Discussion in 'Fibromyalgia Main Forum' started by xchocoholic, Apr 16, 2009.

  1. xchocoholic

    xchocoholic New Member

    I found this and thought some of you might be interested. I'm not sure what the dates of this study are since it's not listed and since I'm too old to qualify, I'll leave it for those who are to call or email them to find out the dates ... It appears to be new though since they say that NO (nitric oxide) may be a cause for OI. Marcia

    PS ... The good news is that we seem to be making a little progress with the testing for this DD ...



    Welcome to the CFS Circulatory Study website. Researchers at the Center for Pediatric Hypotension at New York Medical College in Valhalla NY have received funding from the National Institutes of Health (NIH) to study whether circulatory problems explain the symptoms and signs of the chronic fatigue syndrome in teenagers..

    The Principal Investigator for this study is Julian M. Stewart MD, PhD, Professor of Pediatrics and of Physiology at New York Medical College.

    What comprises the study population?
    What is the hypothesis and importance of the study?
    What are the symptoms and findings in patients?
    What is the goal of the study?
    What your own doctor can do to help diagnose CFS.
    How do I know if I’m eligible to be in this study?
    Who pays for the exams, testing, and travel?
    How can I get a screening application for this study?
    If I decide to participate what does the study entail?

    What comprises the study population?

    We are seeking patients aged 15-29 years old patients with chronic fatigue syndrome (CFS) with or without any overt form of cardiovascular or circulatory disease. While many young people with CFS have a form of overt chronic orthostatic intolerance (the inability to remain upright without symptoms) there are many others who do not. Yet the latter group may still have abnormalities of the small blood vessels, also called microvessels, that are most important in the regulation of blood volume and blood flow. Thus, some of the CFS patients have symptoms of chronic orthostatic intolerance such as dizziness, nausea, headache, pallor, and neurocognitive loss (difficulty thinking) which overlap with the case definition of CFS. Others may not have obvious symptoms while standing but might still have blood vessel abnormalities (i.e. vascular dysfunction) that contribute to fatigue and might benefit from specific therapy.


    What is the hypothesis and importance

    Blood flow abnormalities associated with the postural tachycardia syndrome (POTS) produce major disability in younger chronic fatigue syndrome (CFS) patients. These may be due to defects in a fundamental signaling molecule called nitric oxide (NO) or in its interaction with another molecule called angiotensin. In the current proposal we will determine how NO and angiotensin produce POTS in CFS patients and whether drugs that alter NO and angiotensin can improve patient health.

    We will subset CFS patients by POTS using upright tilt, and subgroup POTS based on noninvasive measurements of peripheral blood flow. Some patients who we denote low flow CFS/POTS have reduced peripheral blood flow, while others have normal flow.
    We will determine whether low flow CFS/POTS is due to decreased NO produced by nNOS and related to increased angiotensin-II (A-II) and oxidative stress. We will measure skin blood flow with lasers, and NO and angiotensin by intradermal microdialysis tiny tubes in the skin), and use local heating and chemical responses in the skin to a commonly used blocker of angiotensin called losartan. If losartan works in the skin we will try to treat low blood flow with oral losartan and measure the extent of improvement in blood flow throughout your body.

    Data suggest that NO is increased in normal flow CFS/POTS at least in the gut circulation causing pooling of blood during upright posture. We will determine whether this is true in the skin. If this is true in the skin, we will test whether a systemic medication called octreotide reduces orthostatic gut blood pooling and cutaneous microvascular NO dependent responses.

    What are the symptoms of CFS with POTS

    Fainting is uncommon. Symptoms of CFS/POTS and chronic orthostatic intolerance including dizziness, fatigue, nausea and abdominal pain, headache, pallor, and neurocognitive loss (difficulty thinking), shakiness and exercise intolerance which overlap with the case definition of CFS. Most of the time these symptoms are postural, present mostly when upright or standing and relieved by lying down.


    What is the goal of the study

    The overall objective of the current application is to determine the biochemical mechanisms of CFS/POTS as they relate to changes in NO and angiotensin, and to explore the possibility of subclinical, microvascular abnormalities in those CFS patients without POTS. If POTS is present we will also test medications used for treating POTS which may help teenagers with CFS.


    What can your own doctor do

    Your doctor can rule out other illnesses such as infectious and inflammatory conditions which can produce similar symptoms. For example, most blood tests will be performed by your own physician. However, the tests we will be performing are not ordinarily available to your doctor. They are, however, all approved ways of measuring how blood vessels work. POTS can be treated by a combination of lifestyle adjustments and medication which your doctor can administer. The tests performed during the study may help us determine what treatment is best for you. We will provide you and your doctor with test results and treatment information.


