NIH URL
This study is currently recruiting participants.
Verified by Vanderbilt University, April 2009
First Received: December 17, 2007 Last Updated: April 8, 2009 History of Changes
Sponsored by:Vanderbilt University
Information provided by:Vanderbilt University
ClinicalTrials.gov Identifier:NCT00580619
Purpose
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).
ConditionIntervention
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
Resource links provided by NLM:
Genetics Home Reference related topics: Brugada syndrome short QT syndrome
MedlinePlus related topics: Chronic Fatigue Syndrome Marijuana Mitral Valve Prolapse Mobility Aids
Drug Information available for: Trimethaphan camsylate omega-N-Methylarginine Methyldopa Methyldopa ethyl ester hydrochloride Methyldopate Trimethaphan
U.S. FDA Resources
Further study details as provided by Vanderbilt University:
Primary Outcome Measures:
Heart rate [ Time Frame: Duration of the intervention ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
Blood Pressure [ Time Frame: Duration of the intervention ] [ Designated as safety issue: No ]
Estimated Enrollment:80
Study Start Date:April 2007
Estimated Study Completion Date
ecember 2012
Estimated Primary Completion Dateecember 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
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.
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
3: Experimental
Response to nitric oxide inhibition in the presence and absence of an intact autonomic nervous system will be evaluated.
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
4: Active Comparator
The effects of chronic autonomic withdrawal on improving symptoms of chronic fatigue and postural tachycardia syndrome will be evaluated
Drug: methyldopa
Aldomet oral twice a day for 12 weeks
Detailed Description:
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.
Eligibility
Ages Eligible for Study: 18 Years to 65 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: Yes
Criteria
Inclusion Criteria:
Meet CDC diagnostic criteria of CFS (Fukuda et al., 1994)
Meet diagnostic criteria of POTS (Raj et al., 2005)
Age between 18-65 years
Male and female are eligible (although the majority of patients with CFS-P are female)
Exclusion Criteria:
Presence of medical conditions that can explain postural tachycardia syndrome (e.g., dehydration, medications)
Presence of medical or psychiatric conditions known to cause fatigue (Fukuda et al., 1994). Inability to give, or withdrawal of, informed consent
Inability to acquire or maintain adequate long-term intravenous access (peripheral indwelling catheter, PIC)
Pregnancy
Other factors which in the investigator's opinion would prevent the subject from completing the protocol
Patients who are bedridden or chair-ridden
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00580619
Locations
United States, Tennessee
Vanderbilt University Medical CenterRecruiting
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
.
This study is currently recruiting participants.
Verified by Vanderbilt University, April 2009
First Received: December 17, 2007 Last Updated: April 8, 2009 History of Changes
Sponsored by:Vanderbilt University
Information provided by:Vanderbilt University
ClinicalTrials.gov Identifier:NCT00580619
Purpose
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).
ConditionIntervention
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
Resource links provided by NLM:
Genetics Home Reference related topics: Brugada syndrome short QT syndrome
MedlinePlus related topics: Chronic Fatigue Syndrome Marijuana Mitral Valve Prolapse Mobility Aids
Drug Information available for: Trimethaphan camsylate omega-N-Methylarginine Methyldopa Methyldopa ethyl ester hydrochloride Methyldopate Trimethaphan
U.S. FDA Resources
Further study details as provided by Vanderbilt University:
Primary Outcome Measures:
Heart rate [ Time Frame: Duration of the intervention ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
Blood Pressure [ Time Frame: Duration of the intervention ] [ Designated as safety issue: No ]
Estimated Enrollment:80
Study Start Date:April 2007
Estimated Study Completion Date
ecember 2012Estimated Primary Completion Date
ecember 2012 (Final data collection date for primary outcome measure)Arms Assigned Interventions
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.
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.
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.
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
3: Experimental
Response to nitric oxide inhibition in the presence and absence of an intact autonomic nervous system will be evaluated.
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
4: Active Comparator
The effects of chronic autonomic withdrawal on improving symptoms of chronic fatigue and postural tachycardia syndrome will be evaluated
Drug: methyldopa
Aldomet oral twice a day for 12 weeks
Detailed Description:
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.
Eligibility
Ages Eligible for Study: 18 Years to 65 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: Yes
Criteria
Inclusion Criteria:
Meet CDC diagnostic criteria of CFS (Fukuda et al., 1994)
Meet diagnostic criteria of POTS (Raj et al., 2005)
Age between 18-65 years
Male and female are eligible (although the majority of patients with CFS-P are female)
Exclusion Criteria:
Presence of medical conditions that can explain postural tachycardia syndrome (e.g., dehydration, medications)
Presence of medical or psychiatric conditions known to cause fatigue (Fukuda et al., 1994). Inability to give, or withdrawal of, informed consent
Inability to acquire or maintain adequate long-term intravenous access (peripheral indwelling catheter, PIC)
Pregnancy
Other factors which in the investigator's opinion would prevent the subject from completing the protocol
Patients who are bedridden or chair-ridden
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00580619
Locations
United States, Tennessee
Vanderbilt University Medical CenterRecruiting
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
.
