Local Vasoconstriction in Postural Tachycardia Syndrome
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|ClinicalTrials.gov Identifier: NCT01210430|
Recruitment Status : Completed
First Posted : September 28, 2010
Last Update Posted : July 20, 2018
|Condition or disease||Intervention/treatment||Phase|
|Postural Tachycardia Syndrome||Drug: Losartan Drug: Ascorbic Acid (Vitamin C) Drug: Normal Saline||Early Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||74 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Local Vasoconstriction in Postural Tachycardia Syndrome|
|Study Start Date :||July 2010|
|Actual Primary Completion Date :||June 2015|
|Actual Study Completion Date :||June 2015|
|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.
- Orthostatic tolerance measured by the heart rate and blood pressure response to upright tilt [ Time Frame: 2 months ]
- Sympathetic activation and blood flow measured by sympathetic nerve recordings and Doppler blood flow in the leg [ Time Frame: 2 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01210430
|United States, New York|
|New York Medical College/Bradhurst building|
|Hawthorne, New York, United States, 10532|
|Principal Investigator:||Julian M Stewart, MD, PhD||New York Medical College|