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Myalgic Encephalomyelitis Chronic Fatigue at the National Institutes of Health

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02669212
Recruitment Status : Completed
First Posted : February 1, 2016
Results First Posted : April 18, 2023
Last Update Posted : April 18, 2023
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Screening
Condition Chronic Fatigue Syndrome
Intervention Behavioral: Cardiopulmonary Exercise Test (CPET)
Enrollment 52
Recruitment Details Participants were either referred to study investigators by their primary care physician or were self-referred either through the Patient Recruitment and Public Liaison (PRPL) office or direct contact. Interested participants were contacted by telephone to evaluate eligibility. Eligible participants were subsequently seen at the NIH Clinical Center for study visits. Recruitment began February 2016 and ended February 2020.
Pre-assignment Details Participants underwent telephone screening followed by a medical record review/discussion with the participant's physician to determine general eligibility. Participants were invited to campus to determine if they met inclusion/exclusion criteria for the phenotyping phase of the study. After the phenotyping visit, results were reviewed by a panel of expert adjudicators to determine case status and eligibility for the exercise phase of the protocol. No Lyme disease participants were recruited.
Arm/Group Title Healthy Volunteer Participants ME/CFS Participants
Hide Arm/Group Description Participants found to be healthy after a medical and psychiatric evaluation. Participants with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Period Title: Overall Study
Started 25 27
Completed 21 17
Not Completed 4 10
Reason Not Completed
Lost to Follow-up             1             0
Medical Condition             3             4
Withdrawal by Subject             0             2
Excluded - determined NOT post-infectious             0             4
Arm/Group Title Healthy Volunteer Participants ME/CFS Participants Total
Hide Arm/Group Description Participants found to be healthy after a medical and psychiatric evaluation. Participants with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Total of all reporting groups
Overall Number of Baseline Participants 25 27 52
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 27 participants 52 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
25
 100.0%
27
 100.0%
52
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 25 participants 27 participants 52 participants
42.24  (13.46) 37.82  (14.72) 40.35  (13.48)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 27 participants 52 participants
Female
13
  52.0%
13
  48.1%
26
  50.0%
Male
12
  48.0%
14
  51.9%
26
  50.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 27 participants 52 participants
Hispanic or Latino
2
   8.0%
2
   7.4%
4
   7.7%
Not Hispanic or Latino
23
  92.0%
25
  92.6%
48
  92.3%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 27 participants 52 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
2
   7.4%
2
   3.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   4.0%
0
   0.0%
1
   1.9%
White
21
  84.0%
25
  92.6%
46
  88.5%
More than one race
3
  12.0%
0
   0.0%
3
   5.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Cardiopulmonary Exercise Test (CPET) - ATVO2rel
Hide Description The Relative Volume of Oxygen at the Anaerobic Threshold (ATVO2rel) was determined during a cardiopulmonary exercise test (CPET). ATVO2rel represents the volume of oxygen being consumed when a participant reaches AT, adjusted for their weight during the CPET. Results compared Healthy Volunteer Participants to ME/CFS Participants.
Time Frame At time of AT during CPET
Hide Outcome Measure Data
Hide Analysis Population Description
COVID-19 pandemic halted return visit for participation in Exercise Phase of trial.
Arm/Group Title Healthy Volunteers ME/CFS Participants
Hide Arm/Group Description:
Participants found to be healthy after a medical and psychiatric evaluation who completed the Cardiopulmonary Exercise Test (CPET).
ME/CFS Participants who complete the Cardiopulmonary Exercise Test (CPET)
Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: mL/kg/min
16.0  (4.3) 10.6  (3.8)
2.Primary Outcome
Title Cardiopulmonary Exercise Test (CPET) - RER
Hide Description The Respiratory Exchange Ratio (VCO2/VO2) was determined during a cardiopulmonary exercise test (CPET). VCO2/VO2 is calculated by measuring the volume of carbon dioxide and oxygen the participant breathes during CPET. When the volume of carbon dioxide exceeds that of oxygen, it reflects a change from aerobic metabolism to anaerobic metabolism. When a participant has a Respiratory Exchange Ratio (RER) during CPET that is equal or greater than 1.1 it is considered a sufficient exercise effort. Results compared Healthy Volunteer Participants to ME/CFS Participants.
