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Reducing Orthostatic Intolerance With Oral Rehydration in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

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ClinicalTrials.gov Identifier: NCT02854683
Recruitment Status : Active, not recruiting
First Posted : August 3, 2016
Last Update Posted : July 19, 2018
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
New York Medical College

Brief Summary:
We and others have shown that many younger patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) have orthostatic intolerance (OI), i.e., they can't tolerate prolonged standing. OI in ME/CFS is often accompanied by either postural tachycardia syndrome (POTS) in which standing results in an excessive heart rate, and neurally mediated hypotension (NMH) in which standing causes a fall in blood pressure and fainting. Intravenous fluids can alleviate these symptoms, but is difficult to administer; oral fluids fail to provide the same benefit. We would therefore like to test the effectiveness of an oral rehydration solution (ORS, W.H.O. formula) making use of co-transport of glucose and sodium, to reverse these symptoms in ME/CFS subjects with POTS or NMS, and will compare these results with healthy control subjects.

Condition or disease Intervention/treatment Phase
Chronic Fatigue Syndrome Myalgic Encephalomyelitis Systemic Exertion Intolerance Disease (SEID) Postural Tachycardia Syndrome (POTS) Neurally Mediated Syncope (NMS) Drug: Normal Saline Dietary Supplement: Oral Rehydration Solution Phase 1

Detailed Description:
We and others have shown that a majority of younger patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) have orthostatic intolerance (OI), the inability to tolerate orthostatic stress such as prolonged standing. OI in ME/CFS comprises postural tachycardia syndrome (POTS) in which symptoms occur along with excessive upright heart rate, and neurally mediated hypotension (NMH) in which symptoms occur along with an upright fall in blood pressure. The causes of OI are diverse but are clearly initiated by postural contraction of central blood volume (BV) by gravitational translocation of 500-800 mL of blood from the upper to the lower body. Intravenous central BV expansion with isotonic saline is commonly and effectively used to reduce OI regardless of etiology, but has complications if used long term. Usual forms of oral hydration fail to provide similar benefit. Interestingly, a specific isotonic oral rehydration solution (ORS W.H.O. formula), making use of co-transport of glucose and sodium, has been shown to efficiently rehydrate cholera patients suggesting an ability to increase central BV rivaling intravenous fluids. Since the circulatory effects of saline or ORS BV expansion are incompletely understood, we propose to study the neurovascular physiology of fluid loading during orthostatic stress in ME/CFS patients with POTS or NMH, comparing results with healthy control subjects. We hypothesize that equal volumes of ORS is not inferior and may be superior to intravenous saline infusion in increasing intravascular and interstitial fluid volume and improving orthostatic tolerance. Using noninvasive measurements of heart rate and blood pressure by Finapres and oscillometry, cardiac output and peripheral arterial resistance by inert gas rebreathing, cerebral blood flow velocity by transcranial Doppler ultrasound, and regional fluid shifts by impedance and venous occlusion plethysmography, we have acquired preliminary data in ME/CFS patients with OI demonstrating superior restoration of orthostatic tolerance with ORS. We will recruit patients aged 15-29 years who have confirmed ME/CFS with OI, including 15 with NMH and 15 with POTS, and compare them to 15 healthy volunteer subjects. In Specific Aim 1 we will measure BV by Daxor iodinated albumin technique before orthostatic stress imposed by step-wise lower body negative pressure (LBNP) to measure the threshold for OI. Relative changes in BV using serial hematocrits in OI patients will be compared to data from control subjects similarly tested. In Specific Aim 2, all subjects will be randomized to receive saline or ORS in a cross over study. On one day, total BV and neurovascular properties will be measured in patients and control subjects before and 1 hour after completing one liter administration of intravenous normal saline infusion or ORS. On another day (separated by 1 week), we will repeat measurements using the other hydration route. We will perform LBNP on each day following saline or ORS to determine whether orthostatic intolerance and circulatory physiology are improved similarly with equivolumic IV saline or ORS hydration.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Reducing Orthostatic Intolerance With Oral Rehydration in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Study Start Date : February 2016
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : January 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Normal Saline
Subjects will receive 1 liter of intravenous normal saline over 1 hour and on an alternate day Subjects will drink ORS solution 1 liter total by mouth over 20 minutes.
Drug: Normal Saline
1 liter of intravenous saline will be delivered over 1 hour
Other Name: NSS

