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FibromyalgiaPhase 2/3NCT04263454

The Innate Central Nervous System Immune Response to an Experimental Immune Challenge in People With Fibromyalgia

A Phase 2/3 study testing Endotoxin, Escherichia Coli and Magnetic Resonance Spectroscopy in people with Fibromyalgia, run by University of Alabama at Birmingham at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 55 years, women onlyHealthy volunteers can take part
Conditions the study is for
Fibromyalgia
What is being tested?
Endotoxin, Escherichia Coli and Magnetic Resonance Spectroscopy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
1 siteUnited States
Study dates
11 Mar 2020to 22 Dec 2021
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Female;
  • Age 18-55, inclusive;
  • Adequate English for study participation;
  • (fibromyalgia group only) Meet 2010 American College of Rheumatology criteria for the diagnosis of fibromyalgia
  • Able to undergo IV cannulation and to provide the requisite blood samples;
  • BMI 18-39.9 inclusive;
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  • Resting heart rate ≥55
  • Supine systolic blood pressure of <140mmHg and >100mmHg AND
  • Diastolic blood pressure <90mgHG and >60mmHg at screening.

Who cannot join

  • Cardiovascular, immune or infectious disease (e.g. HIV, HCV), or diabetes;
  • At screening, a 12-lead ECG demonstrating QTc>450 or QRS >120msec. If the QTc exceeds 450msec, or QRS exceeds 120msec, the ECG will be repeated x2 and the median of the three values will be used to determine the participant's eligibility.
  • Rheumatologic or autoimmune disease;
  • Vaccine administered within 4 weeks of study participation;
  • Viral or bacterial illness requiring medical attention and/or antibiotics within 3 months of study participation, or any illness or fever within 1 month of study participation;
  • Surgical procedure within 3 months of study participation;
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  • Regular use of anti-inflammatory of immunomodulatory drugs (occasional use of NSAIDs is not an exclusion as long as the participant does not administer within 5 days of study participation);
  • Current use of opioid medication;
  • Current smoker or ceased smoking ≤12 months prior to participation;
  • High alcohol consumption;
  • Consumption of drugs of abuse (except alcohol);
  • Significant psychological comorbidity that in the discretion of the investigator compromises study integrity;
  • Current participation in any other research;
  • Ongoing litigation or worker's compensation claim;
  • Hospital Anxiety and Depression score indicating clinically significant depression;
  • Currently pregnant or positive screening urine pregnancy test;
  • Complete blood count values outside the normal clinical ranges, erythrocyte sedimentation rate (ESR) >60, C-reactive protein (CRP) >3, positive rheumatoid factor (RHF), or positive antinuclear antibodies (ANA).

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

Other trials in United States

About this study

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.

Read the 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.

Conditions
Fibromyalgia
Being tested
Endotoxin, Escherichia Coli, Magnetic Resonance Spectroscopy
Keywords
neuroinflammation, neuroimaging, fibromyalgia, endotoxin, chronic pain
Medical subject headings
Fibromyalgia, Neuroinflammatory Diseases, Chronic Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Endotoxin, Escherichia ColiDrug

    Also called Endotoxin

    Endotoxin is a purified lipopolysaccharide prepared from E. coli O:113 and vialed under good manufacturing practice guidelines.

  • Magnetic Resonance SpectroscopyProcedure or surgery

    Also called MRI

    MRI is a non-invasive imaging technique and does not utilize ionizing radiation.

Study groups in NCT04263454
Study groupRoleWhat they receive
Healthy ControlOtherAll healthy control participants will undergo the same screening and experimental procedures. Healthy controls must report no other medical conditions ( including fibromyalgia) to be considered for inclusion. All healthy controls will have an MRI scan performed both before and 3 hours post 0.4ng/kg endotoxin injection.
Receives: Drug: Endotoxin, Escherichia Coli; Procedure: Magnetic Resonance Spectroscopy
FibromyalgiaExperimentalAll fibromyalgia participants will undergo the same screening and experimental procedures. However, fibromyalgia participants will need to meet 2010 American College of Rheumatology diagnostic criteria for fibromyalgia. All fibromyalgia participants will have an MRI scan performed both before and 3 hours post 0.4ng/kg endotoxin injection.
Receives: Drug: Endotoxin, Escherichia Coli; Procedure: Magnetic Resonance Spectroscopy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Ratio of Choline/ Creatine (CHO/CR) in the Brain From Baseline to 3 Hrs Post-endotoxin Administration

    The concentration of brain metabolite CHO will be measured via MRI scan as a measure of neuroinflammation. This measurement will be performed in both the control and experimental group. Increased CHO is a marker of increased cell turnover that can be seen during neuroinflammation.

    Measured: 3 hours (From Baseline to 3 Hrs Post-endotoxin Administration)

  2. Change in Ratio of Myoinositol/ Creatine (MI/CR) in the Brain From Baseline to 3hrs Post-endotoxin Administration

    The concentration of brain metabolite MI will be assessed via MRI scan as a measure of neuroinflammation. This measurement will be performed in both the control and experimental group. MI is a marker of microglia, and an acute increase in this metabolite could indicate microglia proliferation or accumulation.

    Measured: 3 hours (From Baseline to 3 Hrs Post-endotoxin Administration)

  3. Change in Brain Temperature From Baseline to 3 Hours Post-endotoxin Administration.

    The temperature of the brain will be assessed via MRI scan as a measure of neuroinflammation. This measurement will be performed in both the control and experimental group. Increased brain temperature certain areas may indicate an abnormally increased inflammatory response.

    Measured: 3 hours (From Baseline to 3 Hrs Post-endotoxin Administration)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Feb 2020
  2. Study start11 Mar 2020
  3. Primary completion22 Dec 2021
  4. Study completion22 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Healthy controls and fibromyalgia patients will have an MRI scan both before and 3 hours post endotoxin injection.
Masking
Triple blind
Who is masked
Care provider, Investigator, Outcomes assessor
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04263454
Sponsor's protocol ID
IRB-140930002
Status last verified
Mar 2023
First submitted
3 Feb 2020
Last updated
14 Apr 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Endotoxin, Escherichia Coli and Magnetic Resonance Spectroscopy in people with Fibromyalgia, run by University of Alabama at Birmingham at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Ratio of Choline/ Creatine (CHO/CR) in the Brain From Baseline to 3 Hrs Post-endotoxin Administration (time frame: 3 hours (From Baseline to 3 Hrs Post-endotoxin Administration)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2023.

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