Noradrenergic and Stress-Related Etiologies of Chronic Fatigue Syndrome

NCT03029377 | Completed

• 1 other identifier: 161423
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to measure sympathetic nervous system function and stress responses in patients with clinically documented and self-reported chronic fatigue that is worsened by stress, compared to healthy controls. Baseline norepinephrine (NE) levels and stress-induced NE levels in patients who fulfill criteria for Chronic Fatigue Syndrome (CFS) and who self-identify with stress induced worsening fatigue, will be compared to data from normal individuals pre and post-stress.

Conditions

Chronic Fatigue Syndrome

Keywords

CFS; Stress; Norepinephrine Transporter (NET); Norepinephrine (NE); Healthy Controls; Fatigue

Outcome Measures

Primary Outcomes (1)

• dihydroxyphenylglycol (DHPG)/norepinephrine (NE) Ratio (post stress)

  Change in DHPG/NE Ratio from Baseline to post stress compared across arms

  Change from Baseline to post stress test (approximately 100 minutes post-baseline blood collection)

Secondary Outcomes (12)

• DHPG/NE Ratio (post Autonomic Function test)

  Change from Baseline to post Autonomic Function test (approximately 30 minutes post-baseline blood collection)

• DHPG/NE Ratio (post Standing position)

  Change from Baseline to post Standing position (approximately 40 minutes post-baseline blood collection)

• DHPG/NE Ratio (post Sitting position)

  Change from Baseline to post Sitting position (approximately 70 minutes post-baseline blood collection)

• Absolute DHPG and NE Levels (post stress)

  Change from Baseline to post stress test (approximately 100 minutes post-baseline blood collection)

• Absolute DHPG and NE Levels (post Autonomic Function test)

  Change from Baseline to post Autonomic Function test (approximately 30 minutes post-baseline blood collection)

Study Arms (2)

Chronic Fatigue Patients

EXPERIMENTAL

Patients between 18-60 years of age with fatigue symptoms who meet preliminary chronic fatigue phenotype criteria and complete preliminary screening surveys. Participants will undergo a Posture Study, Autonomic Function Tests, and a Stress Test. Participants' blood will be drawn to measure markers of sympathetic nervous system function.

Other: Posture Study, Autonomic Function Tests, and a Stress Test

Healthy Controls

ACTIVE COMPARATOR

Patients between 18-60 years of age with no known conditions or prescription medications who meet preliminary screening criteria. Participants will undergo a Posture Study, Autonomic Function Tests, and a Stress Test. Participants' blood will be drawn to measure markers of sympathetic nervous system function.

Other: Posture Study, Autonomic Function Tests, and a Stress Test

Interventions

Posture Study, Autonomic Function Tests, and a Stress Test OTHER

Participants will undergo a Posture Study, Autonomic Function Tests, and a Stress Test. Participants' blood will be drawn to measure markers of sympathetic nervous system function at baseline, in three postural positions, after autonomic tests, and after a stress test.

Chronic Fatigue Patients; Healthy Controls

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Confirmed chronic fatigue with severity \>50 on a scale of 1 to 100 that is not improving over time
• Meet The Centers for Disease Control and Prevention (CDC) diagnostic criteria of CFS (self-reported persistent or relapsing fatigue lasting 6 or more consecutive months)

You may not qualify if:

• Male and female subjects \<18 or \>60 years
• Obesity, defined as a BMI of 30 or more
• Presence of other medical or psychiatric conditions known to cause fatigue (alcohol/drug abuse, anorexia nervosa, bipolar disorder, bulimia nervosa, dementia, major depression, psychotic/delusional disorders, schizophrenia)
• Presence of sleep disorder/disruption known to cause fatigue (sleep apnea, narcolepsy)
• Cardiovascular, pulmonary, hepatic, or hematological disease by history or prior testing defined as significant by investigator (including but not limited to chronic hepatitis, chronic kidney disease, cirrhosis, emphysema, heart failure, HIV, lupus, multiple sclerosis, myasthenia gravis, rheumatoid arthritis)
• History of hypertension defined as supine resting BP\>145/95 mmHg off medications or needing antihypertensive medication
• Patients taking medications that can affect autonomic function or plasma catecholamines (vasoactive drugs), stimulants, and/or are sedatives
• Other factors which in the opinion of the investigator could potentially impact the study outcomes (e.g., underlying disease, medications, history)\* or prevent the participant from completing the protocol (poor compliance or unpredictable schedule)
• Inability to stand unassisted for 10 minutes
• Patients who are bedridden or chair-ridden
• Patients who are colorblind
• Inability or refusal to give informed consent for any reason including a diagnosis of dementia or cognitive impairment
• Patients who are pregnant or breastfeeding
• Healthy Control Participants:
• Participant with no significant reported conditions or medications.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37203, United States

Location

Related Publications (3)

• 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 BACKGROUND

• Shirey-Rice JK, Klar R, Fentress HM, Redmon SN, Sabb TR, Krueger JJ, Wallace NM, Appalsamy M, Finney C, Lonce S, Diedrich A, Hahn MK. Norepinephrine transporter variant A457P knock-in mice display key features of human postural orthostatic tachycardia syndrome. Dis Model Mech. 2013 Jul;6(4):1001-11. doi: 10.1242/dmm.012203. Epub 2013 Apr 4.

  PMID: 23580201 BACKGROUND

• Danciu I, Cowan JD, Basford M, Wang X, Saip A, Osgood S, Shirey-Rice J, Kirby J, Harris PA. Secondary use of clinical data: the Vanderbilt approach. J Biomed Inform. 2014 Dec;52:28-35. doi: 10.1016/j.jbi.2014.02.003. Epub 2014 Feb 14.

  PMID: 24534443 BACKGROUND

Related Links

• CDC - Chronic Fatigue Syndrome (CFS)

MeSH Terms

Conditions

Fatigue Syndrome, Chronic; Fatigue

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; Signs and Symptoms

Study Officials

• Gordon Bernard, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Executive Vice President for Research

Study Record Dates

• First Submitted: January 9, 2017
• First Posted: January 24, 2017
• Study Start: January 1, 2017
• Primary Completion: February 23, 2018
• Study Completion: February 23, 2018
• Last Updated: April 26, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)