Myalgic Encephalomyelitis Chronic Fatigue at the National Institutes of Health
Condition: Chronic Fatigue Syndrome
MeSH terms: Encephalomyelitis; Fatigue Syndrome, Chronic; Syndrome; Fatigue
Study type: Interventional

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
    

Intervention name(s): Cardiopulmonary Exercise Test (CPET)
Intervention type(s): Behavioral
Intervention description(s): All participants will undergo an exercise stress test
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Screening
Keywords: Chronic Fatigue Syndrome; Lyme Disease; Healthy Volunteers; Movement Disorder