Rheumatoid Arthritis
Conditions
Keywords
Glucocorticoid, polymorphism, Glucocorticoid receptor gene, rheumatoid arthritis, adrenal insufficiency, prednisolone treatment
Brief summary
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
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.
Interventions
DIAGNOSTIC_TESTSynacthen test
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).
Sponsors
Rigshospitalet, Denmark
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| adrenal insufficiency | upon first visit within average 1 month | test for adrenal function by stimulation test (Synacthen test) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bone Density status | results from latest DXA scan performed in routine settings, bonemarkers upon inclusion (baseline) | DXA and bone markers |
| quality of life | upon inclusion (baseline) | test by questionnaires |
| body composition | upon inclusion (baselline) | BMI, waist-, hip- circumferencia |
| metabolic syndrome | upon inclusion (baseline) | blood lipids, abdominal obesity, blood pressure, fasting plasma glucose |
Countries
Denmark
Contacts
Primary ContactUlla Feldt-Rasmussen, Professor
Outcome results
None listed