NCT06616363

Does a Periaqueductal Gray-vagus Nerve Interface Malfunction Explain the Nat hx With Its Numerous Co-morbidities?

(PAG POTS - NIH) Pediatric Postural Orthostatic Tachycardia Syndrome (POTS) : Does a Periaqueductal Gray-vagus Nerve Interface Malfunction Explain the Natural History With Its Numerous Co-morbidities?

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 120 (estimated)
• Sponsor: Virginia Commonwealth University · Academic / Other
• Sex: Female
• Age: 12 Years – 21 Years
• Healthy volunteers: Accepted

Summary

Postural tachycardia syndrome (POTS) is a common and disabling disorder among adolescents. No epidemiologic data exist to support the often cited 0.5 to 2% prevalence. Case series suggest 3 to 5 times greater incidence in girls than boys. POTS is defined in children as daily chronic symptoms of orthostatic intolerance and a 40 bpm rise in heart rate in the first 10 minutes of a tilt study in the absence of orthostatic hypotension. POTS often develops after an acute event like an illness, infection, immunization, head trauma, psychological trauma or surgery. Natural history data are absent for POTS, though some outcome studies exist. Orthostatic symptoms improve in the majority and heart rate changes improve in 38% at 1 year. A 2-year follow up showed small improvement in comorbid symptoms of POTS in a 12 subject cohort followed yearly. In a pediatric 5-year outcome follow up questionnaire study, 86% of adolescents with POTS reported resolved, improved, or intermittent, symptoms, with primarily physical rather than mental health complaints.

Detailed description

The current definition of POTS highlights the peripheral mechanistic emphasis of 30 years of studies exploring cardio- and cerebro-vascular, immunologic, mast cell activation, connective tissue and other physiologic mechanisms. The classification of POTS itself also assumes a peripheral etiology, typically including neuropathic, hyperadrenergic, hypovolemic and sometimes immune POTS. However, a central nervous system (CNS) etiology might better account for what is knowns about POTS currently: (1) POTS often follows an infection, physical or psychological trauma. (2) POTS occurs most often in post-menarche adolescent girls volume redistribution differs across subjects (4) exercise, cognitive behavioral therapy provide best long-term outcomes (5) co-morbid disorders, typically overlapping pain conditions such as migraine headache, fibromyalgia, and most functional gastrointestinal disorders (FGID), often dominate the clinical picture. COPCs are typically considered to reflect a CNS etiology. Because it coordinates the autonomic, motor and pain responses to an acute threat, the midbrain periaqueductal gray region (PAG) is an attractive candidate whose dysfunction could potentially explain all major features of POTS, including the frequent antecedent emotional or physical threat, the POTS core autonomic changes, and the co-morbid pain disorders. The PAG interprets threats as escapable or inescapable, specifically activating a different column for each response type.

Conditions

• POTS - Postural Orthostatic Tachycardia Syndrome

Interventions

Type	Name	Description
BEHAVIORAL	Questionnaires to be competed	* The Pain Coping Questionnaire short form * Functional Disability Inventory (FDI), the primary clinical outcome measure. * COMPASS-31 and orthostatic hypotension modified for POTS. * The Pain Response Inventory (PRI)PROMIS Depression * GAD-7 for anxiety * Varni/Thompson Pediatric Pain Questionnaire * Child and Parent Reports of Post-Traumatic Symptoms (CROPS/PROPS) * Pain Catastrophizing Scale (PCS-C) * Detailed account of natural history and evolution of POTS and COPCs through MEDYSA (facilitates the assessment of specific syndromic diagnoses based on published criteria, rather than organ-based classification of symptoms)
BEHAVIORAL	Provide list of medication and lifetime events	Participants will provide a list of all medications taken at each visit time, lifetime history of infections, traumas, and other significant life events.
BEHAVIORAL	Use phone App to record new life events	Subjects will also record new life events, minor traumas, entrance into a flare and menses in Ilumivu's EMA (Ecological Momentary Assessment) phone App
DEVICE	Will wear an activity monitor	Participants will have an activity monitor loaned for the duration of the study to track their physical activity.
OTHER	Periodic 24-hour urine sodium check	POTS patients will have a periodic 24-hour urine sodium check to determine compliance to intake of salt.
DIAGNOSTIC_TEST	A fMRI scan	• Participants will complete a fMRI scan without contrast and complete a looming animacy threat task; participants judge the valence of images via button press as they perceive the image.
DIAGNOSTIC_TEST	A bedside tilt test will be performed	A bedside tilt test will be performed where blood pressure will be recorded supine and upright positions to confirm/exclude POTS.
OTHER	IV placed to collect blood samples	• An IV will be place for collection of 4 blood samples, about 12 mL of blood. For each position (lying and standing) the study team will draw 2 tubes each times with 3 mL of blood, for a total of 4 lab tubes (12 mL). Physical exams to assess the 18-tender points described by the American College of Rheumatology for the diagnosis of fibromyalgia and hypermobility/Ehlers-Danlos Syndrome (EDS) exam will be performed in all subjects.
OTHER	Stool Sample	• Participants will provide a stool biospecimen sample at each in-person visit. Stool will be collected in a hat and sample will be swabbed with the swab placed directly into PrimeStore collection tube and the remainder of the sample discarded

Timeline

• Start date: 2024-05-29
• Primary completion: 2028-07-01
• Completion: 2028-07-01
• First posted: 2024-09-27
• Last updated: 2025-09-26

Locations

1 site across 1 country: United States