protocolSection identificationModule nctId: NCT06305026, orgStudyIdInfo id: S-20190160, briefTitle: Protocol for a Diagnostic Test Accuracy of Histological Muscle and Skin Biopsies of Rheumatoid Arthritis Patients Revealing Objective Chronic Widespread Pain Phenomena Related to Fibromyalgia, statusModule overallStatus: RECRUITING, startDateStruct date: 2024-02-07, primaryCompletionDateStruct date: 2024-08-31, completionDateStruct date: 2024-08-31, studyFirstPostDateStruct date: 2024-03-12, lastUpdatePostDateStruct date: 2024-03-12, sponsorCollaboratorsModule leadSponsor name: Hospital of South West Jutland, class: OTHER, collaborators name: Odense University Hospital, descriptionModule briefSummary: Background: Chronic widespread pain is challenging in the management of the patient with rheumatoid arthritis (RA), affecting approximately one third of this patient population. However, pain is not always caused by disease activity (inflammation) but can be associated to central pain mechanisms as seen in fibromyalgia (FM). FM is characterized by widespread pain and tenderness; often accompanied by disturbed sleep, fatigue, cognitive impairment, emotional distress and multiple symptoms from various organ systems. Among patients with RA the prevalence of concomitant FM is reported to be 12-17% compared to 1-3% in the general population. In general the pain, felt by the fibromyalgia patients is considered to be due to lower pain thresholds because of abnormal central pain processing. Pain reported by RA patients with concomitant FM could potentially be explained by this phenomenon. Little is known about RA patients fulfilling criteria for FM. Muscles-studies of FM patients have not found any histopathological explanation of the pain felt, however an old study of muscle changes in RA patients found changes that could explain muscle pain. Small fiber neuropathy (SFN) is a condition associated with autoimmune diseases, and evidence suggests that SFN is likely to contribute to the pain observed in FM.Objectives: To determine the diagnostic test accuracy (sensitivity and specificity) of both muscle- and skin-biopsies for fibromyalgia phenotyping and detection by clinical referral (RA with concomitant FM) as the reference standard (i.e. fulfilment of 2016 FM criteria).Data collection: Will be done as study subjects are included and stored in REDCAP.Eligibility criteria for participants and settings where the data will be collected: RA patients will be assessed in the daily clinic in Esbjerg and Odense and examined for concomitant FM (I.e. satisfying the 2016 criteria for FM). Patients will afterwards be invited to participate in the study. Inclusion will continue until 25 RA patients fulfilling FM criteria and thus based on the expected prevalence at least 25 (- and maximum 50) RA patients not fulfilling FM critieria has undergone the index tests.Whether participants form a consecutive, random, or convenience series: Participants form a consecutive series.Description of the index test and reference standard: Twenty-five RA patients with concomitant FM and more than 25 (- maximum 50 patients) RA patients not fulfilling FM criteria will undergo the index tests. Muscle and skin biopsies will be performed in each group using standardized techniques. The reference standard will be fulfillment of the 2016 criteria for fibromyalgia.Estimates of diagnostic accuracy and their precision: Regarding muscle- and skin biopsies sensitivity, specificity and positive predictive value will be calculated using two times two table. Regarding skin biopsies, median values in the two groups (RA +/- FM) will be compared using a two-sample t-test., conditionsModule conditions: Rheumatoid Arthritis, conditions: Fibromyalgia, Secondary, conditions: Widespread Chronic Pain, conditions: Muscle Disorder, designModule studyType: OBSERVATIONAL, designInfo observationalModel: CASE_CONTROL, timePerspective: CROSS_SECTIONAL, enrollmentInfo count: 50, type: ESTIMATED, armsInterventionsModule interventions name: Muscle- and skin biopsies, outcomesModule primaryOutcomes measure: Muscle pathology, primaryOutcomes measure: Skin biopsies, secondaryOutcomes measure: Cold pressure test, secondaryOutcomes measure: Pain pressure threshold (PPT), secondaryOutcomes measure: Computerized Cuff pressure algometry (CPA), eligibilityModule sex: ALL, minimumAge: 18 Years, maximumAge: 100 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Esbjerg Hospital, status: RECRUITING, city: Esbjerg, zip: 6700, country: Denmark, contacts name: Philip R LageHansen, MD, role: CONTACT, phone: +4530114582, email: philip.rask.lage-hansen3@rsyd.dk, contacts name: Philip LageHansen, MD, role: PRINCIPAL_INVESTIGATOR, contacts name: Torkell Ellingsen, Professor, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 55.47028, lon: 8.45187, hasResults: False