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Sponsored by: |
Vanderbilt University |
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Information provided by: | Vanderbilt University |
ClinicalTrials.gov Identifier: | NCT00580619 |
The investigators propose to test the hypothesis that the sympathetic nervous system contributes to the cardiovascular and inflammatory abnormalities present in the chronic fatigue syndrome (CFS) and, in particular in the subset of patients characterized by postural tachycardia syndrome (POTS). CFS and POTS are seen mostly in otherwise normal young women, and are the cause of significant disability. A substantial proportion of patients referred for evaluation of POTS met diagnostic criteria for CFS and, conversely, a subset of patients referred for treatment for CFS have POTS. The investigators hypothesize that sympathetic activation underlies the pathophysiology of patients in whom CFS and POTS overlap (CFS-P).
Condition | Intervention |
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Chronic Fatigue Syndrome Orthostatic Intolerance Postural Tachycardia Syndrome |
Other: Autonomic Function Tests Other: Saline infusions Drug: L-NMMA trimethaphan Drug: methyldopa |
Study Type: | Interventional |
Study Design: | Open Label, Placebo Control, Parallel Assignment, Efficacy Study |
Official Title: | Autonomic Nervous System and Chronic Fatigue Syndrome |
Estimated Enrollment: | 80 |
Study Start Date: | April 2007 |
Estimated Study Completion Date: | December 2012 |
Estimated Primary Completion Date: | December 2012 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Experimental
To evaluate if the various indices of sympathetic activity differ between patients with chronic fatigue syndrome and postural tachycardia syndrome (CFS-P), and CFS without POTS.
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Other: Autonomic Function Tests
The autonomic function tests include asking the subject to breathe deeply for two minutes and breathing as fast and as hard as they can for 30 seconds, maintaining a handgrip for 3 minutes, breathing against pressure for 15 seconds and placing one hand in ice water for 1 minute. All these tests are meant to stimulate the autonomic nervous system to produce changes in blood pressure and heart rate of short duration that reflect how well the involuntary nervous system is working.
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2: Experimental
To test the null hypothesis that there is no difference between two saline therapies (pulse saline vs. sham saline) in improving both the fatigue score and postural tachycardia syndrome.
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Other: Saline infusions
The effects of continuous IV infusion or pulse IV administration of saline in increasing total blood volume and fatigue score will be evaluated
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3: Experimental
Response to nitric oxide inhibition in the presence and absence of an intact autonomic nervous system will be evaluated.
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Drug: L-NMMA trimethaphan
Trimethaphan IV infusion for approximately 60 minutes at a dose of 4-6 mg/min L-NMMA IV infusion for approximately 45 minutes at 125, 250, and 500 mg/kg/min for 15 minutes each
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4: Active Comparator
The effects of chronic autonomic withdrawal on improving symptoms of chronic fatigue and postural tachycardia syndrome will be evaluated
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Drug: methyldopa
Aldomet oral twice a day for 12 weeks
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In Specific Aim 1, the investigators will use state-of-the-art measurements of sympathetic activity (response to trimethaphan, direct nerve sympathetic traffic recordings with microneurography, plasma norepinephrine, and intraneuronal metabolites), inflammatory mediators (C-reactive protein, IL-6), and oxidative stress (isoprostanes) in patients with CFS-P. It is important that appropriate control groups be included, and we will also study patients with CFS without orthostatic tachycardia, patients with POTS without CFS, and normal controls.
The investigators have documented abnormalities in volume regulation in POTS patients. Hypovolemia can contribute to sympathetic activation and, vice versa, sympathetic activation can contribute to hypovolemia. Interrupting this vicious circle with acute saline infusion is the most effective treatment to improve symptoms in POTS patients. Not surprisingly, many POTS patients followed by the investigators, and CFS patients followed by Dr. David Bell, are using saline pulse therapy as a way to alleviate symptoms. However, the efficacy and safety of this approach has not been proven. The investigators propose to validate this treatment in Specific Aim 2. This group studies show that nitric oxide is arguably the most important metabolic factor involved in cardiovascular regulation. Abnormalities in nitric oxide have been proposed to contribute to CFS and POTS, but proving this has been challenging in part due to its interaction with the sympathetic nervous system. In Specific Aim 3, the investigators propose to investigate the importance of nitric oxide in CFS-P patients using an experimental approach developed in our laboratory to eliminate nitric oxide/autonomic interactions.
Finally, in Specific Aim 4, they propose a proof-of-concept study to test the hypothesis that sympathetic activation contributes to many of the abnormalities found in CFS patients. If our hypothesis is correct, inhibition of sympathetic tone will result in improvement of the abnormalities described in volume, inflammation, and oxidative stress. More importantly, it will result in symptomatic improvement in these patients. The investigators believe, therefore, that the studies proposed in this application will improve the understanding of the pathophysiology of CFS, and provide a rationale approach to the treatment of this disabling condition.
Ages Eligible for Study: | 18 Years to 65 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion Criteria:
United States, Tennessee | |
Vanderbilt University Medical Center | Recruiting |
Nashville, Tennessee, United States, 37232 | |
Contact: Ginnie Farley, RA adcresearch@vanderbilt.edu | |
Principal Investigator: Italo Biaggioni, M.D. | |
Sub-Investigator: Alfredo Gamboa, M.D. | |
Sub-Investigator: Luis Okamoto, M.D. | |
Sub-Investigator: Andre Diedrich, M.D., Ph.D | |
Sub-Investigator: Satish Raj, M.D. | |
Sub-Investigator: Bonnie Black, R.N. | |
Sub-Investigator: David Robertson, M.D. | |
Sub-Investigator: Ginnie Farley, RA |
Responsible Party: | Vanderbilt University ( Italo Biaggioni ) |
Study ID Numbers: | 060662, CRC-1636, CRC-1705 |
Study First Received: | December 17, 2007 |
Last Updated: | April 8, 2009 |
ClinicalTrials.gov Identifier: | NCT00580619 History of Changes |
Health Authority: | United States: Institutional Review Board |
Chronic fatigue syndrome Postural tachycardia syndrome Autonomic nervous system |
Vasodilator Agents Neurotransmitter Agents Cholinergic Antagonists Adrenergic Agents Anesthetics Encephalomyelitis Methyldopa Fatigue Syndrome, Chronic Cholinergic Agents Adrenergic Agonists Trimethaphan Signs and Symptoms Trimethaphan camsylate Postural Orthostatic Tachycardia Syndrome Musculoskeletal Diseases |
Neuromuscular Diseases Mental Disorders Orthostatic Intolerance Myalgic Encephalomyelitis Neurocirculatory Asthenia Adrenergic alpha-Agonists Fatigue Heart Diseases Asthenia Tachycardia Adjuvants, Immunologic Central Nervous System Diseases Cardiovascular Agents Antihypertensive Agents Prolapse |
Vasodilator Agents Neurotransmitter Agents Cholinergic Antagonists Molecular Mechanisms of Pharmacological Action Adrenergic Agents Nicotinic Antagonists Physiological Effects of Drugs Encephalomyelitis Methyldopa Fatigue Syndrome, Chronic Cholinergic Agents Adrenergic Agonists Trimethaphan Trimethaphan camsylate Signs and Symptoms |
Pathologic Processes Musculoskeletal Diseases Neuromuscular Diseases Mental Disorders Therapeutic Uses Syndrome Cardiovascular Diseases Neurocirculatory Asthenia Heart Valve Prolapse Ganglionic Blockers Sympatholytics Adrenergic alpha-Agonists Fatigue Heart Diseases Disease |