Clinical trial NCT06011512: Risk of Diabetes Mellitus in Patients With Giant Cell Arthritis and Polymyalgia Rheumatica.
Official title: Risk of Diabetes Mellitus in Patients With Giant Cell Arthritis and Polymyalgia Rheumatica.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Giant Cell Arteritis
Polymyalgia Rheumatica
Large Vessel Vasculitis
Lead sponsor: Aalborg University Hospital
Sponsor class: OTHER
First posted: 2023-08-25
Enrollment: 800
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The population from which the cohort will be selected from, are patients who are treated at their respective outpatient rheumatology clinic. At least 8 departments of rheumatlogy in Denmark are expected to include patients.

Brief summary: The goal of this observational study is to expand the knowledge about development and aggreviation of diabetes mellitus in patients with giant cell arthritis and polymyalgia rheumatica.

The main questions it aims to answer are:

* To identify the risk of comorbidities, especially diabetes, in patients with giant cell arthritis and polymyalgia rheumatica, treated with glucocorticoids in combination with or without interleukin-6 inhibitor.
* To identify clinical outcomes and biomarkers as potential predictors for development or aggregation of already existing diabetes mellitus in patients with giant cell arthritis or polymyalgia rheumatica using machine learning prediction.

Participants will be followed at their respective rheumatology clinic, and will be asked to deliver blood samples at predefined visits.

Detailed description: The cohort study is a prospective national cohort study in patients with giant cell arthritis (GCA) and polymyalgia rheumatica (PMR). At baseline and follow-up visits at month 1, 3, 6, 12, and every year while patients are treated at departments of rheumatology, collection of demographics, clinical data, patient reported outcomes and blood samples (Regionernes blod- og GenomBank) will occur.

Trial procedure:

Diagnostic information and referral history:

At enrollment, patients will be registered as either incident (first visit within 3 months from diagnosis) or prevalent. The patients diagnosis, time of diagnosis, type of physician establishing diagnosis, time of symptom onset, time of referral, time of first visit, date of prednisolone start, initial prednisolone dose, basis for diagnosis (clinical, classification criteria, biochemical, ultrasound, PET/CT, other imaging modalities, temporal artery biopsy), fulfillment of 1990 ACR classification criteria for GCA, fulfillment of 2018 DCVAS classification criteria for GCA, fulfillment of 2012 EULAR PMR classification criteria will be recorded. Disease stratification will be performed according to clinical diagnosis and imaging test results available. Accordingly, patients will be categorized as either 'GCA', 'PMR', 'GCA and PMR'. If a GCA diagnosis is established, patients will be further categorized as 'c-GCA', 'LV-GCA'

Clinical evaluation:

At each visit, physician disease activity category; remission, potential relapse without treatment escalation, relapse (treatment escalation, refractory disease) will be recorded. Any relapse, that lead to treatment intensification since last study visit, will be recorded. If a relapse is suspected at the current visit, the findings supporting the suspicion of disease activity and the therapeutic consequence, will be recorded.

Demography:

The patients age, gender, height, weight and history of smoking and alcohol consumption will be recorded at enrollment.

Medication:

At each visit current dose of prednisolone, methotrexate or IL-6i treatment are recorded. Date of start and discontinuation and reason for discontinuation of immunosuppressive therapy will be recorded.

Adverse events and treatment related disease burden:

Adverse effects that cause change in treatment strategy will be recorded.

DM:

At each visit data regarding development of diabetes, aggreviation of exciting DM, HgbA1c and blood glucose will be recorded.

