affixed to the outer ear. The device delivers low voltage (3.2V) stimulation in alternating frequencies for a total of 5 days (around the clock).

OTHER

Acoustic vagal nerve stimulation (aVNS) treatment

All subjects receiving acoustic therapy via active VNS (aVNS; n=30) or sham VNS (sVNS; n=30) will enter a four-week, randomized, double-blind clinical trial during which they will listen to either computer altered/filtered vocal music (active treatment) that has been designed to stimulate vagal calming vs. regular non-filtered music (sham treatment). The stimuli will mirror the acoustic intervention known as the Safe and Sound Protocol. This protocol has been found to reduce auditory hypersensitivities and calming the autonomic nervous system by increasing vagal regulation of the heart via brainstem ventral vagal complex. The acoustic intervention may be played by an electronic device (i.e. smartphone, tablet, laptop, mp3) and delivered virtually with the help of trained coaches.

Sponsors & Collaborators

• University College, London

  collaborator OTHER

• Indiana University

  collaborator OTHER

• Medical College of Wisconsin

  lead OTHER

Principal Investigators

• Katja Karrento, MD · Medical College of Wisconsin

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

10 Years

Max Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-04-05

Primary Completion

2026-12-31

Completion

2026-12-31

FDA Device

Yes

Countries

• United States

Study Locations