Trial Outcomes & Findings for Myalgic Encephalomyelitis Chronic Fatigue at the National Institutes of Health (NCT NCT02669212)
NCT ID: NCT02669212
Last Updated: 2023-04-18
Results Overview
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.
COMPLETED
NA
52 participants
At time of AT during CPET
2023-04-18
Participant Flow
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.
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.
Participant milestones
| Measure |
Healthy Volunteer Participants
Participants found to be healthy after a medical and psychiatric evaluation.
|
ME/CFS Participants
Participants with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
|
|---|---|---|
|
Overall Study
STARTED
|
25
|
27
|
|
Overall Study
COMPLETED
|
21
|
17
|
|
Overall Study
NOT COMPLETED
|
4
|
10
|
Reasons for withdrawal
| Measure |
Healthy Volunteer Participants
Participants found to be healthy after a medical and psychiatric evaluation.
|
ME/CFS Participants
Participants with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Medical Condition
|
3
|
4
|
|
Overall Study
Withdrawal by Subject
|
0
|
2
|
|
Overall Study
Excluded - determined NOT post-infectious
|
0
|
4
|
Baseline Characteristics
Myalgic Encephalomyelitis Chronic Fatigue at the National Institutes of Health
Baseline characteristics by cohort
| Measure |
Healthy Volunteer Participants
n=25 Participants
Participants found to be healthy after a medical and psychiatric evaluation.
|
ME/CFS Participants
n=27 Participants
Participants with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
|
Total
n=52 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
25 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
42.24 Years
STANDARD_DEVIATION 13.46 • n=5 Participants
|
37.82 Years
STANDARD_DEVIATION 14.72 • n=7 Participants
|
40.35 Years
STANDARD_DEVIATION 13.48 • n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
23 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
21 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At time of AT during CPETPopulation: COVID-19 pandemic halted return visit for participation in Exercise Phase of trial.
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.
Outcome measures
| Measure |
Healthy Volunteers
n=9 Participants
Participants found to be healthy after a medical and psychiatric evaluation who completed the Cardiopulmonary Exercise Test (CPET).
|
ME/CFS Participants
n=9 Participants
ME/CFS Participants who complete the Cardiopulmonary Exercise Test (CPET)
|
|---|---|---|
|
Cardiopulmonary Exercise Test (CPET) - ATVO2rel
|
16.0 mL/kg/min
Standard Deviation 4.3
|
10.6 mL/kg/min
Standard Deviation 3.8
|
PRIMARY outcome
Timeframe: At time of AT during CPETThe 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.
Outcome measures
| Measure |
Healthy Volunteers
n=9 Participants
Participants found to be healthy after a medical and psychiatric evaluation who completed the Cardiopulmonary Exercise Test (CPET).
|
ME/CFS Participants
n=9 Participants
ME/CFS Participants who complete the Cardiopulmonary Exercise Test (CPET)
|
|---|---|---|
|
Cardiopulmonary Exercise Test (CPET) - RER
|
1.3011 Ratio
Standard Deviation 0.0791
|
1.2415 Ratio
Standard Deviation 0.1156
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 hoursPopulation: Procedure added to Phenotyping Phase after enrollment started.
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.
Outcome measures
| Measure |
Healthy Volunteers
n=11 Participants
Participants found to be healthy after a medical and psychiatric evaluation who completed the Cardiopulmonary Exercise Test (CPET).
|
ME/CFS Participants
n=16 Participants
ME/CFS Participants who complete the Cardiopulmonary Exercise Test (CPET)
|
|---|---|---|
|
Characterization of Total Body Energy Use (Bioenergetics/Metabolic)
|
1858.9 kcal/day
Standard Deviation 353.3
|
1862.1 kcal/day
Standard Deviation 390.5
|
OTHER_PRE_SPECIFIED outcome
Timeframe: BaselineBlood 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.
Outcome measures
| Measure |
Healthy Volunteers
n=21 Participants
Participants found to be healthy after a medical and psychiatric evaluation who completed the Cardiopulmonary Exercise Test (CPET).
|
ME/CFS Participants
n=17 Participants
ME/CFS Participants who complete the Cardiopulmonary Exercise Test (CPET)
|
|---|---|---|
|
Characterization of the Immune System and Inflammation - WBC
|
5.907 number of WBCs(K)/uL
Standard Deviation 1.536
|
6.143 number of WBCs(K)/uL
Standard Deviation 1.243
|
OTHER_PRE_SPECIFIED outcome
Timeframe: BaselineBlood 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.
Outcome measures
| Measure |
Healthy Volunteers
n=21 Participants
Participants found to be healthy after a medical and psychiatric evaluation who completed the Cardiopulmonary Exercise Test (CPET).
|
ME/CFS Participants
n=17 Participants
ME/CFS Participants who complete the Cardiopulmonary Exercise Test (CPET)
|
|---|---|---|
|
Characterization of the Immune System and Inflammation - ESR
|
7.43 mm/hr
Standard Deviation 6.13
|
10.1 mm/hr
Standard Deviation 11.9
|
OTHER_PRE_SPECIFIED outcome
Timeframe: BaselineBlood 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.
