Myalgic Encephalomyelitis Chronic Fatigue at the National Institutes of Health

Not Applicable

Completed

Conditions: Chronic Fatigue Syndrome

Interventions: Behavioral: Cardiopulmonary Exercise Test (CPET)

Registration Number: NCT02669212

Lead Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)

Brief Summary: Background:

Post-Infectious Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (PI-ME/CFS) refers to long-lasting and disabling fatigue or malaise, inability to recover after exercise, and physical and emotional discomfort that may occur after a person has an infection. Researchers want to learn more about its causes.

Objective:

To learn more about PI-ME/CFS.

Eligibility:

Adults ages 18-60 years who have finished at least 7th grade education and either:

have ME/CFS that started after an infection

OR had Lyme disease, were treated, and returned to normal health

OR are healthy volunteers

Design:

Participants will initially have a 2-5 day inpatient visit at the National Institutes of Health Clinical Center in Bethesda. During the visit, participants will have:

Medical history

Physical exam

Intravenous (IV) line. A thin plastic tube is inserted into a vein.

Blood and urine collected

Magnetic resonance imaging (MRI). Participants will lie in a machine that takes pictures of their brain. They may get a dye through their IV.

Grip strength tested

Saliva, cheek swab, and stool collected

Tilt table test with measures of body functions such as sweating and breathing, blood pressure, and heart rate and blood and urine sample collection

Collection of blood cells. Participants can choose to have the blood drawn through the IV or through a machine that filters blood cells and returns the liquid blood back into the participant s vein.

Lumbar puncture. Fluid will be removed by placement of a needle between the back bones.

Heart monitoring

Sleep study for participants with PI ME/CFS

Questions about the participant s life and how they are feeling

Questions from a neuropsychologist

Questions from an occupational therapist for participants with PI ME/CFS

Questinos from a nutritionist

After the initial visit participants will return home. Participants evaluated for PI-ME/CFS during the first visit will have their information reviewed by an adjudication panel of experts in the diagnosis and care of ME/CFS to determine if they are eligible to participate in the second study visit.

Eligible participants will be invited back for a second study visit. If a participant was taking certain medications during the first visit, they may be asked to taper off of them prior to the second visit and report any problems. They will also receive an activity monitor, fatigue diary, and nutrition log to use for at least one week prior to their second visit.

Participants who are eligible will return for a 5-10 day inpatient hospital visit at the National Institutes of Health Clinical Center. During the visit, participants will undergo measurements before and up to 96 hours after performing a stationary bike exercise test. The purpose of the exercise test is to provoke ME/CFS symptoms (post-exertional malaise). Tests will be performed before and after exercise testing. These include:

Sleeping in a room that measures how the body uses energy with EEG monitoring

Eating a controlled diet

Performing vigorous exercise for 10-15 minutes

Questions about how participants are feeling

Questions about what participants usually eat

Samples of saliva, blood, urine and stool

Wearing an activity monitor

Having an Xray that measures body composition

Thinking and memory tests

Heart monitoring

Transcranial magnetic stimulation. A brief electrical current to the scalp creates a magnetic pulse that affects brain activity.

Magnetic resonance imaging (MRI). Participants will lie in a machine that takes pictures of their brain. They will do thinking and exercise tasks during the MRI.

Lumbar puncture. Fluid will be removed by placement of a needle between the back bones.

Detailed Description: Objective:

The primary objective is to explore the clinical and biological phenotypes of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS). The secondary objective is to explore the pathophysiology of fatigue and post-exertional malaise (PEM).

Study population:

Up to 206 persons will be enrolled as part of this protocol. Up to 150 persons aged 18-60 will be part of 3 study groups: 50 ME/CFS patients whose fatigue began after an infection, 50 non-fatigued participants with a documented history of a full recovery from COVID-19 infection, and 50 healthy volunteers. The study has a target of completing all study procedures on 20 enrolled participants in each group. Up to an additional 36 persons reporting a community diagnosis of ME/CFS will be enrolled into focus groups to discuss the experience of post-exertional malaise. Up to an additional 10 healthy volunteers and 10 ME/CFS patients may be enrolled to refine the protocol's electrophysiological and neuroimaging techniques.

Design:

This is a single-center, exploratory, cross-sectional study of PI-ME/CFS. Participants will have a phenotyping visit, which will encompass a 2-5 day long inpatient admission at the NIH Clinical Center. Case status for ME/CFS participants will be determined after the phenotyping visit by a case adjudication process utilizing an expert physician committee and published guidelines. Adjudicated participants meeting inclusion criteria will be invited back to participate in an exercise stress visit, which will encompass a 5-10 day long inpatient admission. Detailed subjective and objective measurements and biological specimens will be serially collected before and up to 96 hours after a peak exercise test capable of inducing post-exertional malaise during this visit. All procedures will be completed on all three study groups to allow for optimal inter-group comparisons.

Outcome measures:

The primary purpose of this protocol is to perform exploratory analysis of collected samples for the generation of new hypotheses regarding ME/CFS. The types of analyses to be performed will be wide ranging. Planned areas of focus include:

1. Characterization of the immune system and inflammation at baseline

2. Characterization of the pattern of microbiome in collected samples at baseline

3. Characterization of bioenergetics, autonomic, and metabolic function in collected samples at baseline

4. Characterization of neurocognition at baseline

5. Characterization of autonomic function at baseline

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 52

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Healthy Volunteer Participants	Cardiopulmonary Exercise Test (CPET)	Healthy volunteer participants
ME/CFS Participants	Cardiopulmonary Exercise Test (CPET)	Participants with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Primary Outcome Measures

Name	Time	Method
Cardiopulmonary Exercise Test (CPET) - RER	At time of AT during CPET	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.
Cardiopulmonary Exercise Test (CPET) - ATVO2rel	At time of AT during CPET	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.

Secondary Outcome Measures