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

NCT04263454 | Completed Phase 2 Results FDA Drug

• 1 other identifier: IRB-140930002
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Fibromyalgia

Keywords

neuroinflammation; neuroimaging; fibromyalgia; endotoxin; chronic pain

Outcome Measures

Primary Outcomes (3)

• 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.

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

• 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.

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

• 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.

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

Study Arms (2)

Healthy Control

OTHER

All 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.

Drug: Endotoxin, Escherichia Coli; Procedure: Magnetic Resonance Spectroscopy

Fibromyalgia

EXPERIMENTAL

All 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.

Drug: Endotoxin, Escherichia Coli; Procedure: Magnetic Resonance Spectroscopy

Interventions

Endotoxin, Escherichia Coli DRUG

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

Also known as: Endotoxin

Fibromyalgia; Healthy Control

Magnetic Resonance Spectroscopy PROCEDURE

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

Also known as: MRI

Fibromyalgia; Healthy Control

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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;
• Resting heart rate ≥55
• Supine systolic blood pressure of \<140mmHg and \>100mmHg AND
• Diastolic blood pressure \<90mgHG and \>60mmHg at screening.

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• American Fibromyalgia Syndrome Association: collaborator
• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Fibromyalgia; Neuroinflammatory Diseases; Chronic Pain

Interventions

endotoxin, Escherichia coli; Endotoxins; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Bacterial Toxins; Toxins, Biological; Biological Factors; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Results Point of Contact

• Title: Jarred Younger
• Organization: University of Alabama at Birmingham

youngerlab@uab.edu

205-975-5821

Study Officials

• Jarred M Younger, PhD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Healthy controls and fibromyalgia patients will have an MRI scan both before and 3 hours post endotoxin injection.

Study Record Dates

• First Submitted: February 3, 2020
• First Posted: February 10, 2020
• Study Start: March 11, 2020
• Primary Completion: December 22, 2021
• Study Completion: December 22, 2021
• Last Updated: April 14, 2023
• Results First Posted: April 14, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)