Clinical Trial: POTS Adrenergic Ab (CIHR Aims #1&2)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: The Pathophysiological Role of Adrenergic Antibodies in Postural Tachycardia Syndrome (Aims #1&2)

Brief Summary: 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.

Detailed Summary:

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 ass
Sponsor: University of Calgary

Current Primary Outcome: The proportion of alpha-1 Ab titer positive subjects [ Time Frame: 1 Year (to measure Adrenergic antibody assay) ]

The primary comparison will be the proportion of Ab titers between POTS patients compared to control subjects.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Antibody Positivity by Joint Hypermobility Status [ Time Frame: 1 Year (to measure Adrenergic antibody assay) ]
    These comparisons include proportions of POTS patients with +va adrenergic Ab with a co-diagnosis of joint hypermobility syndrome (EDS III) vs without joint hypermobility syndrome (EDS III).
  • Antibody Positivity by Clinical Autoimmune Syndromes [ Time Frame: 1 Year (to measure Adrenergic antibody assay) ]
    These comparisons include proportions of POTS patients with +ve adrenergic Ab with a co-diagnosis of a clinical autoimmune disorder vs without a clinical autoimmune disorder.
  • Antibody Positivity by Viral Onset of POTS [ Time Frame: 1 Year (to measure Adrenergic Antibody assay) ]
    These comparisons include proportions of POTS patients with +ve adrenergic Ab with a viral onset to their POTS vs without a viral onset to their POTS.
  • Isoproterenol HR Increase (PD25) [ Time Frame: 1 Year (to measure Adrenergic Antibody assay) ]
    A comparison of the dose of isoproterenol required to acutely increase the Heart Rate by 25 bpm from a pre-injection baseline (as a measure of beta-receptor sensitivity) in antibody positive vs. antibody negative subjects.
  • Phenylephrine Systolic BP Increase (PD25) [ Time Frame: 1 Year (to measure Adrenergic Antibody assay) ]
    A comparison of the dose of phenylephrine required to acutely increase the Systolic Blood Pressure by 25 mmHg from a pre-injection baseline (as a measure of alpha-receptor sensitivity) in antibody positive vs. antibody negative subjects.
  • The proportion of beta adrenergic Ab titer positive subjects [ Time Frame: 1 Year (to measure Adrenergic Antibody assay) ]
    The primary comparison will be the proportion of Ab titers between POTS patients


Original Secondary Outcome: Same as current

Information By: University of Calgary

Dates:
Date Received: January 28, 2016
Date Started: January 2016
Date Completion: December 2022
Last Updated: August 15, 2016
Last Verified: August 2016