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

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

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.

Study Overview

• Status: Unknown
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Diagnostic test: Synacthen test

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 Type: Observational
• Enrollment (Anticipated): 106

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Rigshospitalet
    • Principal Investigator: Ulla Feldt-Rasmussen, Professor
    • Contact: Ulla Feldt-Rasmussen, Professor; Phone Number: +4535451023; Email: ulla.feldt-rasmussen@dadlnet.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

RA treated with prednisolone; 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; 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).

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Anticipated): June 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: July 28, 2011
• First Submitted That Met QC Criteria: August 4, 2011
• First Posted (Estimate): August 5, 2011

Study Record Updates

• Last Update Posted (Actual): April 28, 2017
• Last Update Submitted That Met QC Criteria: April 26, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: rheumatoid arthritis; polymorphism; prednisolone treatment; Glucocorticoid; adrenal insufficiency; Glucocorticoid receptor gene
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Adrenal Gland Diseases; Arthritis; Arthritis, Rheumatoid; Adrenal Insufficiency
• Other Study ID Numbers: GCR-RA-CSI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided