Postural Tachycardia Syndrome Clinical Trial
Official title:
The Pathophysiological Role of Adrenergic Antibodies in Postural Tachycardia Syndrome (Aims #1&2)
Objective: In this pilot study, we will test the hypothesis that patients with POTS (age 18-60 years) will have a higher percentage of functional antibodies to adrenergic receptors compared with control subjects without POTS.
Background & Rationale: Postural Tachycardia Syndrome (POTS) is a chronic state of orthostatic tachycardia (> 30 bpm increment from lying to standing) and typical symptoms that are worse on standing, and are relieved by lying down. Typical orthostatic symptoms include palpitation, lightheadedness, chest pains, dyspnea, tremulousness, blurred vision and mental clouding. POTS often occurs in younger individuals with a female predominance (4-5 fold). Using the RAND36 quality of life (QOL) tool, we showed that POTS patients had lower quality of life (QOL) scores than healthy subjects for both physical (26±9 vs. 54±6; P<0.0001) and mental health domains (43±11 vs. 52±10; P<0.0001). These QOL scores are similar to scores for chronic obstructive pulmonary disease and congestive heart failure. In collaboration with the Kem/Yu lab (Oklahoma University), the investigators sought to determine whether POTS patients had functionally significant adrenergic receptor (AR) Abs. Samples from 14 POTS patients (included 7 blinded, well-characterized samples from Vanderbilt) and 10 healthy control subjects. Using the rat cremaster artery assay, the sera/immunoglobulin (IgG) of the POTS patients demonstrated significantly greater arteriolar contractile activity (69±3% of baseline vessel diameter) compared to the control subjects (91±1% of baseline; P<0.001). This contractility was suppressed with prazosin, an α1-AR blocker. With the addition of POTS sera, the phenylephrine dose-response curve was shifted to the right. In other words, a higher dose of phenylephrine was required to achieve the same degree of vasoconstriction, suggests that the α1-AR Ab is actually a partial-agonist/antagonist. Using a cell-based cyclic AMP (cAMP) reporter assay, all POTS sera had dose-dependent β1-AR activation (max: +30±3% from buffer baseline) compared to control sera (-1±2% from buffer baseline; P<0.001), and 7/14 POTS patients (but no control subjects) had elevated β2-AR activation. The excessive β1-AR activation could be blocked with propranolol. With the addition of POTS sera, the isoproterenol dose-response curve was shifted to the left (a lower isoproterenol dose was required to achieve the same receptor activation in the presence of the POTS sera). These data suggest that the β1-AR Ab is actually a straight agonist. Big Picture: While exciting, these data are obtained from only 14 POTS patients. In this protocol (Aim#1; REB15-2434), the investigators will study a larger cohort of POTS patients and control subjects in order to have a better sense of the true prevalence of these antibodies, to determine their association with other autoimmune illnesses, and to see if they relate to the patient-reported onset of illness. In addition to this, the investigators seek to see whether this is physiologically significant in intact humans in vivo (Aim#2). The investigators propose to perform dose response studies for phenylephrine and isoproterenol in POTS patients and control subjects with blood pressure (BP) and heart rate (HR) as the output metric and will then determine if these are different between POTS patients and control subjects and, more importantly, based on the auto-antibody in vitro activity. Specifically, the investigators will give a series of injections of small doses of phenylephrine while monitoring their HR and continuous BP. After each injection, the investigators will note the peak BP increase and will monitor the patient until the BP returns to baseline. The investigators will give incrementally larger doses until the endpoint is achieved. The endpoint is the lowest test dose of phenylephrine that will increase the systolic BP by >25 mmHg (PHE-PD25). the investigators will then repeat the same process with small doses of isoproterenol with the same monitoring. After each injection, the investigators will note the peak HR increase and will monitor the patient until the HR returns to baseline. The investigators will give incrementally larger doses until the endpoint is achieved. The endpoint is the lowest test dose of isoproterenol that will increase the HR by >25 bpm (ISO-PD25). ;
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT03124355 -
Vagal Stimulation in POTS
|
Phase 1 | |
Recruiting |
NCT04310644 -
Autonomic Small Fiber Neuropathy and Ehlers Danlos Syndromes - Prospective Study and Registry
|
||
Completed |
NCT03253120 -
Alterations of Attention in POTS Depending on Body Position and Hydration
|
N/A | |
Completed |
NCT03919773 -
IVIG (Gamunex-C) Treatment Study for POTS Subjects
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT01988883 -
Modafinil and Cognitive Function in POTS
|
Early Phase 1 | |
Active, not recruiting |
NCT01000350 -
Intravenous (IV) Saline and Exercise in Postural Tachycardia Syndrome (POTS)
|
N/A | |
Recruiting |
NCT00409435 -
A Study of Pyridostigmine in Postural Tachycardia Syndrome
|
Phase 2 | |
Completed |
NCT00770484 -
Effect of Exercise in OI
|
N/A | |
Completed |
NCT00581022 -
Objective Sleep Disturbances in Orthostatic Intolerance
|
||
Terminated |
NCT00748228 -
Dopamine in Orthostatic Tolerance
|
N/A | |
Active, not recruiting |
NCT05630040 -
VNS for Long-COVID-19
|
N/A | |
Recruiting |
NCT04632134 -
Long-term Effects of Transcutaneous Vagal Nerve Stimulation on Postural Orthostatic Tachycardia Syndrome (POTS)
|
N/A | |
Completed |
NCT00685919 -
Peripheral Dopamine in Postural Tachycardia Syndrome
|
Phase 2/Phase 3 | |
Completed |
NCT00061009 -
Hypnosis in Autonomic Function
|
N/A | |
Recruiting |
NCT05618054 -
Periaqueductal Gray-vagus Nerve Interface Malfunction Explain the Natural History With Its Numerous Co-morbidities?
|
N/A | |
Completed |
NCT01366963 -
Cognitive Dysfunction in Postural Tachycardia Syndrome
|
N/A | |
Recruiting |
NCT05107635 -
Inappropriate Sinus Tachycardia Registry
|
||
Terminated |
NCT02154009 -
Clinical Autonomic Disorders: A Training Protocol
|
||
Completed |
NCT03602482 -
Standing Cognition and Co-morbidities of POTS Evaluation
|
N/A | |
Completed |
NCT02167412 -
EEG Characteristics in Youth POTS and/or Syncope
|