Time Frame At time of AT during CPET
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Healthy Volunteer Participants ME/CFS Participants
Hide Arm/Group Description:
Participants found to be healthy after a medical and psychiatric evaluation who completed the Cardiopulmonary Exercise Test (CPET).
Participants with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: Ratio
1.3011  (0.0791) 1.2415  (0.1156)
3.Other Pre-specified Outcome
Title Characterization of Total Body Energy Use (Bioenergetics/Metabolic)
Hide Description The total amount of energy expended per unit of time as measured by whole-room indirect calorimetry. This method measures the amount of oxygen consumed and carbon dioxide produced which can be used to calculate the amount of energy produced by biological oxidation and is measured by kilocalories per day. Measures were taken from Healthy and ME/CFS participants.
Time Frame 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Procedure added to Phenotyping Phase after enrollment started.
Arm/Group Title Healthy Volunteer Participants ME/CFS Participants
Hide Arm/Group Description:
Participants found to be healthy after a medical and psychiatric evaluation.
Participants with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Overall Number of Participants Analyzed 11 16
Mean (Standard Deviation)
Unit of Measure: kcal/day
1858.9  (353.3) 1862.1  (390.5)
4.Other Pre-specified Outcome
Title Characterization of the Immune System and Inflammation - WBC
Hide Description Blood and CSF were collected from healthy and ME/CFS participants at baseline. A comparison of the White Blood Cell (WBC) Count, i.e., a measurement of the number of white blood cells in the blood, in the two populations is reported. Low values can suggest immune deficiencies. High values can suggest infection or inflammation.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Healthy Volunteer Participants ME/CFS Participants
Hide Arm/Group Description:
Participants found to be healthy after a medical and psychiatric evaluation.
Participants with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Overall Number of Participants Analyzed 21 17
Mean (Standard Deviation)
Unit of Measure: number of WBCs(K)/uL
5.907  (1.536) 6.143  (1.243)
5.Other Pre-specified Outcome
Title Characterization of the Immune System and Inflammation - ESR
Hide Description Blood and CSF were collected from healthy and ME/CFS participants at baseline. A comparison of the results of the Erythrocyte Sedimentation Rate (ESR), i.e., a measure of how quickly red blood cells settle at the bottom of a test tube, in the two populations is reported. A faster than normal rate of settling suggests inflammation.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Healthy Volunteer Participants ME/CFS Participants
Hide Arm/Group Description:
Participants found to be healthy after a medical and psychiatric evaluation.
Participants with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Overall Number of Participants Analyzed 21 17
Mean (Standard Deviation)
Unit of Measure: mm/hr
7.43  (6.13) 10.1  (11.9)
6.Other Pre-specified Outcome
Title Characterization of the Immune System and Inflammation - CRP
Hide Description Blood and CSF were collected from healthy and ME/CFS participants at baseline. A comparison of the results of C-Reactive Protein (CRP), i.e., a measurement of a protein that is made by the liver, in the two populations is reported. A higher level than normal suggests inflammation.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Healthy Volunteer Participants ME/CFS Participants
Hide Arm/Group Description:
Participants found to be healthy after a medical and psychiatric evaluation.
Participants with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Overall Number of Participants Analyzed 21 17
Mean (Standard Deviation)
Unit of Measure: mg/L
3.29  (6.85) 1.4  (2.22)
7.Other Pre-specified Outcome
Title Characterization of the Immune System and Inflammation - WBC in CFS
Hide Description Blood and CSF were collected from healthy and ME/CFS participants at baseline. A comparison of the White Blood cell Count in Cerebrospinal Fluid (WBC in CFS), i.e., a measurement of the number of white blood cells in the cerebrospinal fluid, in the two populations is reported. Higher levels than normal suggest inflammation or infection in the central nervous system.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Healthy Volunteer Participants ME/CFS Participants
Hide Arm/Group Description:
Participants found to be healthy after a medical and psychiatric evaluation.
