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?
2 other identifiers
observational
120
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for all trials
Started May 2024
Longer than P75 for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 29, 2024
CompletedFirst Submitted
Initial submission to the registry
July 23, 2024
CompletedFirst Posted
Study publicly available on registry
September 27, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 1, 2028
September 26, 2025
September 1, 2025
4.1 years
July 23, 2024
September 24, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
Functional Disability Inventory (FDI)
The total score determines the level of functional disability, in which higher numbers represent a higher level of disability. There are 15-items and a score of 0 indicates that there are no complaints present whereas 30 indicates that the patient is extremely disabled. The Functional Disability Inventory (FDI) is one of the most widely used measures of functional impairment among children and adolescents with chronic pain. It is expected that there will be higher threat sensitivity that correlates with POTS severity (FDI score) across the POTS cohort, and within subjects based on clinical evolution.
Experimental Cohort: Baseline and monthly for 24 months (3, 6, 12, 24 in-person study visits), the other months will be completed from home. The control cohort: months 0-12
Pain Coping Questionnaire short form
The Pain Coping Questionnaire (PCQ) is a 39-item self-report measure for evaluating pain coping in children and adolescents in both clinical and research settings. It consists of 8 subscales that can be categorized into 3 higher-order factors, including approach (composed of information seeking, problem-solving, and seeking social support subscales), problem-focused avoidance (composed of positive self-statements, behavioural distraction, and cognitive distraction subscales), and emotion-focused avoidance (composed of externalizing and internalizing/catastrophizing subscales). Higher scores indicate higher use of a particular coping strategy or style.
Experimental Cohort: Baseline and monthly for 24 months (3, 6, 12, 24 in-person study visits), the other months will be completed from home. The control cohort: months 0-12
Pain Catastrophizing Scale (PCS-C)
The Pain Catastrophizing Scale for Children (PCS-C) is a 13-item self-report scale that measures how children think negatively about pain. The PCS-C asks respondents to rate how often they have pain-related thoughts and feelings on a scale of 0-4, with 0 meaning "not at all true" and 4 meaning "very true". The PCS-C is scored 1) Total score: The sum of all responses, ranging from 0-52, with higher scores indicating more catastrophic thinking 2) Subscale scores: The PCS-C assesses three dimensions of pain catastrophizing: rumination, magnification, and helplessness
Experimental Cohort: Baseline and monthly for 24 months (3, 6, 12, 24 in-person study visits), the other months will be completed from home. The control cohort: months 0-12
Functional MRI (fMRI) scan while completing a complete a looming animacy threat task; participants judge the valence of images via button press as they perceive the image.
Functional MRI is a type of MRI scan that can show which areas of your brain are most active. Tracking and comparing that activity to what you were doing at the time can help "map" your brain activity. It's most often used for planning surgery or similar procedures in the brain. Functional MRI (fMRI) scan in this study will be completed while completing a looming animacy threat task; participants judge the valence of images via button press as they perceive the image.
Experimental cohort: Baseline, 3, 6, 12, 24 month in person visits. Control Cohort: Baseline, 3, 6, and 12 month in person visits.
Bedside Tilt test
A tilt table test, also known as a tilt test, is a procedure that helps determine the cause of fainting or near fainting spells. It involves lying on a table that's tilted to different positions while a medical professional monitors your heart rate, blood pressure, and oxygen levels.
Experimental cohort: Baseline, 3, 6, 12, 24 month in person visits. Control Cohort: Baseline, 3, 6, and 12 month in person visits.
Study Arms (3)
60 POTS Postural Tachycardia Syndrome (POTS)
POTS patients will be current patients of the study practitioners within the autonomic, cardiology PM\&R clinics and autonomic laboratory. This cohort may receive a codified treatment plan within the following 7 treatment categories which are also standard of care procedures based on clinical recommendations: (1) salt, fluid and diet management; (2) exercise program with or without PT; (3) cognitive behavioral therapy or other counseling; (4) vagal stimulation forms like yoga, breathing exercises, relaxation, microauricular stimulation; (5) pharmacotherapy for pressure maintenance; (6) medications for pain and headache; (7) medications for the gastrointestinal issues.
40 Post-Infection cohort
Post-Infection participants will be identified through Best Practice Alerts through EPIC, and referrals from hospitalist and gastroenterology inpatient services. Post-Infection cohorts will be approached up to 6 weeks after they are released from the hospital, to ensure they are healthy enough to participate.
20 healthy controls
Healthy control participants will be recruited from local communities using flyers, social media and using EPIC Best Practice Alerts.
Interventions
* 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)
Participants will provide a list of all medications taken at each visit time, lifetime history of infections, traumas, and other significant 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
Participants will have an activity monitor loaned for the duration of the study to track their physical activity.
POTS patients will have a periodic 24-hour urine sodium check to determine compliance to intake of salt.
• 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.
A bedside tilt test will be performed where blood pressure will be recorded supine and upright positions to confirm/exclude POTS.
• 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.
• 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
Eligibility Criteria
The study aims to recruit only females aged 12-21. Females will be targeted specifically since POTS is more common in females than males and avoids creation of a subgroup too small to analyze.
You may qualify if:
- symptomatic ≥ 40 bpm rise in heart rate in the first 10 min of a tilt table study without a drop in blood pressure
- Clinical symptoms of orthostatic intolerance
You may not qualify if:
- Pregnant or breastfeeding
- Cognitive defects that preclude answering questionnaires or following assessment directions
- Other chronic diseases
- Unstable medical conditions
- Use of narcotics
- Limited English proficiency
- Investigator discretion that participant would not be suitable to participate
- A phone older than 5 years old or unable to support EMA software
- POST INFECTION
- acute upper respiratory or gastrointestinal infection that required admission to the acute care units but not requiring an ICU stay
- Pregnant or breastfeeding
- Chronic prescriptions, history of POTS or orthostatic symptoms, recent inpatient psychiatric admissions, substance use disorder, trauma such as a motor vehicle accident, surgery, or other significant physical or emotional trauma in the last 5 years
- Cognitive defects that preclude answering questionnaires or following assessment directions
- Other unstable chronic diseases
- Unstable medical conditions
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Virginia Commonwealth University
Richmond, Virginia, 23298, United States
Biospecimen
-Stool samples will be sent for analysis, they will then be de-identified and stored in a -80 C freezer at VCU for future research purposes
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Gisela Chelimsky
Virginia Commonwealth University
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 23, 2024
First Posted
September 27, 2024
Study Start
May 29, 2024
Primary Completion (Estimated)
July 1, 2028
Study Completion (Estimated)
July 1, 2028
Last Updated
September 26, 2025
Record last verified: 2025-09