Improved Diagnostics and Monitoring of Polymyalgia Rheumatica
- Conditions
- Giant Cell ArteritisPolymyalgia RheumaticaAdrenal Insufficiency
- Interventions
- Diagnostic Test: PET/CT
- Registration Number
- NCT04519580
- Lead Sponsor
- Kresten Krarup Keller
- Brief Summary
Background: Polymyalgia rheumatica (PMR) is characterised by pain of the proximal muscles, general symptoms, and raised inflammatory markers. Treatment with prednisolone has several adverse effects. PMR is an exclusion diagnosis, and methods to diagnose and monitor the disease are lacking.
Objective: To investigate if ultrasound and PET/CT can be used to diagnose and monitor PMR. In addition, the importance of prednisolone induced adrenal insufficiency is investigated.
Methods: It is a prospective observational study in patients suspected of PMR. Patients diagnosed with PMR continue in the study. Ultrasound and PET/CT are performed at baseline, after 8 weeks on prednisolone, and after 10 weeks during a short prednisolone break. Adrenal insufficiency is investigated five times throughout the study. After one year the PMR diagnosis is confirmed.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 98
- Patients suspected of PMR.
- Age above 50
- Pain of the proximal muscles.
- Peroral, intraarticular, intramuscular and dermal application of glucocorticoids within the last 3 month.
- Previous prednisolone treatment for GCA/PMR
- Unable to give consent.
- Symptoms of GCA (headache, jaw claudication, vision disturbances).
- Active malignant cancers within the last 5 years (except basal cell carcinoma).
- Other inflammatory rheumatic diseases (eg. rheumatoid arthritis, polymyositis, spondyloarthritis, psoriatic arthritits, gout).
- Uncontrolled diseases (eg severe active astma, cardiac disease with NYHA class IV)
- Treatment with peroral oestrogens, aminogluthethimid, trilostan, ketoconazole, fluconazol, etomidate, phenobarbital, phenytoin, rifampicin, metyrapon, mitotane.
- Known primary or secondary adrenal insufficiency.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Patients with suspected polymyalgia rheumatica PET/CT The study investigates patients with suspected polymyalgia rheumatica (PMR). For Patients where the PMR diagnosis is dismissed, the study terminates after the first visit. Patients diagnosed with PMR will be treated with prednisolone with taper corresponding to usual care. At baseline all patients will have medical history taken, physical examination, blood drawn, Synacthen® test, PET/CT, and ultrasound performed. Physical examination, PET/CT, and ultrasound are repeated after 8 weeks of prednisolone treatment while the patients iare on 10 mg prednisolone as well as after prednisolone taper two weeks later, where Synachten® test is also performed. After 10 weeks prednisolone is restarted at 10 mg and the patient is followed by their general practitioner or at the department of rheumatology, where prednisolone is tapered according to usual care. Patients are invited to a follow up visit after one year.
- Primary Outcome Measures
Name Time Method PMR diagnosis at baseline with PET/CT Baseline Sensitivity and specificity of PET/CT for PMR diagnosis at baseline with the clinical diagnosis after 1 year as reference standard and patients not diagnosed with PMR serving as controls.
- Secondary Outcome Measures
Name Time Method Change in clinical parameters week 8. 8 weeks Change in clinical parameters from baseline to week 8.
Frequency of GCA 12 months Frequency of GCA at diagnosis and during follow up
Change in expression levels of clock gene mRNA as marker of prednisolone-induced changes in sleep, lipid levels and glycated hemoglobin. 1 year Change in expression levels of clock gene mRNA as marker of prednisolone-induced changes in sleep, lipid levels and glycated hemoglobin.
Percentage of patients receiving prednisolone after 3 and 5 years. 5 Years Percentage of patients receiving prednisolone after 3 and 5 years.
PET/CT measures at baseline as a predictor of prednisolone treatment after 3 and 5 years. 5 Years PET/CT measures at baseline is measured with Standard Uptake Value and dichrotone evaluation for PMR (PMR +/-)
Change in PET/CT parameters from baseline to week 8 weeks Change in PET/CT parameters from baseline to week 8.
