Functional Gastrointestinal Disorders Clinical Trial
Official title:
Hypermobile Ehlers-Danlos Syndrome: Efficacy of Non-invasive Vagal Nerve Stimulation and Effects on Brain-Gut Physiology
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.
Status | Recruiting |
Enrollment | 90 |
Est. completion date | December 31, 2024 |
Est. primary completion date | December 31, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 10 Years to 18 Years |
Eligibility | 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) Exclusion Criteria applying to all participants: - 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. B) Exclusion Criteria for subjects undergoing pVNS therapy: - Severe dermatological condition or active infection of external or middle ear - Implanted electrical device C) Exclusion Criteria for subjects undergoing aVNS therapy: - Hearing impaired - Sight impaired without correction - Seizure disorder D) Exclusion Criteria for subjects undergoing gastric motor function sub-study: - 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 E) Exclusion Criteria for subjects undergoing HepGI Biobank specimen collection sub-study: - 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. |
Country | Name | City | State |
---|---|---|---|
United States | Medical College of Wisconsin | Milwaukee | Wisconsin |
Lead Sponsor | Collaborator |
---|---|
Medical College of Wisconsin | Indiana University, University College, London |
United States,
Castori M, Tinkle B, Levy H, Grahame R, Malfait F, Hakim A. A framework for the classification of joint hypermobility and related conditions. Am J Med Genet C Semin Med Genet. 2017 Mar;175(1):148-157. doi: 10.1002/ajmg.c.31539. Epub 2017 Feb 1. — View Citation
Gazit Y, Nahir AM, Grahame R, Jacob G. Dysautonomia in the joint hypermobility syndrome. Am J Med. 2003 Jul;115(1):33-40. doi: 10.1016/s0002-9343(03)00235-3. — View Citation
Kovacic K, Chelimsky TC, Sood MR, Simpson P, Nugent M, Chelimsky G. Joint hypermobility: a common association with complex functional gastrointestinal disorders. J Pediatr. 2014 Nov;165(5):973-8. doi: 10.1016/j.jpeds.2014.07.021. Epub 2014 Aug 20. — View Citation
Kovacic K, Hainsworth K, Sood M, Chelimsky G, Unteutsch R, Nugent M, Simpson P, Miranda A. Neurostimulation for abdominal pain-related functional gastrointestinal disorders in adolescents: a randomised, double-blind, sham-controlled trial. Lancet Gastroenterol Hepatol. 2017 Oct;2(10):727-737. doi: 10.1016/S2468-1253(17)30253-4. Epub 2017 Aug 18. — View Citation
Porges SW, Davila MI, Lewis GF, Kolacz J, Okonmah-Obazee S, Hane AA, Kwon KY, Ludwig RJ, Myers MM, Welch MG. Autonomic regulation of preterm infants is enhanced by Family Nurture Intervention. Dev Psychobiol. 2019 Sep;61(6):942-952. doi: 10.1002/dev.21841. Epub 2019 Mar 13. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Change from baseline total PAGI-SYM score at end of therapy (6 weeks) | |
Secondary | 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. | Change from baseline at end of therapy (6 weeks) | |
Secondary | 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 | Change from baseline at end of therapy (6 weeks) | |
Secondary | Change in vagal efficiency measurements | Metrics of vagal tone extracted from ECG R-R interval data measurements during postural challenges | Change from baseline at end of therapy (6 weeks) |
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