Outcome measures
| Measure |
Healthy Volunteers
n=21 Participants
Participants found to be healthy after a medical and psychiatric evaluation who completed the Cardiopulmonary Exercise Test (CPET).
|
ME/CFS Participants
n=17 Participants
ME/CFS Participants who complete the Cardiopulmonary Exercise Test (CPET)
|
|---|---|---|
|
Characterization of the Immune System and Inflammation - CRP
|
3.29 mg/L
Standard Deviation 6.85
|
1.4 mg/L
Standard Deviation 2.22
|
OTHER_PRE_SPECIFIED outcome
Timeframe: BaselineBlood 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.
Outcome measures
| Measure |
Healthy Volunteers
n=21 Participants
Participants found to be healthy after a medical and psychiatric evaluation who completed the Cardiopulmonary Exercise Test (CPET).
|
ME/CFS Participants
n=17 Participants
ME/CFS Participants who complete the Cardiopulmonary Exercise Test (CPET)
|
|---|---|---|
|
Characterization of the Immune System and Inflammation - WBC in CFS
|
1.0 number WBCs/uL
Standard Deviation 1.124
|
1.313 number WBCs/uL
Standard Deviation 1.662
|
OTHER_PRE_SPECIFIED outcome
Timeframe: BaselinePopulation: Technical issues with assay prevented complete dataset.
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.
Outcome measures
| Measure |
Healthy Volunteers
n=13 Participants
Participants found to be healthy after a medical and psychiatric evaluation who completed the Cardiopulmonary Exercise Test (CPET).
|
ME/CFS Participants
n=14 Participants
ME/CFS Participants who complete the Cardiopulmonary Exercise Test (CPET)
|
|---|---|---|
|
Mitochondrial Extracellular Flux Assay
|
46.7 Pmol/min
Interval 26.2 to 58.0
|
52.1 Pmol/min
Interval 41.0 to 84.9
|
OTHER_PRE_SPECIFIED outcome
Timeframe: BaselinePopulation: Data from participants on cardiac medications were excluded.
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.
Outcome measures
| Measure |
Healthy Volunteers
n=19 Participants
Participants found to be healthy after a medical and psychiatric evaluation who completed the Cardiopulmonary Exercise Test (CPET).
|
ME/CFS Participants
n=13 Participants
ME/CFS Participants who complete the Cardiopulmonary Exercise Test (CPET)
|
|---|---|---|
|
Effect of Maximal Exertion on Autonomic Function as Measured by SDNNi in Healthy and ME/CFS Participants.
|
67.8 ms
Interval 58.9 to 77.1
|
56.3 ms
Interval 46.1 to 64.4
|
OTHER_PRE_SPECIFIED outcome
Timeframe: BaselinePopulation: Two participants were unable to complete due to technical difficulties with procedure.
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.
Outcome measures
| Measure |
Healthy Volunteers
n=19 Participants
Participants found to be healthy after a medical and psychiatric evaluation who completed the Cardiopulmonary Exercise Test (CPET).
|
ME/CFS Participants
n=17 Participants
ME/CFS Participants who complete the Cardiopulmonary Exercise Test (CPET)
|
|---|---|---|
|
Clinical Response Effect of Tilt Table Testing
|
36.8 percentage of participants
|
58.8 percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: BaselinePopulation: Single batch analyzed on subset of participants
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.
Outcome measures
| Measure |
Healthy Volunteers
n=17 Participants
Participants found to be healthy after a medical and psychiatric evaluation who completed the Cardiopulmonary Exercise Test (CPET).
|
ME/CFS Participants
n=15 Participants
ME/CFS Participants who complete the Cardiopulmonary Exercise Test (CPET)
|
|---|---|---|
|
Characterization of the Pattern of Microbiome in Stool
|
477 LTK
Standard Deviation 32.9
|
427 LTK
Standard Deviation 44.1
|
OTHER_PRE_SPECIFIED outcome
Timeframe: BaselinePopulation: Not all participants were able to complete test.
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.
Outcome measures
| Measure |
Healthy Volunteers
n=18 Participants
Participants found to be healthy after a medical and psychiatric evaluation who completed the Cardiopulmonary Exercise Test (CPET).
|
ME/CFS Participants
n=15 Participants
ME/CFS Participants who complete the Cardiopulmonary Exercise Test (CPET)
|
|---|---|---|
|
Test of Variables of Attention (TOVA)
|
1.1 score on a scale
Standard Deviation 3.6
|
0.9 score on a scale
Standard Deviation 4.7
|
OTHER_PRE_SPECIFIED outcome
Timeframe: BaselinePopulation: Not all participants were able to complete test.
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.
