An interventional study of Percutaneous vagal nerve stimulation (pVNS) device and Acoustic vagal nerve stimulation (aVNS) treatment in Functional Gastrointestinal Disorders, Hypermobile Ehlers-Danlos Syndrome and Postural Orthostatic Tachycardia Syndrome, sponsored by Medical College of Wisconsin. Recruiting at 1 site in United States. Open to participants aged 10 Years to 18 Years. Per ClinicalTrials.gov, last updated 2026-02-13.
Sponsored by Medical College of Wisconsin · Not applicable, Interventional, and Treatment
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.
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 and Hypermobile Spectrum Disorders are associated with many gastrointestinal (GI) and autonomic nervous system (ANS) complaints such as postural orthostatic tachycardia syndrome (POTS). Symptoms are often disabling and associated with poor quality of life and high health care costs. The proposed research will address the following understudied areas: 1) the clinical relationship between hEDS and autonomic regulation, 2) the potential benefit of two forms of non-invasive vagal nerve stimulation (VNS) therapies in reducing functional GI symptoms in hEDS and POTS, and 3) plausible effects of these VNS therapies on gastric motor function and neurohormonal signaling.
Clinical reports document a high co-morbidity between autonomic disorders and hEDS. This prospective study will focus on three major clinical questions: 1) Are there reliable neurophysiological markers associated with hEDS that can provide insights into the 'neural mechanisms' resulting in multisystem co-morbidities? 2) Will innovative intervention techniques designed to enhance autonomic regulation via two non-invasive vagal nerve stimulation techniques (e.g., auricular and acoustic VNS) provide substantial symptom reduction and improve the hEDS patients' quality of life? 3) Can a novel gastric MRI technique capture gastric motor function abnormalities in adolescents with hEDS?
548 studies on the registry are indexed under Gastrointestinal Diseases; 101 are open to participants now.
This study's planned enrollment of 90 is above the median of 80 across 388 interventional studies indexed under Gastrointestinal Diseases.
Browse Gastrointestinal Diseases studies →Medical College of Wisconsin is the lead sponsor of 548 studies on the registry; 122 are open to participants now.
Of its 75 completed or terminated interventional studies of FDA-regulated products, 57 (76%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
A) Exclusion Criteria applying to all participants:
B) Exclusion Criteria for subjects undergoing pVNS therapy:
C) Exclusion Criteria for subjects undergoing aVNS therapy:
D) Exclusion Criteria for subjects undergoing gastric motor function sub-study:
E) Exclusion Criteria for subjects undergoing HepGI Biobank specimen collection sub-study:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
(n=60) patients who meet criteria for hEDS or Hypermobile Spectrum Disorder (HSD) will receive aVNS (acoustic vagal nerve stimulation) therapy via filtered vocal music sound therapy using the Safe and Sound protocol (randomized 1:1 to active vs sham music; double blind study design)
Other: Acoustic vagal nerve stimulation (aVNS) treatment
(n=30) patients with concerns for ANS dysfunction (with or without hEDS) will receive auricular percutaneous vagal nerve stimulation (pVNS) therapy. Additional sub-study option: 15-20 subjects will undergo gastric MRI and (those who consent to it) will also participate in a biobank blood sample collection study.
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).
Also known as: percutaneous electrical nerve field stimulation
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.
Also known as: Safe and Sound Protocol
Change in gastrointestinal symptoms as assessed by the instrument Patient Assessment of upper Gastrointestinal Symptom Severity Index (PAGI-SYM)
Instrument assessing upper gastrointestinal symptoms including symptoms of gastroparesis; score range 0-100 with higher scores indicating worse symptoms
Time frame: Change from baseline total PAGI-SYM score at end of therapy (6 weeks)
Change in gastric motor function as assessed by gastric MRI
Dynamic gastric MRI measure of gastric accomodation as measured by gastric volume change in response to test meal. A greater gastric volume change indicates improved gastric accomodation.
Time frame: Change from baseline at end of therapy (6 weeks)
Change in Body Perception Questionnaire (BPQ) total score
Instrument assessing symptoms of autonomic reactivity; raw score range 0-130 with higher score indicating greater autonomic reactivity
Time frame: Change from baseline at end of therapy (6 weeks)
Change in vagal efficiency measurements
Metrics of vagal tone extracted from ECG R-R interval data measurements during postural challenges
Time frame: Change from baseline at end of therapy (6 weeks)
Plan to share: No
Started Apr 2021 (actual). Primary completion is estimated for Dec 2026, 68 months after the start.
Of 127 non-industry interventional studies with no phase under Gastrointestinal Diseases, half reached primary completion within 26 months of starting (the median), counting those still running; a quarter within 11 and three quarters within 46. This study's planned 68 months is above that.
Counting every sponsor, half of 149 studies reached it within 24 months; a quarter within 10 and three quarters within 45.
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