Bio-significance of LPC16:0 in Fibromyalgia

Study Overview
=================
Brief Summary
-----------------
Fibromyalgia (FM) is a very common but mysterious pain disorder characterized by chronic widespread muscular pain. Fatigue, anxiety and depression are common comorbidities. The syndrome is commonly associated with several symptoms, including fatigue, sleeping disturbance, cognitive impairment, and comorbid pain syndrome, especially irritable bowel symptoms and temporomandibular disease. Anxiety and depression are common psychiatric co-morbidies. Daily stress is believed to trigger or aggravate pain conditions. These symptoms can markedly affect patients' quality of life, and even lead to disability. So far, the etiology and pathogenesis are largely unknown, and diagnostic biomarkers and curative treatment remain to be developed. Recent technological advances enable scientists to explore mechanisms by genetic, transcriptomic, proteomic, and metabolomic researches. However, no definitive result has been concluded for clinical practice so far. In this study, the investigators use tailored questionnaires to evaluate fibromyalgia and associated symptoms, including numeric rating scale for soreness, widespread soreness index, Fibromyalgia impact questionnaire, Hospital Anxiety and Depression Scale, and perceived stress scale. The investigators also use metabolomics and lipidomic approach to probe the potential pathophysiology of fibromyalgia. In our prior translation research (PMID: 32907805), the investigators found that excessive LPC16:0 resulting from lipid oxidization inflicts psychological stress-induced chronic non-inflammatory pain via activating ASIC3. In this content, our prior translational research identified a potential nociceptive ligand that causes fibromyalgia symptoms, which is likely to function as biomarkers for diagnosis or disease monitor. In the current clinical investigation, the investigators aim to reversely translate the novel findings in animal studies and validate the bio-significance of LPC16:0 for fibromyalgia with clinical approaches.

Official Title
-----------------
A Clinical Approach to Validate the Biological Significance of LPC16:0 as a Discriminating and Pathogenic Biomarker of Fibromyalgia

Conditions
-----------------
Fibromyalgia, Primary, Pain, Soreness, Muscle, Oxidative Stress, Metabolomics, Lipidomics

Intervention / Treatment
-----------------
* Drug: Pregabalin 150mg, imipramine 25mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Clinical diagnosis of fibromyalgia Exclusion Criteria: Systemic rheumatological or immune disorders (e.g., systemic lupus erythematosus, inflammatory myositis), Systemic use of corticosteroids, Pregnancy, Chronic diseases under poor control Malignancies.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with primary fibromyalgia<br>Adults with complaints of chronic widespread pain at the outpatient department of KMUH were consecutively enrolled over a 5-year period from July 2017 to June 2022. Participants were interviewed by experienced neurologists , and those who fulfilled the 2011 American College of Rheumatology (ACR) criteria for FM were recruited . | Drug: Pregabalin 150mg, imipramine 25mg<br>* Conventional treatment for fibromyalgia was given to patients. Clinical follow-ups with questionnaires and interview were arranged then.<br>|
| Healthy controls<br>Age- and sex-matched subjects without pain and soreness were also prospectively recruited as healthy controls. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Questionnaire: Numeric rating scale (NRS) for pain and soreness | assessment of pain and soreness severity. Score: 0(no symptom)  10 (worst symptom) | Changes from baseline NRS at 2 weeks are assessed | 
| Questionnaire: Numeric rating scale (NRS) for pain and soreness | assessment of pain and soreness severity. Score: 0(no symptom)  10 (worst symptom) | Changes from baseline NRS at 4 weeks are assessed | 
| Questionnaire: widespread pain index and widespread soreness index | assessment of pain and soreness diffuseness. Score: 0(no symptom)  19 (mostly diffused symptom) | Change from baseline widespread index at 2 weeks are assessed | 
| Questionnaire: widespread pain index and widespread soreness index | assessment of pain and soreness diffuseness. Score: 0(no symptom)  19 (mostly diffused symptom) | Change from baseline widespread index at 4 weeks are assessed | 
| Questionnaire: Fibromyalgia impact questionnaire (FIQR) | assessment of fibromyalgia impacts and disease severity. Score: 0(no symptom)  100 (worst symptom) | Change from baseline FIQR at 2 weeks are assessed | 
| Questionnaire: Fibromyalgia impact questionnaire (FIQR) | assessment of fibromyalgia impacts and disease severity. Score: 0(no symptom)  100 (worst symptom) | Change from baseline FIQR at 4 weeks are assessed | 
| Questionnaire: Hospital Anxiety and Depression Scale (HADS) | assessment of psychological distress. Score: 0 (no symptom)  42 (worst symptom) | Change from baseline HADS at 2 weeks are assessed | 
| Questionnaire: Hospital Anxiety and Depression Scale (HADS) | assessment of psychological distress. Score: 0 (no symptom)  42 (worst symptom) | Change from baseline HADS at 4 weeks are assessed | 
| Questionnaire: The Pittsburgh Sleep Quality Index (PSQI) | assessment of sleep quality. Score: 0 (no symptom)  21 (worst sleep quality) | Change from baseline PSQI at 2 weeks are assessed | 
| Questionnaire: The Pittsburgh Sleep Quality Index (PSQI) | assessment of sleep quality. Score: 0 (no symptom)  21 (worst sleep quality) | Change from baseline PSQI at 4 weeks are assessed | 
| Questionnaire: Perceived stress scale (PSS) | assessment of perceived stress loading. Score: 0 (no stress)  40 (highest stressed level) | Change from baseline PSS at 2 weeks are assessed | 
| Questionnaire: Perceived stress scale (PSS) | assessment of perceived stress loading. Score: 0 (no stress)  40 (highest stressed level) | Change from baseline PSS at 4 weeks are assessed | 
| Metabolomics investigation | Laboratory investigation of metabolomic expression, including lactate, creatine, malondialdehyde, protein carbonyls and amino acids. | Change from baseline metabolomics at 3 months are assessed | 
| Lipidomics investigation | Laboratory investigation of lipidomic expression, including phosphocholine, sphingomyelin, lysophosphatidylcholine and ceramide. | Change from baseline metabolomics at 3 months are assessed | 
| Metabolomics investigation | Laboratory investigation of metabolomic expression, including lactate, creatine, malondialdehyde, protein carbonyls and amino acids. | Change from baseline metabolomics at 6 months are assessed | 
| Lipidomics investigation | Laboratory investigation of lipidomic expression, including phosphocholine, sphingomyelin, lysophosphatidylcholine and ceramide. | Change from baseline metabolomics at 6 months are assessed | 
| Metabolomics investigation | Laboratory investigation of metabolomic expression, including lactate, creatine, malondialdehyde, protein carbonyls and amino acids. | Change from baseline metabolomics at 9 months are assessed | 
| Lipidomics investigation | Laboratory investigation of lipidomic expression, including phosphocholine, sphingomyelin, lysophosphatidylcholine and ceramide. | Change from baseline metabolomics at 9 months are assessed | 
| Metabolomics investigation | Laboratory investigation of metabolomic expression, including lactate, creatine, malondialdehyde, protein carbonyls and amino acids. | Change from baseline metabolomics at 12 months are assessed | 
| Lipidomics investigation | Laboratory investigation of lipidomic expression, including phosphocholine, sphingomyelin, lysophosphatidylcholine and ceramide. | Change from baseline metabolomics at 12 months are assessed | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
fibromyalgia, lysophosphotidylcholine, pain, soreness, metabolomics