Difference in GC-induced Adrenal Insufficiency in RA Related to Polymorphisms in the Glucocorticoid Receptor Gene

Study Overview
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Brief Summary
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Development of glucocorticoid (GC)-induced adrenal insufficiency is a serious adverse effect of GC treatment. It is today not possible to predict this adverse effect. The project aims at investigating a possible individual aspect, which may render subjects more or less sensitive to glucocorticoids, and thereby influence development of GC induced adrenal insufficiency. The hypothesis is that subjects with one or another of the polymorphisms in the GC receptor gene will either have increased or diminished GC sensitivity. This may be responsible for differences in development of GC induced adrenal insufficiency.

Detailed Description
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Blood is sampled from patients with rheumatoid arthritis (RA), fulfilling the inclusion criteria and patients are genotyped for the SNPs N363S, BclI, ER22/23EK and 9β and grouped according to haplotypes. SNPs will be determined by polymerase chain reaction (PCR). Patients will be included for a Synacthen test, to evaluate their adrenal function. Information from the results of the study will be able to assist clinicians to identify patients at risk and thus individualize GC therapy in a tailored fashion. Results of the study will be important for all patient groups worldwide on GC therapy.

Official Title
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Observational Cohort Study on Difference in Glucocorticoid-induced Adrenal Insufficiency in Patients With Rheumatoid Arthritis Related to Different Sensitivity Polymorphisms in the Glucocorticoid Receptor Gene

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Diagnostic Test: Synacthen test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients > 18 years) Caucasian classified with rheumatoid arthritis. 1987 ACR-classification criteria. Prednisolone min 5mg/day for at least 6 months. Presence of either BclI (high GC sensitivity) or 9β (low GC sensitivity)polymorphisms, or wildtype for for all 4 SNPs studied. Patients with or without these polymorphisms were invited to a Synacthen® test, but patients with a mixed hetero- and homozygote genotype were not Exclusion Criteria: Other major organ disease Females pregnant Females not willing to pause estrogen-containing medications 6 weeks prior to Synacthen® test unable to give a written informed content

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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 |
| --- | --- |
| RA treated with prednisolone<br>Patients with RA treated with prednisolone, minimum 5 mg/day for minimum 6 months. Patients are grouped according to haplotype of 4 SNPs of the glucocorticoid recepror gene. Patients with or without these polymorphisms were invited to a Synacthen® test, but patients with a mixed hetero- and homozygote genotype were not. Adrenal function is evaluated with a Synacthen test. | Diagnostic Test: Synacthen test<br>* 250 microg Synacthen test, performed fasting, in the morning, starting between 08·00 and 10·30 h, after an overnight fast and a prednisolone pause of approximately 48 hours (depending on normal dose administration time).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adrenal insufficiency | test for adrenal function by stimulation test (Synacthen test) | upon first visit within average 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| quality of life | test by questionnaires | upon inclusion (baseline) | 
| Bone Density status | DXA and bone markers | results from latest DXA scan performed in routine settings, bonemarkers upon inclusion (baseline) | 
| body composition | BMI, waist-, hip- circumferencia | upon inclusion (baselline) | 
| metabolic syndrome | blood lipids, abdominal obesity, blood pressure, fasting plasma glucose | upon inclusion (baseline) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucocorticoid, polymorphism, Glucocorticoid receptor gene, rheumatoid arthritis, adrenal insufficiency, prednisolone treatment