Clinical trial NCT01411046: Difference in GC-induced Adrenal Insufficiency in RA Related to Polymorphisms in the Glucocorticoid Receptor Gene
Official title: 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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Rheumatoid Arthritis
Keywords: Glucocorticoid
polymorphism
Glucocorticoid receptor gene
rheumatoid arthritis
adrenal insufficiency
prednisolone treatment
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2011-08-05
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Consecutive patients with rheumatoid arthritis in prednioslone treatment, screened for four specific polymorphisms of the glucocorticoid receptor gene.

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.

Eligibility criteria: 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

Primary outcomes:
measure: adrenal insufficiency
timeFrame: upon first visit within average 1 month
Secondary outcomes:
measure: quality of life
timeFrame: upon inclusion (baseline)
measure: Bone Density status
timeFrame: results from latest DXA scan performed in routine settings, bonemarkers upon inclusion (baseline)
measure: body composition
timeFrame: upon inclusion (baselline)
measure: metabolic syndrome
timeFrame: upon inclusion (baseline)
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
Study officials:
affiliation: Rigshospitalet, Denmark
name: Ulla Feldt-Rasmussen, Professor
role: PRINCIPAL_INVESTIGATOR
References: