Autonomic Nervous System Disease, Autonomic Nervous System Imbalance, Functional Gastrointestinal Disorders, Hypermobile Ehlers-Danlos Syndrome, Postural Orthostatic Tachycardia Syndrome
Conditions
Brief 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.
Detailed description
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?
Interventions
DEVICEPercutaneous 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).
OTHERAcoustic 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
Medical College of Wisconsin
University College, London
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Treatment Arm A is masked (double-blinded). Treatment Arm B is not masked.
Intervention model description
Participants enrolled in either Treatment Arm A (randomized to active vs sham therapy) or Treatment Arm B at the same time throughout the enrollment process.
Eligibility
Sex/Gender
ALL
Age
10 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Children aged 10-18 years old * Children with functional upper GI complaints and clinical suspicion for hEDS or HSD as well as a Beighton score of at least 4/9 * Children with functional upper GI complaints and clinical suspicion for ANS dysfunction * De-identified data from our prior studies (IRB #689519 and IRB #1064187) of patients with functional GI disorders who do NOT meet criteria for hEDS will be used as a comparison group * Children who are English-speaking and lack other explanation for symptoms * Children willing to participate and consent to this study (for children, have a parent willing to participate)
Exclusion criteria
A)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in gastrointestinal symptoms as assessed by the instrument Patient Assessment of upper Gastrointestinal Symptom Severity Index (PAGI-SYM) | Change from baseline total PAGI-SYM score at end of therapy (6 weeks) | Instrument assessing upper gastrointestinal symptoms including symptoms of gastroparesis; score range 0-100 with higher scores indicating worse symptoms |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in gastric motor function as assessed by gastric MRI | Change from baseline at end of therapy (6 weeks) | 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. |
| Change in Body Perception Questionnaire (BPQ) total score | Change from baseline at end of therapy (6 weeks) | Instrument assessing symptoms of autonomic reactivity; raw score range 0-130 with higher score indicating greater autonomic reactivity |
| Change in vagal efficiency measurements | Change from baseline at end of therapy (6 weeks) | Metrics of vagal tone extracted from ECG R-R interval data measurements during postural challenges |
Countries
United States
Contacts
CONTACTKatja Karrento, MD
PRINCIPAL_INVESTIGATORKatja Karrento, MD
Medical College of Wisconsin
Outcome results
None listed