Reducing Orthostatic Intolerance With Oral Rehydration in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Cardiology, Infectious Disease, Neurology |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Immunology / Infectious Diseases, Neurology |
| Healthy: | No |
| Age Range: | 15 - 29 |
| Updated: | 1/17/2019 |
| Start Date: | February 2016 |
| End Date: | July 2019 |
Reducing Orthostatic Intolerance With Oral Rehydration in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
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.
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.
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.
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.
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.
We found this trial at
1
site
40 Sunshine Cottage Road
Hawthorne, New York 10532
Hawthorne, New York 10532
Principal Investigator: Marvin S. Medow, Ph.D.
Phone: 914-593-8888
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