Outcome measures
| Measure |
Healthy Volunteers
n=17 Participants
Participants found to be healthy after a medical and psychiatric evaluation who completed the Cardiopulmonary Exercise Test (CPET).
|
ME/CFS Participants
n=15 Participants
ME/CFS Participants who complete the Cardiopulmonary Exercise Test (CPET)
|
|---|---|---|
|
Paced Auditory Serial Addition Test (PASAT)
|
52.4 score on a scale
Standard Deviation 12.1
|
52 score on a scale
Standard Deviation 11
|
Adverse Events
Healthy Volunteer Participants
ME/CFS Participants
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Healthy Volunteer Participants
n=25 participants at risk
Participants found to be healthy after a medical and psychiatric evaluation.
|
ME/CFS Participants
n=27 participants at risk
Participants with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
4.0%
1/25 • Number of events 1 • Up to 2 weeks
|
3.7%
1/27 • Number of events 1 • Up to 2 weeks
|
|
Immune system disorders
Allergic reaction
|
0.00%
0/25 • Up to 2 weeks
|
3.7%
1/27 • Number of events 1 • Up to 2 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthalgia
|
4.0%
1/25 • Number of events 1 • Up to 2 weeks
|
3.7%
1/27 • Number of events 1 • Up to 2 weeks
|
|
Nervous system disorders
Aphonia
|
0.00%
0/25 • Up to 2 weeks
|
3.7%
1/27 • Number of events 1 • Up to 2 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
28.0%
7/25 • Number of events 9 • Up to 2 weeks
|
44.4%
12/27 • Number of events 13 • Up to 2 weeks
|
|
Nervous system disorders
Cerebrospinal fluid leakage
|
24.0%
6/25 • Number of events 6 • Up to 2 weeks
|
11.1%
3/27 • Number of events 3 • Up to 2 weeks
|
|
Injury, poisoning and procedural complications
Bruising
|
0.00%
0/25 • Up to 2 weeks
|
3.7%
1/27 • Number of events 1 • Up to 2 weeks
|
|
Nervous system disorders
Dizziness
|
16.0%
4/25 • Number of events 4 • Up to 2 weeks
|
14.8%
4/27 • Number of events 4 • Up to 2 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
4.0%
1/25 • Number of events 1 • Up to 2 weeks
|
3.7%
1/27 • Number of events 1 • Up to 2 weeks
|
|
General disorders
Fatigue
|
4.0%
1/25 • Number of events 1 • Up to 2 weeks
|
22.2%
6/27 • Number of events 12 • Up to 2 weeks
|
|
Nervous system disorders
Headache
|
12.0%
3/25 • Number of events 3 • Up to 2 weeks
|
40.7%
11/27 • Number of events 15 • Up to 2 weeks
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
0.00%
0/25 • Up to 2 weeks
|
3.7%
1/27 • Number of events 1 • Up to 2 weeks
|
|
Vascular disorders
Hypotension
|
12.0%
3/25 • Number of events 3 • Up to 2 weeks
|
7.4%
2/27 • Number of events 2 • Up to 2 weeks
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/25 • Up to 2 weeks
|
3.7%
1/27 • Number of events 1 • Up to 2 weeks
|
|
Gastrointestinal disorders
Lip pain
|
0.00%
0/25 • Up to 2 weeks
|
3.7%
1/27 • Number of events 1 • Up to 2 weeks
|
|
General disorders
Localized edema
|
0.00%
0/25 • Up to 2 weeks
|
3.7%
1/27 • Number of events 1 • Up to 2 weeks
|
|
Nervous system disorders
Movements Involuntary
|
0.00%
0/25 • Up to 2 weeks
|
3.7%
1/27 • Number of events 1 • Up to 2 weeks
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/25 • Up to 2 weeks
|
3.7%
1/27 • Number of events 1 • Up to 2 weeks
|
|
Musculoskeletal and connective tissue disorders
Extremity pain
|
8.0%
2/25 • Number of events 2 • Up to 2 weeks
|
11.1%
3/27 • Number of events 3 • Up to 2 weeks
|
|
Nervous system disorders
Paresthesia
|
8.0%
2/25 • Number of events 3 • Up to 2 weeks
|
14.8%
4/27 • Number of events 4 • Up to 2 weeks
|
|
Nervous system disorders
Pre-syncope
|
0.00%
0/25 • Up to 2 weeks
|
3.7%
1/27 • Number of events 1 • Up to 2 weeks
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/25 • Up to 2 weeks
|
3.7%
1/27 • Number of events 1 • Up to 2 weeks
|
|
Gastrointestinal disorders
Nausea
|
4.0%
1/25 • Number of events 1 • Up to 2 weeks
|
0.00%
0/27 • Up to 2 weeks
|
|
Musculoskeletal and connective tissue disorders
Myaligia
|
4.0%
1/25 • Number of events 1 • Up to 2 weeks
|
0.00%
0/27 • Up to 2 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place