Local Vasoconstriction in Postural Tachycardia Syndrome
The investigators study will determine how often blood flow regulation abnormalities and abnormalities of sympathetic regulation produced by nitric oxide, angiotensin-II, and oxidative stress occur in POTS and the mechanism(s) of POTS in individual patients. Specific causes for POTS may vary from patient to patient. Patients will be compared to healthy control subjects. There is a treatment arm with a medication (losartan) that reduces the binding of angiotensin and increases NO. If the investigators know the specific biochemical mechanism the investigators may be able to offer further specific treatments to specific patients.
Postural Tachycardia Syndrome
Drug: Ascorbic Acid (Vitamin C)
Drug: Normal Saline
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Diagnostic
|Official Title:||Local Vasoconstriction in Postural Tachycardia Syndrome|
- Orthostatic tolerance measured by the heart rate and blood pressure response to upright tilt [ Time Frame: 2 months ] [ Designated as safety issue: No ]
- Sympathetic activation and blood flow measured by sympathetic nerve recordings and Doppler blood flow in the leg [ Time Frame: 2 months ] [ Designated as safety issue: No ]
|Study Start Date:||July 2010|
|Estimated Study Completion Date:||June 2015|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
|Active Comparator: Losartan||
Subjects will receive placebo or losartan for 4 weeks. Days 1-7, subjects will receive 12.5mg of Losartan or placebo. Days 7-14, subjects will receive 25mg of Losartan or placebo. Days 14-28, subjects will receive 50mg of Losartan or placebo.
|Active Comparator: Ascorbic Acid (VItamin C)||
Drug: Ascorbic Acid (Vitamin C)
Subjects will receive 60mg/kg of Ascorbic Acid over 20 minutes followed by a maintenance infusion of 20mg/kg.
Other Name: Vitamin C
|Placebo Comparator: Normal Saline||
Drug: Normal Saline
Subjects will receive 60mg/kg of normal saline over 20 minutes followed by a maintenance infusion of 20mg/kg of normal saline.
Chronic orthostatic intolerance due to the postural tachycardia syndrome (POTS) severely impairs daily life in over a million Americans, mostly young women. POTS is defined by symptoms of orthostatic intolerance associated with excessive upright heart rate. While there is general agreement that abnormalities in vascular regulation and autonomic activity account for the tachycardia and symptoms of POTS, its pathophysiology is heterogeneous and only partially characterized.
The key feature of POTS is symptoms which are most prominent when standing. However, in some, findings are present supine (lying down) but worsened standing. Symptoms of POTS include dizziness in all patients, exercise provoked symptoms and thus exercise intolerance, excessive fatigue, nausea and abdominal pain, headache, shortness of breath and deep breathing, weakness, shakiness and postural anxiety, pallor, and neurocognitive loss (difficulty thinking). These occur on a day-to-day basis. The symptoms overlap with the case definition of chronic fatigue syndrome (CFS) and POTS is often found in CFS in the young. Fainting is relatively uncommon during daily life.
A major subset of POTS has increased peripheral resistance and low blood flow(LFP) related to increased angiotensin-II (Ang-II), and decreased nitric oxide (NO). NO deficits are reversed by Ang-II type-1 receptor (AT1R) blockade, ascorbic acid (AA) and tetrahydrobiopterin in skin suggesting the importance of oxidative stress. Preliminary data also suggest that the coupling of sympathetic nerve activity to blood vessel contraction is enhanced via ↑Ang-II and ↓NO. We hypothesize that this is due to activation of reactive oxygen species (ROS) including superoxide, which scavenges NO to generate peroxynitrite, and hydrogen peroxide. Combined measurements in the skin and the systemic circulation will be combined with local measurement of ROS production and sympathetic nerve activity will enable us to determine precisely how the autonomic nervous system is affected by the illness. Methods include cutaneous microdialysis to measure ROS, skin biopsy and blood tests to measure gene expression of nitric oxide synthase and Ang-II receptors, and peroneal microneurography to measure muscle sympathetic nerve activity (MSNA). Combined with ultrasonic femoral artery blood flow this will yield assessment of the interactions of nerves with the blood vessels that they control.
If we discover specific biochemical mechanisms of POTS in patients, then we may be able to specifically treat the defect.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01210430
|Contact: Courtney R Terilli, RN, BSNfirstname.lastname@example.org|
|Contact: Julian M Stewart, MD, PhDemail@example.com|
|United States, New York|
|New York Medical College/Bradhurst building||Recruiting|
|Hawthorne, New York, United States, 10532|
|Contact: Courtney R Terilli, RN, BSN 914-593-8888 firstname.lastname@example.org|
|Contact: Julian M Stewart, MD, PhD 914-593-8888 email@example.com|
|Principal Investigator: Julian M Stewart, MD, PhD|
|Sub-Investigator: Marvin S. Medow, PhD|
|Principal Investigator:||Julian M Stewart, MD, PhD||New York Medical College|