NCT06616363 · Virginia Commonwealth University
Does a Periaqueductal Gray-vagus Nerve Interface Malfunction Explain the Nat hx With Its Numerous Co-morbidities?
What this study is about
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.
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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.
Interventions
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
Primary outcome measures
Functional Disability Inventory (FDI)
Time frame: 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
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.
Pain Coping Questionnaire short form
Time frame: 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
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.
Pain Catastrophizing Scale (PCS-C)
Time frame: 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
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
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.
Time frame: Experimental cohort: Baseline, 3, 6, 12, 24 month in person visits. Control Cohort: Baseline, 3, 6, and 12 month in person visits.
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.
Bedside Tilt test
Time frame: Experimental cohort: Baseline, 3, 6, 12, 24 month in person visits. Control Cohort: Baseline, 3, 6, and 12 month in person visits.
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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
Exclusion criteria
- 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 Inclusion Criteria:
- acute upper respiratory or gastrointestinal infection that required admission to the acute care units but not requiring an ICU stay Exclusion Criteria:
- 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
- Use of narcotics
- Severe depression or anxiety (untreated / unstable)
- 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 HEALTHY CONTROLS Inclusion Criteria:
- Apparently healthy with no known chronic illnesses Exclusion Criteria:
- Pregnant or breastfeeding
- History of POTS or orthostatic symptoms, migraines, fibromyalgia, chronic fatigue, PTSD. Functional gastrointestinal disorders, fainting, dysmenorrhea, or other chronic pain syndrome, 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 chronic unstable diseases
- Unstable medical conditions
- Use of narcotics
- Severe depression or anxiety (untreated / unstable)
- 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
Where
- Richmond, Virginia
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Sep 26, 2025 · Source of record for eligibility and locations