Improved Diagnostics and Monitoring of Polymyalgia Rheumatica

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Giant Cell Arteritis; Polymyalgia Rheumatica; Adrenal Insufficiency
• Intervention / Treatment: Diagnostic test: PET/CT

• Study Type: Observational
• Enrollment (Actual): 98

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Department of Rheumatology, Aarhus University Hospital
  • Horsens, Denmark, 8700
    • Department of Rheumatology, Horsens Regional Hospital
  • Silkeborg, Denmark, 8600
    • Diagnostic Centre, Silkeborg Regional Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The study will include patients suspected for PMR.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients with suspected polymyalgia rheumatica; 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; FDG-PET/CT at baseline, week 8 and week 10.; Other Names: Ultrasound

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Kresten Krarup Keller
• Collaborators: Aarhus University Hospital
• Investigators: Principal Investigator: Kresten Keller, MD, Department of Rheumatology, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2020
• Primary Completion (Actual): July 4, 2023
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: August 17, 2020
• First Submitted That Met QC Criteria: August 17, 2020
• First Posted (Actual): August 19, 2020

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 28, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Ultrasound; Positron emission computed tomography
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Endocrine System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Muscular Diseases; Vasculitis; Skin Diseases, Vascular; Vasculitis, Central Nervous System; Adrenal Gland Diseases; Polymyalgia Rheumatica; Giant Cell Arteritis; Arteritis; Adrenal Insufficiency
• Other Study ID Numbers: IMPROVE PMR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No