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Myalgic Encephalomyelitis Chronic Fatigue at the National Institutes of Health

This study is currently recruiting participants.
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Verified September 6, 2017 by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier:
NCT02669212
First received: January 29, 2016
Last updated: September 12, 2017
Last verified: September 6, 2017
  Purpose

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.


Condition
Chronic Fatigue Syndrome

Study Type: Observational
Study Design: Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):

Primary Outcome Measures:
  • To explore the clinical and biological phenotypes of post-infectious chronic fatigue syndrome (PI-ME/CFS) [ Time Frame: Week 1: Single time point measurement ]

Secondary Outcome Measures:
  • To explore the pathophysiologies of fatigue and post-exertional malaise (PEM). [ Time Frame: Week 2: Pre-exercise stress, 4 hours, 24 hours, and 48 hours. Additional measurement for PI-ME/CFS at 72 and 96 hrs. ]
    Fatigue will be explored using tasks designed to create muscular and cognitive fatigue. PEM will be explored using an exercise stress and measuring the symptomatic and biological alterations that occur before and afterwards.


Estimated Enrollment: 206
Study Start Date: January 20, 2016
Estimated Study Completion Date: September 15, 2020
Estimated Primary Completion Date: September 15, 2018 (Final data collection date for primary outcome measure)
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 Lyme disease exposure and treatment, 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:

  1. Characterization of the immune system and inflammatory signaling in blood and cerebrospinal fluid (CSF)
  2. Characterization of the pattern of microbiome in gut, blood and CSF
  3. Characterization of physical and cognitive fatigue using functional magnetic resonance imaging and transcranial magnetic stimulation
  4. Effect of maximal exertion on neurocognition
  5. Effect of maximal exertion on brain function and connectivity
  6. Effect of maximal exertion on markers of immune dysfunction and inflammation
  7. Effect of maximal exertion on metabolic function
  8. Effect of maximal exertion on autonomic function
  9. Effect of maximal exertion on gene expression profiles in blood and CSF
  Eligibility

Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:
  • Inclusion criteria for all participants

    1. Adult participants aged 18-60 years at the time of enrollment.
    2. Self-reported completion of at least the 7th grade of school.
    3. Ability to speak, read, and understand English.
    4. Willing and able to complete all study procedures
    5. Participant has a primary care physician at the time of enrollment.
    6. Able to provide informed consent.
  • Additional inclusion criteria for participants with PI-ME/CFS for the phenotyping visit

    1. A self-reported illness narrative of the development of persistent fatigue and post-exertional malaise as the consequence of an acute infection. The persistent fatigue may have an acute onset or become progressively worse over 6 months.
    2. Licensed Independent Practitioner documentation of ME/CFS onset:

      • Medical documentation of absence of symptoms within one year of ME/CFS onset.
      • Documentation of a medical evaluation for symptoms of an acute infection or documentation of a medical evaluation of persistent symptoms within 2 months following an assumed infection.
    3. Persistent fatigue and PEM onset less than 5 years prior to enrollment.
  • Additional inclusion criteria for participants with PI-ME/CFS for the exercise stress visit

    1. Be unanimously considered to be a case of PI-ME/CFS by the protocol s adjudication committee.
    2. Meet the 1994 Fukuda Criteria and the 2003 Canadian Consensus Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
    3. Have moderate to severe clinical symptom severity:

      • Severe fatigue as determined using the Multidimensional Fatigue Inventory (MFI): score of greater than or equal to 13 on the general fatigue subscale or greater than or equal to 10 on the reduced activity subscale.
      • Functional impairment as determined using the Short-Form 36 (SF-36): score of less than or equal to 70 physical function subscale, or less than or equal to 50 on role physical subscale, or less than or equal to 75 on social function subscale
  • Additional inclusion criteria for healthy volunteer group
  • Additional inclusion criteria for Documented Lyme Infection - Asymptomatic group

    1. Medical record documentation of fulfilling the probable or confirmed 2011 CDC Lyme Disease National Surveillance Case Definitions (http://wwwn.cdc.gov/nndss/conditions/lyme-disease/case-definition/2011/):

      1. Probable: A case of physician-diagnosed Lyme disease that meets laboratory criteria of evidence of infection (positive culture for B.burgdoferi, or two-tiered testing using criteria, or single-tier IgG immunoblot seropositivity using criteria, or CSF antibody positive for B.burgdoferi by Enzyme Immunoassay or Immunofluorescence Assay, when the titer is higher than it was in serum.
      2. Confirmed: A case of erythema migrans with a known exposure, or a case of erythema migrans with laboratory evidence of infection and without a known exposure, or a case with at least one late manifestation that has laboratory evidence of infection.
    2. Have received accepted antibiotic treatment for Lyme Disease greater than or equal to 6 months prior to enrollment but less than 5 years prior to enrollment documented in their medical records.

      EXCLUSION CRITERIA:

  • Exclusion criteria for all participants

    1. Current or past psychotic disorder including depression with psychosis, bipolar disorder, and schizophrenia
    2. Current DSM-5-defined major depression disorder, generalized anxiety disorder, post-traumatic stress disorder, panic disorder, or obsessive-compulsive disorder unless managed for more than six months with a stable treatment regimen
    3. Current or prior substance use disorder as diagnosed on the Structured Clinical Interview for DSM-5 (SCID-5) or positive urine toxicology results at enrollment
    4. Current suicidal ideation
    5. History of head injury with loss of consciousness or amnesia lasting greater than a few seconds within lasta five years or lasting greater than 5 minutes at any point during their lifetime.
    6. Women who are pregnant, actively seeking to become pregnant, or have been pregnant in the year prior to study enrollment.
    7. Current or previous malignancy. Certain dermatologic malignancies (e.g. basal cell carcinoma) will be allowed. A history of malignancy that have fully resolved with surgical resection only (i.e. no chemotherapy, radiation therapy, or immunotherapy) will be allowed.
    8. Current immunologic disorder (e.g. Type 1 diabetes, rheumatoid arthritis)
    9. Current or previous long term immune suppressive or immunomodulatory therapy. Systemic steroid use, even short-term, must not have been used within the month prior to enrollment
    10. Any medical condition (eg, congestive heart failure, coronary artery disease, chronic obstructive pulmonary disease, severe osteoarthritis, poorly controlled asthma) that would make the study procedures risky for the participant (e.g. exercise-induced angina and asthma) or that may confound the study results (e.g. untreated obstructive sleep apnea, severe osteoarthritis).
    11. Participation in a clinical protocol (e.g. anti-inflammatory drug intervention study) which includes an intervention that may affect the results of the current study.
    12. Inability to perform the bicycling exercise task.
    13. Clinically significant claustrophobia
    14. Not willing to allow for research samples to be shared with other researchers.
    15. Employees or staff at NIH that are directly supervised by the primary investigator or associate investigators.
  • Additional exclusion criteria for participants with PI-ME/CFS for phenotyping visit

    1. Significant neurological disorder (e.g. neurodegenerative disorder, stroke, epilepsy).
    2. PI-ME/CFS disease severity that makes it impossible for the volunteer to leave the home or requires inpatient treatment.
    3. Suspected, probable, or confirmed Lyme disease per 2011 CDC Lyme Disease National Surveillance Case Definitions.
    4. Underlying illness that may cause fatigue such as thyroid dysfunction, hepatitis, or other systemic diseases.
  • Additional exclusion criteria for participants with PI-ME/CFS for exercise stress visit

    1. Current (within 1 week) use of prescription or over-the-counter medications, herbal supplements, or nutraceuticals that may influence brain excitability that the potential participant is either unwilling or clinically unable to safely wean off for the duration of the period of the exercise stress visit. The possibility for a potential participant to be weaned off medication will be cooperatively determined by both the clinical investigative team and personal physicians. Examples of medications that influence brain excitability include tricyclic antidepressants, hypnotic, antiepileptic, antipsychotic medication, stimulants, antihistamines, muscle relaxants, dopaminergic medications, and sleep medications.

  • Additional exclusion criteria for healthy volunteer group

    1. Substantial daily fatigue as determined using PROMIS-SF Fatigue: score of > 17.
    2. Significant neurological disorder (e.g. neurodegenerative disorder, stroke, epilepsy).
    3. Current (within 1 week) use of prescription or over-the-counter medications, herbal supplements, or nutraceuticals that may influence brain excitability
  • Additional exclusion criteria for Documented Lyme Infection - Asymptomatic group

    1. Substantial daily fatigue as determined using the Multidimensional Fatigue Inventory (MFI): score of > 8 on the general fatigue subscale or >6 on the reduced activity subscale.
    2. Significant neurological disorder (e.g. neurodegenerative disorder, stroke, epilepsy).
    3. Symptoms or diagnosis of Post-Lyme Disease Syndrome
    4. Current (within 1 week) use of prescription or over-the-counter medications, herbal supplements, or nutraceuticals that may influence brain excitability
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02669212

Contacts
Contact: Angelique Gavin (301) 496-1788 mecfsemail@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Principal Investigator: Avindra Nath, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
  More Information

Additional Information:
Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier: NCT02669212     History of Changes
Other Study ID Numbers: 160058
16-N-0058
Study First Received: January 29, 2016
Last Updated: September 12, 2017

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):
Chronic Fatigue Syndrome
Lyme Disease
Healthy Volunteers
Movement Disorder

Additional relevant MeSH terms:
Syndrome
Fatigue
Fatigue Syndrome, Chronic
Encephalomyelitis
Disease
Pathologic Processes
Signs and Symptoms
Virus Diseases
Muscular Diseases
Musculoskeletal Diseases
Central Nervous System Diseases
Nervous System Diseases
Neuromuscular Diseases
Central Nervous System Infections

ClinicalTrials.gov processed this record on September 21, 2017