Clinical trial NCT02196376: Assessment of Antibodies and Inflammatory Markers in Postural Tachycardia Syndrome
Official title: Assessment of Antibodies and Inflammatory Markers in Postural Tachycardia Syndrome
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Postural Orthostatic Tachycardia Syndrome
Keywords: Postural orthostatic syndrome
orthostatic intolerance
autonomic dysfunction
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2014-07-22
Enrollment: 212
Sex: ALL
Minimum age (years): 13
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Chronic orthostatic intolerance, sometimes known as the postural tachycardia syndrome (POTS), is the most common disorder among patients seen at several centers specializing in diseases of the autonomic nervous system.

excessive increase in heart rate \[\>30 min-1\] on standing associated with orthostatic symptoms \[including palpitation, chest pain syndrome, dyspnea on standing, mental clouding and difficulties with concentration\], in the absence of orthostatic hypotension. Orthostatic tachycardia can produce substantial disability among otherwise healthy people. Patients typically feel tired and run down. Many also report a myriad of symptoms that are hard to categorize, often involving fatigue. We and others have reported that patients had a diminished quality of life.

Brief summary: In this pilot study, the investigators will test the hypothesis that patients with postural tachycardia syndrome will have an elevated percentage of functional antibodies to adrenergic receptors compared with control subjects without POTS. The investigators further hypothesize that the percentage of POTS patients with antibodies will be higher in those patients with a viral infection at the onset of their illness than in those patients with other or undefined illness onsets.

Detailed description: Postural orthostatic tachycardia syndrome is poorly understood. Many of these patients have elevated levels of plasma norepinephrine, particularly when upright One subgroup of patients has a primary hyperadrenergic state. The majority of patients have a marked deficit in plasma blood volume compared to healthy control subjects. The investigators have previously reported that some patients suffer paradoxically from a partial dysautonomia affecting the lower limbs. Most patients seem to suffer from either a primary or secondary increase in central sympathetic nervous system drive. Recent data have shown that patients with postural orthostatic tachycardia syndrome have a lower cardiac stroke volume than their healthy counterparts and this low stroke volume may drive their orthostatic tachycardia.

The investigators plan to do the following:

The physical examination will include (at minimum):

* Height
* Weight
* Orthostatic vital signs (heart rate and blood pressure) Supine and Standing for up to 10 minutes
* Beighton Criteria for Joint Hypermobility Syndrome (Ehlers-Danlos III)
* Dependent acrocyanosis (during stand test)

Continuous Heart Rate and Blood Pressure Recording A subset of subjects will be given the opportunity to also have continuous recordings of heart rate and blood pressure for 5-10 minutes while lying down quietly. They will be instrumented with EKG patches on their body and a finger blood pressure cuff, and these data will be digitally sampled and acquired on a dedicated laptop computer for later offline analysis.

There will be an optional rider on the consent form to allow the patient to consent to this portion of the study.

Blood work

Blood will be drawn for future assay and analysis of the following tests:

* Antibodies regulating cardiovascular function

  o The clinical significance of these antibodies is unknown. The investigators will share the results of the antibody panel with the subject, but with the caveat that no clinical interpretation or comment on significance can be made.
* Inflammatory markers

The total amount of blood drawn for this project will be less than 15 ml.

Questionnaires

* RAND-36
* Health Thermometer
* Chandler Fatigue Scale
* Daily diary of Fatigue Symptoms - Fibromyalgia
* Pain Detect Questionnaire
* Orthostatic Grading Scale
* COMPASS-31
* Structured History (including some of the elements from section 6.1)

These questionnaires will be completed directly online (web-based interface) using a personalized link that will be provided to the subjects after they give their informed consent. These will be created in a REDCap-Survey environment, with the data collected and stored on a password-protected, HIPAA-compliant, secure computer server.

Eligibility criteria: Inclusion Criteria:

* Postural Tachycardia Syndrome
* Previously diagnosed with POTS
* Control Subjects
* Not diagnosed with POTS
* Age between 13-80 years
* Male and female subjects are eligible.
* Able and willing to provide informed consent

Exclusion Criteria:

* Inability to give, or withdrawal of, informed consent
* Other factors which in the investigator's opinion would prevent the subject from completing the protocol.

Primary outcomes:
measure: Ab titer in POTS patients compared to control subjects
timeFrame: One time only, at first visit
Secondary outcomes:
measure: comparison of the number of POTS patients with viral based Ab versus non-viral based Ab
timeFrame: One time only - at first study visit
measure: comparison of the number of POTS patients with and without Ehlers Danlos syndrome III
timeFrame: One time only - at first study visit
measure: comparison of the number of POTS patients with a history of autoimmune disorders versus no history of auto-immune disorders
timeFrame: One time only - at first study visit
measure: comparison of the number of POTS patients with fatigue versus no history of fatigue based on severity of impact on normal daily activities.
timeFrame: One time only - at first study visit
measure: comparison of pain in POTS patients versus non-POTS patients
timeFrame: One time only - at first study visit
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Satish Raj, MD, MSCI
role: PRINCIPAL_INVESTIGATOR
References: