Does a Periaqueductal Gray-vagus Nerve Interface Malfunction Explain the Nat hx With Its Numerous Co-morbidities?
NCT ID: NCT06616363
Last Updated: 2025-09-26
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
120 participants
OBSERVATIONAL
2024-05-29
2028-07-31
Brief Summary
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Detailed Description
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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
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Study Design
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COHORT
PROSPECTIVE
Study Groups
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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.
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)
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.
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
Will wear an activity monitor
Participants will have an activity monitor loaned for the duration of the study to track their physical activity.
Periodic 24-hour urine sodium check
POTS patients will have a periodic 24-hour urine sodium check to determine compliance to intake of salt.
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.
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.
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.
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
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.
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)
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.
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
Will wear an activity monitor
Participants will have an activity monitor loaned for the duration of the study to track their physical activity.
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.
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.
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.
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
20 healthy controls
Healthy control participants will be recruited from local communities using flyers, social media and using EPIC Best Practice Alerts.
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)
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.
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
Will wear an activity monitor
Participants will have an activity monitor loaned for the duration of the study to track their physical activity.
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.
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.
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.
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
Interventions
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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)
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.
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
Will wear an activity monitor
Participants will have an activity monitor loaned for the duration of the study to track their physical activity.
Periodic 24-hour urine sodium check
POTS patients will have a periodic 24-hour urine sodium check to determine compliance to intake of salt.
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.
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.
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.
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
Eligibility Criteria
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Inclusion Criteria
* Clinical symptoms of orthostatic intolerance
* acute upper respiratory or gastrointestinal infection that required admission to the acute care units but not requiring an ICU stay
* Apparently healthy with no known chronic illnesses
Exclusion Criteria
* 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
* 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
* 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
12 Years
21 Years
FEMALE
Yes
Sponsors
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National Heart, Lung, and Blood Institute (NHLBI)
NIH
Virginia Commonwealth University
OTHER
Responsible Party
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Principal Investigators
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Gisela Chelimsky
Role: PRINCIPAL_INVESTIGATOR
Virginia Commonwealth University
Locations
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Virginia Commonwealth University
Richmond, Virginia, United States
Countries
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Central Contacts
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Facility Contacts
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Other Identifiers
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HM20029682
Identifier Type: -
Identifier Source: org_study_id
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