Improved Diagnostics and Monitoring of Polymyalgia Rheumatica

Study Overview
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Brief Summary
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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.

Official Title
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Improved Diagnostics and Monitoring of Polymyalgia Rheumatica

Conditions
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Polymyalgia Rheumatica, Giant Cell Arteritis, Adrenal Insufficiency

Intervention / Treatment
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* Diagnostic Test: PET/CT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients suspected of PMR. Age above 50 Pain of the proximal muscles. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with suspected polymyalgia rheumatica<br>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. | Diagnostic Test: PET/CT<br>* FDG-PET/CT at baseline, week 8 and week 10.<br>* Other names: Ultrasound;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PMR diagnosis at baseline with PET/CT | 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. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PMR diagnosis at week 8 with PET/CT | 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. | 8 weeks | 
| PMR diagnosis at week 10 with PET/CT | 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. | 10 weeks | 
| Change in Ultrasound parameters from baseline to week 8 | Change in presence and thickness of subdeltoid bursitis and biceps tenosynovitis from baseline to week 8. | 8 weeks | 
| Change in Ultrasound parameters from week 8 to week 10 | Change in presence and thickness of subdeltoid bursitis and biceps tenosynovitis from week 8 to week 10. | 10 weeks | 
| Change in PET/CT parameters from baseline to week | Change in PET/CT parameters from baseline to week 8. | 8 weeks | 
| Change in PET/CT parameters from week 8 to week 10. | Change in PET/CT parameters from week 8 to week 10. | 10 weeks | 
| Frequency of adrenal insufficiency at week 10. | Frequency of adrenal insufficiency at week 10. | 10 weeks | 
| Presence of adrenal insufficiency at week 10 as a predictor of prednisolone cessation at one year. | 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 relapse at week 10. | Presence of adrenal insufficiency at week 10 as a predictor of relapse at week 10. | 10 weeks | 
| Frequency of adrenal insufficiency | Frequency of adrenal insufficiency after 1 and 1.5 years. | 18 months | 
| Lean boyd weight | Lean body weight adjusted prednisolone dose as a predictor of adrenal insufficiency. | 18 months | 
| Hypercortisolism as predictor of adrenal insufficiency. | Clinical and biochemical signs of hypercortisolism as predictor of adrenal insufficiency. | 18 months | 
| Change in clinical parameters week 8. | Change in clinical parameters from baseline to week 8. | 8 weeks | 
| Change in clinical parameters week 10. | Change in clinical parameters from week 8 to week 10. | 10 weeks | 
| Frequency of GCA | Frequency of GCA at diagnosis and during follow up | 12 months | 
| Change in PROM's from baseline to week 8. | Change in PROM's from baseline to week 8. | 8 weeks | 
| Change in PROM's from week 8 to week 10. | Change in PROM's from week 8 to week 10. | 10 weeks | 
| Change in PROM's from baseline to 1 year. | Change in PROM's from baseline to 1 year. | 12 months | 
| Sensitivity and specificity of CRP for PMR diagnosis at week 10. | Sensitivity and specificity of CRP for PMR diagnosis at week 10. | 10 weeks | 
| Level of inflammatory markers in PMR patients at baseline vs. week 8. | Level of inflammatory markers in PMR patients at baseline vs. week 8. | 8 weeks | 
| Level of inflammatory markers in PMR patients vs. non PMR patients at baseline. | Level of inflammatory markers in PMR patients vs. non PMR patients at baseline. | Baseline | 
| Change in expression levels of clock gene mRNA as marker of prednisolone-induced changes in sleep, lipid levels and glycated hemoglobin. | Change in expression levels of clock gene mRNA as marker of prednisolone-induced changes in sleep, lipid levels and glycated hemoglobin. | 1 year | 
| Percentage of patients with concomitant GCA and PMR after 3 and 5 years. | Percentage of patients with concomitant GCA and PMR after 3 and 5 years. | 5 Years | 
| Percentage of patients receiving prednisolone after 3 and 5 years. | Percentage of patients receiving prednisolone after 3 and 5 years. | 5 Years | 
| PET/CT measures at baseline as a predictor of prednisolone treatment after 3 and 5 years. | PET/CT measures at baseline is measured with Standard Uptake Value and dichrotone evaluation for PMR (PMR +/-) | 5 Years | 
| Changes in PET/CT parameters from baseline to week 8 as predictor of prednisolone treatment after 3 and 5 years | PET/CT changes from baseline to 8 weeks in Standard Uptake Value and dichrotone evaluation for PMR (PMR +/-) will be evaluated. | 5 Years | 
| Adrenal insufficiency as a predictor of prednisolone treatment after 3 and 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. | 5 Years | 
| Changes in US findings from baseline to week 8 as predictor of prednisolone treatment after 3 and 5 years | Ultrasound dichrotone changes from baseline to week 8 will be evaluated (positive/negative for bursitis/artritis) | 5 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Positron emission computed tomography, Ultrasound