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Local Vasoconstriction in Postural Tachycardia Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by New York Medical College
Sponsor:
Information provided by (Responsible Party):
Julian Stewart, New York Medical College
ClinicalTrials.gov Identifier:
NCT01210430
First received: August 19, 2010
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Postural Tachycardia Syndrome
Drug: Losartan
Drug: Ascorbic Acid (Vitamin C)
Drug: Normal Saline
Phase 0

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by New York Medical College:

Primary Outcome Measures:
  • Orthostatic tolerance measured by the heart rate and blood pressure response to upright tilt [ Time Frame: 2 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 90
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)
Arms Assigned Interventions
Active Comparator: Losartan Drug: 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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   14 Years to 29 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Cases will be between the ages of 14 and 29 years old referred for evaluation of orthostatic intolerance with 3 or more of the following symptoms for at least 3 months:

    • dizziness
    • nausea and vomiting
    • palpitations
    • fatigue
    • headache
    • exercise intolerance
    • blurred vision
    • abnormal sweating heat.
  • Cases will have the diagnosis of symptomatic postural tachycardia made during a screening tilt table test.
  • Cases will have normal physical examination, and normal electrocardiographic and echocardiographic evaluations.
  • Only those free from heart disease, and from systemic illness will be eligible to participate.
  • This excludes patients with illnesses and disease states known to be associated with endothelial cell dysfunction such as diabetes, renal disease, congestive heart failure, systemic hypertension, acute and chronic inflammatory diseases, neoplasm, immune mediated disease, trauma, morbid obesity and peripheral vascular disease.
  • At the time of testing all patients and control subjects must refrain from vasoactive drugs for two weeks. Please check with us about any medication that you are taking.

Exclusion Criteria:

  • Criteria for initial exclusion will include a condition known to be associated with endothelial dysfunction
  • An active medical condition that may explain the diagnosis
  • A previous medical condition with undocumented resolution that may explain the diagnosis
  • Past or present major psychiatric disorder
  • Substance abuse within 2 years before onset of symptoms.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01210430

Contacts
Contact: Courtney R Terilli, RN, BSN 914-593-8888 courtney_terilli@nymc.edu
Contact: Julian M Stewart, MD, PhD 914-593-8888 julian_stewart@nymc.edu

Locations
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    courtney_terilli@nymc.edu   
Contact: Julian M Stewart, MD, PhD    914-593-8888    julian_stewart@nymc.edu   
Principal Investigator: Julian M Stewart, MD, PhD         
Sub-Investigator: Marvin S. Medow, PhD         
Sponsors and Collaborators
New York Medical College
Investigators
Principal Investigator: Julian M Stewart, MD, PhD New York Medical College
  More Information

Additional Information:
No publications provided

Responsible Party: Julian Stewart, Professor of Pediatrics, New York Medical College
ClinicalTrials.gov Identifier: NCT01210430     History of Changes
Other Study ID Numbers: 2 R01 HL074873-06A2
Study First Received: August 19, 2010
Last Updated: July 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by New York Medical College:
Ascorbic Acid
Vitamin C
Postural Tachycardia Syndrome
Orthostatic Intolerance
Reactive Oxygen Species
Oxidative Stress
Angiotensin II
Nitric Oxide
Blood Flow
POTS
Losartan

Additional relevant MeSH terms:
Ascorbic Acid
Postural Orthostatic Tachycardia Syndrome
Syndrome
Tachycardia
Arrhythmias, Cardiac
Autonomic Nervous System Diseases
Cardiovascular Diseases
Disease
Heart Diseases
Nervous System Diseases
Orthostatic Intolerance
Pathologic Processes
Primary Dysautonomias
Losartan
Vitamins
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Anti-Arrhythmia Agents
Antihypertensive Agents
Antioxidants
Cardiovascular Agents
Growth Substances
Micronutrients
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014