Patient reported outcome measures (PROMs): At each visit patients will be asked to report

* Patient global numerical rang scale (NRS, 0-10)
* Patient pain NRS, neck, shoulder, pelvic, thigh (0-10)
* Patient pain NRS headache (0-10)
* Duration of morning stiffness (minutes)
* Morning stiffness NRS (0-10)
* European Quality of life -5dimension5-levels (EQ-5D-5L)

Laboratory test:

Routine blood analysis, including CRP and HbA1c, will be performed as standard of care and according to the National Danish GCA and PMR management guideline \[5\]. At each visit, CRP will be recorded. HbA1c and time of analysis of HbA1c can be recorded at any visit. Additionally, biobank blood samples will be collected at each study visit (study-related procedure):

* 1 × EDTA plasma tube (lavender-top), 9 ml
* 1 × Full blood DNA, 1.5 ml
* 2 × EDTA plasma, 2 ml
* 1 × EDTA buffy coat,
* 2 × serum tube (red-top), 9 ml
* 4 × serum tube, 2 ml

Time of blood sampling will be recorded. A time frame of ± 2 weeks from time of study visit will be accepted for CRP and biobank samples. However, collection of planned blood samples at any study visit, where a relapse is suspected, is strived for before treatment escalation. Furthermore, CD36, sCD36, homeostatic model assessment for insulin resistance (HOMA-IR), proinsulin C-peptide, fasting proinsulin C-peptide and fasting blood glucose are of special interest. For a subgroup of patients, oral glucose tolerance test will be performed. Biomarkers will be analysed at Aalborg University Hospital in collaboration with department of Clinical Biochemistry. Data will be gathered from Aalborg university hospital and in order to strengthen the study, further data from other departments of rheumatology will be requested from the DANIVAS database (Danish national database of patients with GCA and PMR).

Patient data can be collected at any time during their disease course.

Type of visits performed:

* Enrolment visit: First visit
* Follow up visits:
* Treatment response visit: Visits scheduled 1-2 months after treatment start or intensification to assess the effect of treatment.
* Planned follow up
* Suspected relapse or adverse events visit: An extra visit on the suspicion of relapse or adverse events potentially requiring treatment adjustment.

Eligibility criteria: Inclusion Criteria:

* Men or women aged 50 to 85 years
* Are diagnosed with GCA or PMR
* Diagnosis is established by or confirmed by a rheumatologist (clinical expert opinion)
* Speak and understand Danish
* Are able to give signed and dated informed consent

Exclusion Criteria:

* None

Primary outcomes:
measure: Proportion of participants developing diabetes mellitus during the study period, measured in changes of HbA1c.
timeFrame: At baseline, and month 1, 3, 6, 12, 24 and 36.
Secondary outcomes:
measure: Changes in CD36.
timeFrame: At baseline, and month 1, 3, 6, 12, 24 and 36.
measure: Changes in sCD36.
timeFrame: At baseline, and month 1, 3, 6, 12, 24 and 36.
measure: Changes in homeostatic model assessment for insulin resistance.
timeFrame: At baseline, and month 1, 3, 6, 12, 24 and 36.
measure: Changes in proinsulin C-peptide.
timeFrame: At baseline, and month 1, 3, 6, 12, 24 and 36.
measure: Changes in fasting proinsulin C-peptide.
timeFrame: At baseline, and month 1, 3, 6, 12, 24 and 36.
measure: Changes in fasting blood glucose.
timeFrame: At baseline, and month 1, 3, 6, 12, 24 and 36.
measure: Changes in CRP.
timeFrame: At baseline, and month 1, 3, 6, 12, 24 and 36.
measure: Changes in patient pain numerical rating scale, neck, shoulder, pelvic, thigh (0-10).
timeFrame: At baseline, and month 12, 24, 36, 48, and 60.
measure: Changes in patient pain numerical rating scale headache (0-10).
timeFrame: At baseline, and month 12, 24, 36, 48, and 60.
measure: Changes in duration of morning stiffness.
timeFrame: At baseline, and month 12, 24, 36, 48, and 60.
measure: Changes in morning stiffness numerical rating scale (0-10).
timeFrame: At baseline, and month 12, 24, 36, 48, and 60.
measure: Changes in European Quality of life-5dimension5-levels
timeFrame: At baseline, and month 12, 24, 36, 48, and 60.
measure: Duration and cumulative glucocorticoid dosage
timeFrame: At baseline, and month 1, 3, 6, 12, 24 and 36.
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
state: Nordjylland
Study officials:
affiliation: Aalborg University Hospital
name: Salome Kristensen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: