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https://clinicaltrials.gov/ct2/show/NCT02669212
Name:
Myalgic Encephalomyelitis Chronic Fatigue at the National Institutes of Health
ClinicalTrials.gov Identifier:
NCT02669212
First received: January 29, 2016
Last updated: December 6, 2016
Last verified: October 2016
Further study details as provided by National Institutes of Health Clinical Center (CC):
Primary Outcome Measures:
Secondary Outcome Measures:
Estimated Enrollment: 186
Study Start Date: January 2016
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 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 186 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.
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:
Eligibility
Ages Eligible for Study: 18 Years to 60 Years (Adult)
Genders Eligible for Study: Both
Accepts Healthy Volunteers: Yes
Criteria
Name:
Myalgic Encephalomyelitis Chronic Fatigue at the National Institutes of Health
ClinicalTrials.gov Identifier:
NCT02669212
First received: January 29, 2016
Last updated: December 6, 2016
Last verified: October 2016
Further study details as provided by National Institutes of Health Clinical Center (CC):
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 ] [ Designated as safety issue: No ]
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. ] [ Designated as safety issue: No ]
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: 186
Study Start Date: January 2016
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 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 186 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.
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:
- Characterization of the immune system and inflammatory signaling in blood and cerebrospinal fluid (CSF)
- Characterization of the pattern of microbiome in gut, blood and CSF
- Characterization of physical and cognitive fatigue using functional magnetic resonance imaging and transcranial magnetic stimulation
- Effect of maximal exertion on neurocognition
- Effect of maximal exertion on brain function and connectivity
- Effect of maximal exertion on markers of immune dysfunction and inflammation
- Effect of maximal exertion on metabolic function
- Effect of maximal exertion on autonomic function
- Effect of maximal exertion on gene expression profiles in blood and CSF
Ages Eligible for Study: 18 Years to 60 Years (Adult)
Genders Eligible for Study: Both
Accepts Healthy Volunteers: Yes
Criteria
- INCLUSION CRITERIA:
- Inclusion criteria for all participants
- Adult participants aged 18-60 years at the time of enrollment.
- Self-reported completion of at least the 7th grade of school.
- Ability to speak, read, and understand English.
- Willing and able to complete all study procedures
- Participant has a primary care physician at the time of enrollment.
- Able to provide informed consent.
- Additional inclusion criteria for participants with PI-ME/CFS for the phenotyping visit
- 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.
- 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.
- 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
- Be unanimously considered to be a case of PI-ME/CFS by the protocol s adjudication committee.
- Meet the 1994 Fukuda Criteria and the 2003 Canadian Consensus Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
- 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
- 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/):
- 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.
- 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.
- 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:
- 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/):
- Exclusion criteria for all participants
- Active infection (e.g. influenza, urinary tract infection) by history, physical examination, or laboratory evaluations at the time of enrollment
- Current or past psychotic disorder including depression with psychosis, bipolar disorder, and schizophrenia
- 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
- 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
- Current suicidal ideation
- History of head injury with loss of consciousness, or history of head injury with amnesia lasting greater than a few seconds
- Women who are pregnant, actively seeking to become pregnant, or have been pregnant in the year prior to study enrollment.
- Current or previous malignancy. Certain dermatologic malignancies (e.g. basal cell carcinoma) will be allowed.
- Current immunologic disorder (e.g. Type 1 diabetes, rheumatoid arthritis)
- 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
- 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).
- 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.
- Inability to perform the bicycling exercise task.
- Clinically significant claustrophobia
- Not willing to allow for research samples to be shared with other researchers.
- 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
- Significant neurological disorder (e.g. neurodegenerative disorder, stroke, epilepsy).
- PI-ME/CFS disease severity that makes it impossible for the volunteer to leave the home or requires inpatient treatment.
- Suspected, probable, or confirmed Lyme disease per 2011 CDC Lyme Disease National Surveillance Case Definitions.
- Underlying illness that may cause fatigue such as thyroid dysfunction, hepatitis, or other systemic diseases.
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