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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01411046
• Other study ID #: GCR-RA-CSI
• Status: Recruiting
• Phase: N/A
• First received: July 28, 2011
• Last updated: April 26, 2017
• Start date: April 2011
• Est. completion date: December 2017

Study information

• Verified date: April 2017
• Source: Rigshospitalet, Denmark
• Contact: Ulla Feldt-Rasmussen, Professor
• Phone: +45 35451023
• Email: ufeldt[@]rh.dk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 106
• Est. completion date: December 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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 9ß (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

Related Conditions & MeSH terms

• Adrenal Insufficiency
• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

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).

Locations

Country	Name	City	State
Denmark	Rigshospitalet	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	adrenal insufficiency	test for adrenal function by stimulation test (Synacthen test)	upon first visit within average 1 month
Secondary	quality of life	test by questionnaires	upon inclusion (baseline)
Secondary	Bone Density status	DXA and bone markers	results from latest DXA scan performed in routine settings, bonemarkers upon inclusion (baseline)
Secondary	body composition	BMI, waist-, hip- circumferencia	upon inclusion (baselline)
Secondary	metabolic syndrome	blood lipids, abdominal obesity, blood pressure, fasting plasma glucose	upon inclusion (baseline)