Participants with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Overall Number of Participants Analyzed 21 17
Mean (Standard Deviation)
Unit of Measure: number WBCs/uL
1.0  (1.124) 1.313  (1.662)
8.Other Pre-specified Outcome
Title Mitochondrial Extracellular Flux Assay
Hide Description The oxygen consumption rate of peripheral blood mononuclear cells per unit of time when the cells are in their normal, unprovoked state of function measured in Basal (units) was measured in Healthy and ME/CFS participants at baseline. This is a standard measure of mitochondrial respiration that is responsible for providing energy to cells.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Technical issues with assay prevented complete dataset.
Arm/Group Title Healthy Volunteer Participants ME/CFS Participants
Hide Arm/Group Description:
Participants found to be healthy after a medical and psychiatric evaluation.
Participants with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Overall Number of Participants Analyzed 13 14
Median (Inter-Quartile Range)
Unit of Measure: Pmol/min
46.7
(26.2 to 58.0)
52.1
(41.0 to 84.9)
9.Other Pre-specified Outcome
Title Effect of Maximal Exertion on Autonomic Function as Measured by SDNNi in Healthy and ME/CFS Participants.
Hide Description Variability of the time between heartbeats can be used to measure alterations in autonomic function. The Standard Deviation of the Normal-to-Normal Intervals (SDNNi) is a measure of the amount of beat to beat variability between each normal heartbeat collected over a 24 hour period. These results compare the SDNNi in healthy and ME/CFS participants at baseline.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Data from participants on cardiac medications were excluded.
Arm/Group Title Healthy Volunteer Participants ME/CFS Participants
Hide Arm/Group Description:
Participants found to be healthy after a medical and psychiatric evaluation.
Participants with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Overall Number of Participants Analyzed 19 13
Mean (Inter-Quartile Range)
Unit of Measure: ms
67.8
(58.9 to 77.1)
56.3
(46.1 to 64.4)
10.Other Pre-specified Outcome
Title Clinical Response Effect of Tilt Table Testing
Hide Description Persons with autonomic dysfunction will often have symptoms provoked by having an up-to-40 minutes long tilt table test. The percentage of participants in each group having severe enough symptoms which required the test to be stopped in Healthy and ME/CFS participants at baseline.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Two participants were unable to complete due to technical difficulties with procedure.
Arm/Group Title Healthy Volunteer Participants ME/CFS Participants
Hide Arm/Group Description:
Participants found to be healthy after a medical and psychiatric evaluation.
Participants with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Overall Number of Participants Analyzed 19 17
Measure Type: Number
Unit of Measure: percentage of participants
36.8 58.8
11.Other Pre-specified Outcome
Title Characterization of the Pattern of Microbiome in Stool
Hide Description Stool samples were taken from Healthy and ME/CFS participants at baseline. The number of specific types of bacteria, using the Least Known Taxon (LTK) units, were measured with the Shotgun Metagenomic method.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Single batch analyzed on subset of participants
Arm/Group Title Healthy Volunteer Participants ME/CFS Participants
Hide Arm/Group Description:
Participants found to be healthy after a medical and psychiatric evaluation.
Participants with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Overall Number of Participants Analyzed 17 15
Mean (Standard Deviation)
Unit of Measure: LTK
477  (32.9) 427  (44.1)
12.Other Pre-specified Outcome
Title Test of Variables of Attention (TOVA)
Hide Description The TOVA is a measure of cognitive function that assesses attention and inhibitory control. The test is used to measure a number of variables involving the test taker's response to either a visual or auditory stimulus measured during a "simple, yet boring, computer game". These measurements are then compared to the measurements of a group of people without attention disorders who took the T.O.V.A. The range of values for the score, after normalization to the population, is -10 to +10, with a lower score representing a worse attention score. The test was administered to Healthy and ME/CFS participants at baseline.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Not all participants were able to complete test.
Arm/Group Title Healthy Volunteer Participants ME/CFS Participants
Hide Arm/Group Description:
Participants found to be healthy after a medical and psychiatric evaluation.
