Autoimmune Mechanisms in Fibromyalgia

NCT05815381 | Completed

• 1 other identifier: 2019-06161
• Study Type: observational
• Target: 183
• Locations: 1 country
• Sites: 1

Brief Summary

A cohort of fibromyalgia (FM) patients (n =90) and healthy controls (HC) (n= 93) was recruited to investigate the associations between human IgG binding to satellite glia cells (SGC) from dorsal root ganglia (DRG) and pathophysiological mechanisms. The study is based on previously identified mechanisms resulting from injecting human IgG antibodies from FM patients, but not HC, in mice (Goebel et al. J Clin Invest. 2021;131(13):e144201). Subjects have been carefully phenotyped using validated questionnaires and quantitative sensory testing (QST) was applied to determine pain sensitivity. A blood sample was taken to quantify anti-SGC IgG, as well as proteins, lipids and metabolites. Skin biopsies were taken to analyze changes in skin innervation (IENFD) and immune cell activation. Magnetic resonance spectroscopy (MRS) and functional magnetic resonance imaging (fMRI) was performed (n=122) to investigate central nervous system pain related mechanisms. Insular glutamate levels, as well as the levels of other brain metabolites will be determined (MRS) and related to symptom severity and anti-SGC IgG levels. Resting state as well as pain related cerebral activation (BOLD) during standardized evoked pain stimuli will be characterized (fMRI) and related to the MRS findings and to anti-SGC IgG levels.

Conditions

Fibromyalgia

Keywords

Fibromyalgia; Autoimmunity; IgG antibodies; Satellite glia cells

Outcome Measures

Primary Outcomes (8)

• Group differences in anti-SGC IgG levels

  Difference in percent satellite glia cells bound by IgG (anti-SGC IgG levels, 0-100%, 100% worst) between fibromyalgia patients and healthy controls

  2 years

• Resting state cerebral activity and anti-SGC IgG levels in FM

  Difference in resting state functional magnetic resonance imaging (exploratory approach) between fibromyalgia (FM) patients with high (50% or more) and low (less than 50%) percent satellite glia cells bound by IgG (anti-SGC IgG levels)

  2 years

• Cerebral activation during pressure pain (150kPa) and anti-SGC IgG levels in FM

  Difference in blood oxygenation level dependent functional magnetic resonance imaging during evoked pain (150 kPa) between fibromyalgia (FM) patients with high (50% or more) and low (less than 50%) percent satellite glia cells bound by IgG (anti-SGC IgG levels)

  2 years

• Cerebral activation during pressure pain (300kPa) and anti-SGC IgG levels in FM

  Difference in blood oxygenation level dependent functional magnetic resonance imaging during evoked pain (300 kPa) between fibromyalgia (FM) patients with high (50% or more) and low (less than 50%) percent satellite glia cells bound by IgG (anti-SGC IgG levels)

  2 years

• Glutamate concentrations in anterior insula and anti-SGC IgG levels in FM

  Difference in glutamate levels, magnetic resonance spectroscopy of anterior insula, between fibromyalgia (FM) patients with high (50% or more) and low (less than 50%) percent satellite glia cells bound by IgG (anti-SGC IgG levels)

  2 years

• Glutamate concentrations in posterior insula and anti-SGC IgG levels in FM

  Difference in glutamate levels, magnetic resonance spectroscopy of posterior insula between fibromyalgia (FM) patients with high (50% or more) and low (less than 50%) percent satellite glia cells bound by IgG (anti-SGC IgG levels)

  2 years

• Cerebral metabolites in anterior insula and anti-SGC IgG levels in FM

  Differences in magnetic resonance spectroscopy of anterior insula between fibromyalgia (FM) patients with high (50% or more) and low (less than 50%) percent satellite glia cells bound by IgG (anti-SGC IgG levels)(exploratory)

  2 years

• Cerebral metabolites in posterior insula and anti-SGC IgG levels in FM

  Differences in magnetic resonance spectroscopy of posterior insula between fibromyalgia (FM) patients with high (50% or more) and low (less than 50%) percent satellite glia cells bound by IgG (anti-SGC IgG levels)(exploratory)

  2 years

Secondary Outcomes (12)

• Group differences in resting state functional magnetic resonance imaging

  2 years

• Group differences in fMRI BOLD during evoked pressure pain (150 kPa)

  2 years

• Group differences in fMRI BOLD during evoked pressure pain (300 kPa)

  2 years

• Group differences in glutamate levels in anterior insula

  2 years

• Group differences in glutamate levels in posterior insula

  2 years

Other Outcomes (8)

• Correlations between % SGC IgG and IENFD

  2 years

• Correlations between IENFD and glutamate in anterior insula

  2 years

• Correlations between IENFD and glutamate in posterior insula

  2 years

Study Arms (2)

Fibromyalgia patients

Female sex, age 20-65 years and fulfilling the ACR 1990 and ACR 2016 fibromyalgia diagnostic criteria.

Other: Questionnaires, quantitative sensory testing, blood sampling, skin biopsies, functional magnetic resonance imaging, magnetic resonance spectroscopy

Healthy controls

Sex and age matched healthy controls.

Other: Questionnaires, quantitative sensory testing, blood sampling, skin biopsies, functional magnetic resonance imaging, magnetic resonance spectroscopy

Interventions

Questionnaires, quantitative sensory testing, blood sampling, skin biopsies, functional magnetic resonance imaging, magnetic resonance spectroscopy OTHER

se arm/group descriptions

Fibromyalgia patients; Healthy controls

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: female
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects will be recruited by advertising in daily press and social media. All subjects will be pre-screened by a telephone interview from our research nurse regarding inclusion and exclusion criteria before invited to the first visit. All subjects will have to sign informed consent before being included.

You may qualify if:

• Female sex,
• age 20-65 years
• For the FM arm:
• fulfilling the ACR 1990 fibromyalgia diagnostic criteria
• fulfilling the ACR 2016 fibromyalgia diagnostic criteria

You may not qualify if:

• autoimmune or inflammatory diseases (other than FM in the FMS cohort)
• other somatic diseases that could influence the study outcome (e.g. peripheral neuropathy etc)
• pain problems (other than FM in the FMS cohort)
• severe depression/anxiety that requires specific treatments
• medication with anticonvulsants, antidepressants or corticosteroids
• inability to refrain from NSAIDs, analgesics, sedatives or sleep medication 48 hours before examinations
• inability to communicate in Swedish or other factors that the investigator judges would interfere with the participation in the study
• smoking \> 5 cigarettes/day
• pregnancy
• drug or alcohol abuse
• contraindications to skin biopsy (allergy to local anesthetics, hemophilia, medication with anticoagulants)
• contraindications to fMRI (metal implants, pacemaker)

Sponsors & Collaborators

• Karolinska Institutet: lead
• Uppsala University: collaborator
• The Swedish Rheumatism Ass: collaborator
• Region Stockholm: collaborator

Study Sites (1)

Karolinska Insitutet

Stockholm, Sweden

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma, serum, skin biopsies

MeSH Terms

Conditions

Fibromyalgia; Autoimmune Diseases

Interventions

Surveys and Questionnaires; Blood Specimen Collection; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Eva Kosek, Prof

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, senior consultant

Study Record Dates

• First Submitted: November 8, 2022
• First Posted: April 18, 2023
• Study Start: November 16, 2020
• Primary Completion: November 22, 2022
• Study Completion: November 22, 2022
• Last Updated: April 18, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)