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

• Conditions: Rheumatoid Arthritis
• Interventions: Diagnostic Test: Synacthen test

• Registration Number: NCT01411046
• Lead Sponsor: Rigshospitalet, Denmark

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.

Study Timeline

• Study Start: 2011-04
• Study First Submitted: 2011-07-28
• Study First Submitted QC: 2011-08-04
• Study First Posted: 2011-08-05
• Status Verified: 2017-04
• Last Update Submitted: 2017-04-26
• Last Update Posted: 2017-04-28
• Primary Completion: 2017-06
• Study Completion: 2017-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 106

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
RA treated with prednisolone	Synacthen test	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.

Primary Outcome Measures

Name	Time	Method
adrenal insufficiency	upon first visit within average 1 month	test for adrenal function by stimulation test (Synacthen test)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Rigshospitalet; 🇩🇰 Copenhagen, Denmark