    How do I know if I’m eligible to be in this study?

    Even though the study focuses on CFS patients with vascular dysfunction, all CFS patients should enroll. At this time we cannot predict who has circulatory dysfunction or if POTS is the only form of orthostatic intolerance in young persons with CFS. Therefore all patients who fulfill the criteria for CFS (using the 1994 Centers for Disease Control definition) and are between 15 and 29 years old can enroll.

    The diagnosis of CFS should be made by a doctor, either your own physician or through contact with our center.

    Exclusion:The criteria for initial exclusion are adapted from the CDC and include: 1) an active medical condition that may explain the diagnosis; 2) a previous medical condition with undocumented resolution; 3) a past or current major psychiatric disorder; 4) a history of alcohol or substance abuse within 2 years before the onset of the chronic fatigue.

    Inclusion: The criteria for initial inclusion are adapted from the CDC:15 and 29 years old adolescents who have persistent or relapsing chronic fatigue of new or definite onset; and the concurrent occurrence of four or more of the following symptoms that have persisted or recurred during at least 6 consecutive months and have not predated the fatigue:
    1) impairment in memory or concentration severe enough to cause substantial reduction of previous levels of educational, social or personal activities. In adolescents this may be most notable by a decline in academic performance and school attendance;
    2) muscle pain or multi joint pain;
    3) headaches of a new type, pattern, or severity;
    4) unrefreshing sleep; and
    5) post-exertional malaise lasting more than 24 hours.

    Sore throat and swollen glands are unreliable criteria during adolescence .


    Who pays for the exams, or testing?

    There is no charge to you for any of the the testing or testing medication. We will pay each participant who $300 as a token of appreciation for their time.


    How can I get a screening application for this study?

    You can click on the Screening icon, and download and print out the application and mail it to us. The mailing address is on the last page of the form. Alternatively you can email the application to courtney_terilli@nymc.edu or to stewart@nymc.edu or you can also fax us the application at 914-593-8888. Or, you can call us at 914-593-8888, leave your name and address on the voicemail and we’ll mail you an application.


    What happens if I’m eligible to be in the study and decide to participate?

    If you would like to take part in this study, Courtney Terilli, our nurse research coordinator, will contact you to go over questionnaire material and discuss arranging for the study. The study nurse will review the consent form with you and we will also review the consent and any questions you may have when you arrive for the study. You and your parents should understand the study, and its risks and benefits. You can click on the icon for Consent Form to read about our study. If it is at all possible patients should not be taking medications that could affect the results. These might include beta blockers, fludrocortisone, and other medications that affect blood vessel or cardiac function. You must work with your doctor to see if this is safe to do and to determine how it is best accomplished.

    Testing will last 2 days. We will make an appointment to come to The Center for Hypotension for your study visits. You’ll arrive at 9:00-10 AM on the first day of your appointment. We ask that you not eat or drink anything after 8 AM that morning. Please wear comfortable clothing and bring along a pair of shorts and a short sleeve shirt.

    We will meet you at the Bradhurst Building and take you to the laboratory area. Here the you will meet Drs. Stewart, Taneja and Medow who, along with the nurse, will review the study with you, and answer any questions you may have. After obtaining your or your parents informed consent , you’ll be taken to the laboratory area.

    Patients will undergo most studies of blood flow while lying down. A tilt test may be necessary on the first day of testing. Medication will be administered on the second day of testing and responses assessed while lying down and during a sshort tilt test. Tilt tests will last a maximum of 10 minutes and will involve no faint-provoking medications. Simple tests of how the nervous system adjusts to changes in circulation will also be performed. We will also measure blood hormone levels. Most likely you will be asked to have a measurement of blood volume using the FDA approved Daxor method which can be done near your home.

    If medication appears to have an acute benefit we will issue a prescription for home use.

    We believe that this study will help to determine the specific cause of POTS in CFS and will point towards improved medical therapy for younger CFS patients.

    We expect that each visit will last about 6 hours.

    If you have further questions about the study, please feel free to call:
    914-593-8888 for more information.
    or Email courtney_terilli@nymc.edu.

    [This Message was Edited on 04/16/2009]
  2. xchocoholic

    xchocoholic New Member


    Defining Characteristics

    Orthostasis = standing upright. Orthostatic intolerance can then be defined as "the development of symptoms during upright standing relieved by recumbency".

    Often, illnesses producing orthostatic intolerance include disorders of blood flow, heart rate and blood pressure regulation that, while most easily demonstrable during orthostatic stress, are present in all positions.

