The Innate Central Nervous System Immune Response to an Experimental Immune Challenge in People With Fibromyalgia
Condition: Fibromyalgia
MeSH terms: Fibromyalgia; Myofascial Pain Syndromes
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The major goal of this study is to determine if the innate immune response is dysregulated in
      people with fibromyalgia, compared to healthy controls. Magnetic resonance spectroscopy will
      be used to measure changes in the brain's metabolic profile following an experimental immune
      stimulus, to test whether individuals with fibromyalgia show a heightened immune response in
      the brain. The ultimate goal of this research is to better understand the role of brain
      inflammation in the pathophysiology of chronic pain and fatigue, which will guide the
      development of more effective therapies for these conditions.
    

Detailed description: 
      The study consists of two sessions: the screening session and the experimental session.
      During the initial phone screening, individuals who contact the study team will be given
      information about the study, including a description of all study-related procedures. If
      interested, participants will then be taken through a phone screen interview that will ask
      them to report demographic information (date of birth, race, ethnicity), height and weight,
      and list of medical conditions and current medications, surgical history within the past
      year, amount of weekly consumption of alcohol, tobacco products, and illicit substances,
      viral or bacterial infections within the past 3 months, recent vaccines received, and current
      participation in other research. The standard MRI Safety form will be administered to ensure
      participants do not have ferromagnetic implants or other contraindications to MRI (e.g.
      claustrophobia).A self-report will also be administered to ascertain that potential
      fibromyalgia participants meet 2016 American College of Rheumatology (ACR) criteria for
      fibromyalgia. The phone screen is intended to reduce participant burden by identifying
      exclusion criteria without the need to attend at UAB. Participants who meet initial screening
      criteria will be invited to attend an in-person screening visit.

      During the screening visit, participants will go to the Clinical Research Unit (CRU) on the
      15th floor of Jefferson Tower. Participants will be asked to fast prior to this visit.
      Participants will provide written informed consent before any study procedures are initiated.
      Participants will provide a urine sample for pregnancy testing. Vital signs (blood pressure,
      heart rate), aural temperature, height and weight will be measured and recorded. Participants
      will undergo 12-lead electrocardiogram and provide a maximum of 60cc of blood into labeled
      blood collection tubes for screening tests. A tender point exam will be administered to
      assess fibromyalgia symptomatology. The procedure uses a pressure algometer, a hand-held
      instrument with a small rubber tip that is applied to the participant's skin over
      standardized regions of the body (occipital, low cervical, upper trapezius, supraspinatus,
      anterior second rib, lateral epicondyle, gluteal, greater trochanteric, or medial knee).
      Pressure is slowly increased at a constant rate until the participant reports the sensation
      changing from one of pressure to one of pain or discomfort. Participants will complete a
      demographics form , Brief Pain Inventory, Fibromyalgia Impact Questionnaire, Multidimensional
      Fatigue Inventory, and Multiple Abilities Symptom Questionnaire. The blood will be tested by
      the UAB Hospital Labs to ensure that the participant meets the study criteria. The ECG will
      be forwarded to the study physician who will assess for evidence of conduction abnormalities
      or of ischemia. If the blood tests or ECG are abnormal, the study physician will determine if
      the participant should be advised to see their PCP. Following availability of all results
      from the screening visit, participants will be contacted via phone and informed of their
      eligibility to attend the experimental session.

      During the experimental session, the administration of endotoxin, brain imaging, and related
      procedures will be performed at the CRU. No fasting is required prior to this visit, and
      participants will be asked to eat breakfast prior to arrival and will be provided with meal
      suggestions. Baseline vital sign measurements consisting of resting blood pressure and pulse
      rate will be measured and recorded within 60 minutes prior to the start of imaging. ECG and
      pregnancy tests will be repeated and participants will be excluded from participation in the
      session if conduction abnormalities are found (same criteria as used during screening) or if
      participants are found to be pregnant. Participants will undergo MRI imaging for
      approximately 1 hour. Participants will leave the scanner and complete questionnaire measures
      assessing participant's current level of fatigue, pain, and mood symptoms. Grip strength will
      also be assessed. A low dose of endotoxin (0.3ng/kg) will then be administered by the study
      nurse via intravenous infusion. Vital signs will be periodically monitored for the rest of
      the session. Participants will remain in the laboratory for three hours before being placed
      into the MRI scanner to complete a second, identical, imaging session. The self-report
      questionnaire measures and grip strength will be repeated every hour following endotoxin
      administration in order to quantify changes in symptoms due to LPS. To avoid participant
      discomfort and to optimize study integrity, a standardized meal of approximately 600-kcal
      will be provided to each participant between the two MRI sessions, as well as a later snack
      of approximately 200-kcal. The meal is standardized to caloric quantity and timing to offset
      any effects of food intake on the immune response.
    

Intervention name(s): Endotoxin, Escherichia Coli; Magnetic Resonance Spectroscopy
Intervention type(s): Drug; Procedure
Intervention description(s): Endotoxin is a purified lipopolysaccharide prepared from E. coli O:113 and vialed under good manufacturing practice guidelines.; MRI is a non-invasive imaging technique and does not utilize ionizing radiation.
Other intervention name(s): Endotoxin; MRI
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Healthy controls and fibromyalgia patients will have an MRI scan both before and 3 hours post endotoxin injection.
Masking: Triple (Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: neuroinflammation; neuroimaging; fibromyalgia; endotoxin; chronic pain