Presence of adrenal insufficiency at week 10 as a predictor of prednisolone cessation at one year. 12 months Presence of adrenal insufficiency at week 10 as a predictor of prednisolone cessation at one year.
Change in clinical parameters week 10. 10 weeks Change in clinical parameters from week 8 to week 10.
Change in PROM's from week 8 to week 10. 10 weeks Change in PROM's from week 8 to week 10.
Sensitivity and specificity of CRP for PMR diagnosis at week 10. 10 weeks Sensitivity and specificity of CRP for PMR diagnosis at week 10.
Level of inflammatory markers in PMR patients at baseline vs. week 8. 8 weeks Level of inflammatory markers in PMR patients at baseline vs. week 8.
PMR diagnosis at week 8 with PET/CT 8 weeks Sensitivity and specificity of PET/CT for PMR diagnosis at week 8 with the clinical diagnosis after 1 year as reference standard and patients not diagnosed with PMR serving as controls.
Frequency of adrenal insufficiency at week 10. 10 weeks Frequency of adrenal insufficiency at week 10.
Change in PROM's from baseline to week 8. 8 weeks Change in PROM's from baseline to week 8.
Change in PROM's from baseline to 1 year. 12 months Change in PROM's from baseline to 1 year.
Adrenal insufficiency as a predictor of prednisolone treatment after 3 and 5 years. 5 Years Adrenal insufficiency (+/-) will be evaluated with synachten test 4-5 times during the first 1,5 year of the study. At least one positive value will contribute to the parameter.
Changes in US findings from baseline to week 8 as predictor of prednisolone treatment after 3 and 5 years 5 Years Ultrasound dichrotone changes from baseline to week 8 will be evaluated (positive/negative for bursitis/artritis)
Change in Ultrasound parameters from baseline to week 8 8 weeks Change in presence and thickness of subdeltoid bursitis and biceps tenosynovitis from baseline to week 8.
Change in PET/CT parameters from week 8 to week 10. 10 weeks Change in PET/CT parameters from week 8 to week 10.
Frequency of adrenal insufficiency 18 months Frequency of adrenal insufficiency after 1 and 1.5 years.
Level of inflammatory markers in PMR patients vs. non PMR patients at baseline. Baseline Level of inflammatory markers in PMR patients vs. non PMR patients at baseline.
Changes in PET/CT parameters from baseline to week 8 as predictor of prednisolone treatment after 3 and 5 years 5 Years PET/CT changes from baseline to 8 weeks in Standard Uptake Value and dichrotone evaluation for PMR (PMR +/-) will be evaluated.
PMR diagnosis at week 10 with PET/CT 10 weeks Sensitivity and specificity of PET/CT for PMR diagnosis after one week of discontinuation of glucocorticoids (week 10) with the clinical diagnosis after 1 year as reference standard and patients not diagnosed with PMR serving as controls.
Change in Ultrasound parameters from week 8 to week 10 10 weeks Change in presence and thickness of subdeltoid bursitis and biceps tenosynovitis from week 8 to week 10.
Lean boyd weight 18 months Lean body weight adjusted prednisolone dose as a predictor of adrenal insufficiency.
Hypercortisolism as predictor of adrenal insufficiency. 18 months Clinical and biochemical signs of hypercortisolism as predictor of adrenal insufficiency.
Percentage of patients with concomitant GCA and PMR after 3 and 5 years. 5 Years Percentage of patients with concomitant GCA and PMR after 3 and 5 years.
Presence of adrenal insufficiency at week 10 as a predictor of relapse at week 10. 10 weeks Presence of adrenal insufficiency at week 10 as a predictor of relapse at week 10.
Trial Locations
- Locations (3)
Department of Rheumatology, Aarhus University Hospital
🇩🇰Aarhus, Denmark
Department of Rheumatology, Horsens Regional Hospital
🇩🇰Horsens, Denmark
Diagnostic Centre, Silkeborg Regional Hospital
🇩🇰Silkeborg, Denmark