Participants with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Overall Number of Participants Analyzed 18 15
Mean (Standard Deviation)
Unit of Measure: score on a scale
1.1  (3.6) 0.9  (4.7)
13.Other Pre-specified Outcome
Title Paced Auditory Serial Addition Test (PASAT)
Hide Description The PASAT is a measure of cognitive function that assesses auditory information processing speed and flexibility, as well as calculation ability. Single digits are presented every 3 seconds and the patient must add each new digit to the one immediately prior to it. The test score is the total number of correct trials out of a possible 60. The test was administered to Healthy and ME/CFS participants at baseline.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Not all participants were able to complete test.
Arm/Group Title Healthy Volunteer Participants ME/CFS Participants
Hide Arm/Group Description:
Participants found to be healthy after a medical and psychiatric evaluation.
Participants with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Overall Number of Participants Analyzed 17 15
Mean (Standard Deviation)
Unit of Measure: score on a scale
52.4  (12.1) 52  (11)
Time Frame Up to 2 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Healthy Volunteer Participants ME/CFS Participants
Hide Arm/Group Description Participants found to be healthy after a medical and psychiatric evaluation. Participants with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
All-Cause Mortality
Healthy Volunteer Participants ME/CFS Participants
Affected / at Risk (%) Affected / at Risk (%)
Total   0/25 (0.00%)      0/27 (0.00%)    
Hide Serious Adverse Events
Healthy Volunteer Participants ME/CFS Participants
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/25 (0.00%)      0/27 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Healthy Volunteer Participants ME/CFS Participants
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/25 (56.00%)      23/27 (85.19%)    
Gastrointestinal disorders     
Abdominal pain *  1/25 (4.00%)  1 1/27 (3.70%)  1
Lip pain *  0/25 (0.00%)  0 1/27 (3.70%)  1
Vomiting *  0/25 (0.00%)  0 1/27 (3.70%)  1
Nausea *  1/25 (4.00%)  1 0/27 (0.00%)  0
General disorders     
Fatigue *  1/25 (4.00%)  1 6/27 (22.22%)  12
Localized edema *  0/25 (0.00%)  0 1/27 (3.70%)  1
Immune system disorders     
Allergic reaction *  0/25 (0.00%)  0 1/27 (3.70%)  1
Injury, poisoning and procedural complications     
Bruising *  0/25 (0.00%)  0 1/27 (3.70%)  1
Musculoskeletal and connective tissue disorders     
Arthalgia *  1/25 (4.00%)  1 1/27 (3.70%)  1
Back pain *  7/25 (28.00%)  9 12/27 (44.44%)  13
Generalized muscle weakness *  0/25 (0.00%)  0 1/27 (3.70%)  1
Neck pain *  0/25 (0.00%)  0 1/27 (3.70%)  1
Extremity pain *  2/25 (8.00%)  2 3/27 (11.11%)  3
Myaligia *  1/25 (4.00%)  1 0/27 (0.00%)  0
Nervous system disorders     
Aphonia *  0/25 (0.00%)  0 1/27 (3.70%)  1
Cerebrospinal fluid leakage *  6/25 (24.00%)  6 3/27 (11.11%)  3
Dizziness *  4/25 (16.00%)  4 4/27 (14.81%)  4
Headache *  3/25 (12.00%)  3 11/27 (40.74%)  15
Movements Involuntary *  0/25 (0.00%)  0 1/27 (3.70%)  1
Paresthesia *  2/25 (8.00%)  3 4/27 (14.81%)  4
Pre-syncope *  0/25 (0.00%)  0 1/27 (3.70%)  1
Psychiatric disorders     
Insomnia *  0/25 (0.00%)  0 1/27 (3.70%)  1
Respiratory, thoracic and mediastinal disorders     
Dyspnea *  1/25 (4.00%)  1 1/27 (3.70%)  1
Vascular disorders     
Hypotension *  3/25 (12.00%)  3 2/27 (7.41%)  2
*
Indicates events were collected by non-systematic assessment
[Not Specified]
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Brian Walitt
Organization: National Institutes of Health
Phone: 202-549-7669
EMail: brian.walitt@nih.gov
Layout table for additonal information
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier: NCT02669212    
Other Study ID Numbers: 160058
16-N-0058
First Submitted: January 29, 2016
First Posted: February 1, 2016
Results First Submitted: January 9, 2023
Results First Posted: April 18, 2023
Last Update Posted: April 18, 2023