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临床试验/NCT05815381
NCT05815381已完成不适用

Autoimmune Mechanisms in Fibromyalgia

Karolinska Institutet1 个研究点 分布在 1 个国家目标入组 183 人开始时间: 2020年11月16日最近更新:
适应症

试验速览

阶段
不适用
状态
已完成
入组人数
183
试验地点
1
主要终点
Resting state cerebral activity and anti-SGC IgG levels in FM

研究概览

简要总结

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.

详细描述

Visit 1 (duration approx. 2,5-4 hours)

Questionnaires: A check of inclusion and exclusion criteria was made, including the palpation of tender points (ACR 1990 FM criteria). Subjects completed a set of validated questionnaires regarding pain (pain intensity ratings on visual analogue scale (VAS), pain duration, pain drawing, Short form McGill), fibromyalgia severity (fibromyalgia impact questionnaire, (FIQ)), sleep (Pittsburgh Sleep Inventory Questionnaire, (PSQI)), fatigue (Multidimensional Fatigue Inventory (MFI-20)), depression/anxiety (Hospital anxiety depression scale (HADS), Becks depression inventory (BDI), State Trait Anxiety Questionnaire (STAI)), pain coping (Coping Strategy Questionnaire (PCS)), acceptance and flexibility (chronic pain acceptance questionnaire (CPAQ-8), acceptance and action questionnaire (SAAQ)), the Tampa Scale for Kinesiophobia (TSK) and health related quality of life (EQ-5D).

Quantitative sensory testing: Perception thresholds for non-painful and painful heat/cold were examined using a Thermotest. A thermode (2x2cm) was placed at the skin and the temperature was modulated by a computer (0-50 degrees C). The subject signaled the respective perception by pressing a button, which terminated the stimulation. Subjects were instructed to press the button at the sensation of the slightest warmth/cold and when the heat/cold become painful. Sensitivity to suprathreshold heat/cold pain stimuli were determined by asking the subject to press the button when they would rate a pain intensity corresponding to 4 and 7/10. Pain sensitivity to pressure was assessed by pressure algometry at 8 different sites in the body. The subjects were instructed to press a signal button when the pressure turned into the slightest sensation of pain (pressure pain threshold) and when the pain corresponded to 4 and 7/10, respectively.

Blood test: Venous blood tests were taken (maximal volume 50 ml/individual). The levels of human IgG binding to murine satellite glia cells (SGC) will be determined as % SGC binding human IgG. In addition, we will also assess the amount of IgG binding to human DRG sections and possibly also to human SGC (postmortem donors). The blood samples will also be analysed for algogenic and inflammatory substances, lipids and metabolites and immune cell activation, including fluorescence-activated cell sorting (FACS)(in a subgroup). As an extension of the study, IgG antibodies will be purified to evaluate the effect on cell cultures and in the rodent FM model.

Skin biopsies: Two punch skin biopsies (4 mm diameter) were performed at the thigh. The skin was sterilized, and anesthetized using a local anesthetic (10mg/ml Xylocain with adrenalin). If needed the was treated with spongostan/BloodStop and a special plaster (Steri-Strip) was always applied for 7-10 days. The skin will be analyzed regarding morphological changes of intradermal small fibres and IENFD and thick myelinated fibers will be determined. In addition, immune cell activation will be assessed using various methods.

研究设计

研究类型
Observational
观察模型
Case Control
时间视角
Cross Sectional

入排标准

年龄范围
20 Years 至 65 Years(Adult, Older Adult)
性别
Female
接受健康志愿者

入选标准

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

排除标准

  • 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)

结局指标

主要结局

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

时间窗: 2 years

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)

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

时间窗: 2 years

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)

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

时间窗: 2 years

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)

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

时间窗: 2 years

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)

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

时间窗: 2 years

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)

Group differences in anti-SGC IgG levels

时间窗: 2 years

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

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

时间窗: 2 years

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)

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

时间窗: 2 years

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)

次要结局

  • Group differences in resting state functional magnetic resonance imaging(2 years)
  • Correlations between % SGC IgG and pain intensity in FM(2 years)
  • Group differences in cerebral metabolites in posterior insula(2 years)
  • Correlations between % SGC IgG and fibromyalgia severity(2 years)
  • Group differences in fMRI BOLD during evoked pressure pain (150 kPa)(2 years)
  • Group differences in glutamate levels in anterior insula(2 years)
  • Group differences in glutamate levels in posterior insula(2 years)
  • Group differences in cerebral metabolites in anterior insula(2 years)
  • Group differences in fMRI BOLD during evoked pressure pain (300 kPa)(2 years)
  • Correlations between glutamate in anterior insula and anti-SGC IgG levels in FM(2 years)
  • Correlations between % SGC IgG and sensitivity to pressure pain in FM(2 years)
  • Correlations between glutamate in posterior insula and and anti-SGC IgG levels in FM(2 years)

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Eva Kosek

Professor, senior consultant

Karolinska Institutet

研究点 (1)

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