RecruitingNot ApplicableNCT05212129

Auricular Vagal Nerve Stimulation for Hypermobile Ehlers-Danlos Syndrome

Hypermobile Ehlers-Danlos Syndrome: Efficacy of Non-invasive Vagal Nerve Stimulation and Effects on Brain-Gut Physiology

Sponsor

Medical College of Wisconsin

Enrollment

90 participants

Start Date

Apr 5, 2021

Study Type

INTERVENTIONAL

Conditions

Functional Gastrointestinal Disorders 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.

Eligibility

Min Age: 10 YearsMax Age: 18 Years

Inclusion Criteria6

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 Criteria21

Medically complex children or those who take a medication or suffer from a disease that can explain symptoms will be excluded from participation in the study.
Adult subjects, children or their parents who have significant developmental delay (will be excluded due to difficulties in accurately completing the questionnaires and assessing symptoms)
Patients with findings of organic disease such as peptic ulcer disease, H.pylori gastritis, celiac disease, inflammatory bowel disease, allergic disorders, metabolic disorder or any other chronic condition or medication that may cause chronic GI symptoms will be excluded from the study.
Patients who are treated with a new drug affecting the central nervous system in the two weeks prior to enrollment will also be excluded.
Pregnancy (evaluating MD screens patients as they normally would during a clinic visit (by questioning) and would only perform urine pregnancy test if clinically indicated (absence of menstrual period or other symptoms concerning for pregnancy)
Chronic alcohol/illicit drug use and/or smoking.
Severe dermatological condition or active infection of external or middle ear
Implanted electrical device
Hearing impaired
Sight impaired without correction
Seizure disorder
Patients with pacemakers, metal clips used in previous surgery or other device which are not compatible with MRI scanning
Claustrophobia or inability to lie still in the scanner
Orthodontic braces or permanent retainers
Patients who are unable to tolerate noise produced by the MRI
Egg allergy or anticipated inability to complete a standardized egg meal
Bleeding disorder for the specific biopsies
Recent antibiotic usage for fecal sample
Significant anemia or clinical status which will not allow safe blood draw required for blood collection
Refusal of blood collection or to provide DNA sample
Inability or unwillingness on the individual (or parent/legal guardian) to provide clinical or family history.

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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.