Autonomic Nervous System and Chronic Fatigue Syndrome

NCT00580619 | Completed Phase 1 DMC

• 3 other identifiers: 060662CRC-1636CRC-1705
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Chronic Fatigue Syndrome; Orthostatic Intolerance; Postural Tachycardia Syndrome

Keywords

Chronic fatigue syndrome; Postural tachycardia syndrome; Autonomic nervous system

Outcome Measures

Primary Outcomes (1)

• Heart rate

  Duration of the intervention

Secondary Outcomes (1)

• Blood Pressure

  Duration of the intervention

Study Arms (4)

1 (markers of sympathetic activity)

EXPERIMENTAL

To evaluate if the various indices of sympathetic activity (Autonomic Function Testing) differ between patients with chronic fatigue syndrome and postural tachycardia syndrome (CFS-P), and CFS without POTS.

Other: Autonomic Function Testing

2 (saline)

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.Saline infusions

Other: Saline infusions

3 (NO inhibition/ autonomic blockade)

EXPERIMENTAL

Response to nitric oxide inhibition in the presence and absence of an intact autonomic nervous system will be evaluated. L-NMMA trimethaphan will be used for NO inhibition and autonomic blockade, respectively.

Drug: L-NMMA trimethaphan

4 (methyldopa)

ACTIVE COMPARATOR

The effects of chronic autonomic withdrawal on improving symptoms of chronic fatigue and postural tachycardia syndrome will be evaluated

Drug: methyldopa

Interventions

Autonomic Function Testing OTHER

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, placing one hand in ice water for 1 minute and an orthostatic test. 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. In addition, a 24-hour blood pressure monitoring and exercise test may be also performed in some subjects.

1 (markers of sympathetic activity)

Saline infusions OTHER

The effects of continuous IV infusion or pulse IV administration of saline in increasing total blood volume and fatigue score will be evaluated

2 (saline)

L-NMMA trimethaphan DRUG

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

3 (NO inhibition/ autonomic blockade)

methyldopa DRUG

Aldomet oral twice a day for 12 weeks

Also known as: Aldomet

4 (methyldopa)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• Okamoto LE, Raj SR, Peltier A, Gamboa A, Shibao C, Diedrich A, Black BK, Robertson D, Biaggioni I. Neurohumoral and haemodynamic profile in postural tachycardia and chronic fatigue syndromes. Clin Sci (Lond). 2012 Feb;122(4):183-92. doi: 10.1042/CS20110200.

  PMID: 21906029 RESULT

MeSH Terms

Conditions

Fatigue Syndrome, Chronic; Orthostatic Intolerance; Postural Orthostatic Tachycardia Syndrome

Interventions

Methyldopa

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Encephalomyelitis; Neuroinflammatory Diseases; Nervous System Diseases; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Primary Dysautonomias; Autonomic Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine

Study Officials

• Italo Biaggioni, MD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine and Pharmacology

Study Record Dates

• First Submitted: December 17, 2007
• First Posted: December 27, 2007
• Study Start: April 1, 2007
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: January 18, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)