    The term "dysautonomia", signifying autonomic dysfunction, has been frequently applied to this list of disorders, but recent data suggest that autonomic function may be normal in many variants of these conditions but have to cope with unusual circulatory demands.

    A simple and common example of this is the finding of postural hypotension and postural tachycardia when dehydrated. Therefore it is probably best to denote the type of symptomatic illness by the more vague term "orthostatic intolerance" rather than the more specific term"dysautonomia" which may not be correct.

    Acute orthostatic intolerance usually manifests as syncope (fainting). Many syncopal patients have no intercurrent illness; between faints they are well.

    Chronic orthostatic intolerance implies day-to-day symptoms including dizziness in all patients, and often altered vision (blurred, ‘white outs’, ‘black-outs’), fatigue, nausea, neurocognitive deficits, disordered thermoregulation, palpitations, headache, tremulousness, hyperpnea, difficulty breathing, sweating, and pallor.

    These produce day-to-day disability; estimates suggest that over a million Americans are affected, mostly young women, who may be prevented from gainful employ or school attendance.

    Chronic orthostatic intolerance is associated with postural tachycardia syndrome (POTS). When symptoms of chronic orthostatic intolerance are present, signs of POTS are almost always found.

    Most forms of orthostatic intolerance are not typically life threatening although circumstances can conspire to create considerable risk.

    Evidence suggests that the changes in heart rate, blood pressure, and cerebral blood flow that produce orthostatic intolerance may be related to abnormalities in the interplay between blood volume control, the cardiovascular system, the autonomic nervous system and local circulatory mechanisms that regulate these basic physiological functions.

    Therefore, the control of the circulatory system should be considered neurovascular, resulting from the interactions between neurological and cardiovascular systems.

    These interactions, may alter blood flow through direct effects on blood pressure, by redistribution of blood flow resulting in altered blood return to the heart and drastic reductions in the amount of blood that the heart can pump (cardiac output), and by local flow regulatory mechanisms that impair cerebral blood flow .

    This results in decreases in blood flow to the skin and muscles producing pallor, and decreases in blood flow to the brain producing light-headedness or loss of consciousness although respiratory changes may produce hypocapnea and cerebral vasoconstriction that precedes changes in blood pressure.

    This rather striking hyperpnea and associated dyspnea may even be produced in healthy volunteer subjects and is often observed prior to overt circulatory failure in fainting and chronic orthostatic intolerance.

    Separate evidence also indicates the potential for abnormal central nervous system autoregulation which normally spares the brain from the consequences of low flow states.

    While there is often evidence for impaired neurovascular interactions while supine, orthostasis (standing up) profoundly stresses the control mechanisms.

    Thus symptoms of neurovascular regulatory failure are often first appreciated during orthostatic challenge analogous to the use of exercise as a challenge to aerobic conditioning and during heart failure.

    Therefore, while neurovascular abnormalities can be assessed supine and often noninvasively, orthostatic stress testing (analogous to exercise stress testing) is frequently employed.

    While standing may be the most physiological orthostatic stressor, head-up tilt table testing (HUT), has become the standard stress test for orthostatic integrity and thus of neurovascular regulatory competence.

    In addition a research procedure called lower body negative pressure may provide physiological challenges which in many respects emulate and complement orthostatic stress.

    However, most laboratories use upright tilt to diagnose syncope and other orthostatic disability.

    The test is simple - using a motorized table with a foot support to raise the patient from supine to approximately 60-70 degrees upright without the use of the patient's own muscles.

    At the Center for Pediatric Hypotension we perform research using supine and upright measurements of neurovascular integrity.

    Often these combine Orthostatic stress testing and instrumentation designed to measure circulatory and orthostatic compensatory activity.

    These include determinations of , heart rate and blood pressure variability, baroreflex assessment, autonomic assessment, peripheral and central measures of blood flow, vascular capacitance, and permeability properties to obtain information concerning the physiology and thus relative risk for fainting and OI in vulnerable patients and in healthy volunteer control subjects.

    Patterns of blood pressure and heart rate during HUT take diverse forms which relate to the underlying mechanism of disease and which may help individualize specific therapy.

    Patients with orthostatic intolerance diagnosed by these techniques can often be helped by medical therapy or other forms of intervention.

    Many of such patients have received little effective therapy for their problems and some have received treatment for diseases (such as seizure disorders) which they do not have.

    In both instances appropriate use of tilt-testing, autonomic assessment, and vascular integrity may both specify and simplify their therapy.

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