Experimental: Oral rehydration solution
Subjects will receive 1 liter of intravenous normal saline over 1 hour and on an alternate day Subjects will drink ORS solution 1 liter total by mouth over 20 minutes.
Dietary Supplement: Oral Rehydration Solution
1 liter of ORS solution given by mouth
Other Name: ORS




Primary Outcome Measures :
  1. To test whether 1 Liter volumes of intravenous or oral rehydration solution increase total blood volume and cardiac output, comparably improving the threshold for orthostatic intolerance [ Time Frame: 1 week ]
    We will measure total blood volume, cardiorespiratory properties, plasma osmolarity and electrolytes before and after 1 hour after completing an intravenous infusion of normal saline. Hematocrit will be measure every 10 minutes for changes in blood volume. On a second day, we will measure total blood volume, cardiorespiratory properties, plasma osmolarity and electrolytes before and after 1 hour after ingesting 1 liter of oral rehydration solution. Hematocrit will be measure every 10 minutes for changes in blood volume.



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Ages Eligible for Study:   15 Years to 29 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Both female and male participants are being studies
  • Ages 15-29
  • All subjects must fulfill criteria for Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) and include 15 with Neurally Mediated Syncope (NMS) and 15 with Postural Tachycardia Syndrome (POTS).
  • ME/CFS patients with NMS will be cases with episodic symptoms of Orthostatic Intolerance (OI) associated with 3 or more episodes of abrupt loss of consciousness and postural tone within the last year (simple faint)
  • ME/CFS patients with POTS will have chronic day to day symptoms of OI for at least 3 months. POTS will be confirmed by duplication of these symptoms per tilt table test
  • Healthy volunteers will be included and free from any disease

Exclusion Criteria:

  • all subjects will have normal physical exam and be free of all systemic disease
  • no subjects will be taking neurally active or vasoactive medications. Any prior medications will be discontinued for at least 2 weeks.

Information from the National Library of Medicine

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): NCT02854683


Locations
United States, New York
NewYork Medical College
Hawthorne, New York, United States, 10532
Sponsors and Collaborators
New York Medical College
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Principal Investigator: Marvin S. Medow, Ph.D. New York Medical Collete

Additional Information:
Responsible Party: New York Medical College
ClinicalTrials.gov Identifier: NCT02854683     History of Changes
Other Study ID Numbers: L-11-531-101
1R21NS094644-01 ( U.S. NIH Grant/Contract )
First Posted: August 3, 2016    Key Record Dates
Last Update Posted: July 19, 2018
Last Verified: July 2018

Keywords provided by New York Medical College:
Chronic Fatigue Syndrome (CFS)
Myalgic Encephalomyelitis (ME)
Postural Tachycardia Syndrome (POTS)
Neurally Mediated Syncope (NMS)
Systemic Exertion Intolerance Disease (SEID)
Orthostatic Intolerance (OI)
Oral Rehydration Solution (ORS)
Lower Body Negative Pressure (LBNP)

Additional relevant MeSH terms:
Syndrome
Tachycardia
Fatigue Syndrome, Chronic
Postural Orthostatic Tachycardia Syndrome
Fatigue
Syncope
Encephalomyelitis
Orthostatic Intolerance
Myalgia
Syncope, Vasovagal
Disease
Pathologic Processes
Signs and Symptoms
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Unconsciousness
Consciousness Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Virus Diseases
Muscular Diseases
Musculoskeletal Diseases
Central Nervous System Diseases
Neuromuscular Diseases
Primary Dysautonomias
Autonomic Nervous System Diseases
Central Nervous System Infections
Musculoskeletal Pain