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

NCT01411046 | Unknown DMC

• 1 other identifier: GCR-RA-CSI
• Study Type: observational
• Target: 106
• Locations: 1 country
• Sites: 1

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.

Conditions

Rheumatoid Arthritis

Keywords

Glucocorticoid; polymorphism; Glucocorticoid receptor gene; rheumatoid arthritis; adrenal insufficiency; prednisolone treatment

Outcome Measures

Primary Outcomes (1)

• adrenal insufficiency

  test for adrenal function by stimulation test (Synacthen test)

  upon first visit within average 1 month

Secondary Outcomes (4)

• quality of life

  upon inclusion (baseline)

• Bone Density status

  results from latest DXA scan performed in routine settings, bonemarkers upon inclusion (baseline)

• body composition

  upon inclusion (baselline)

• metabolic syndrome

  upon inclusion (baseline)

Study Arms (1)

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

Interventions

Synacthen test DIAGNOSTIC_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).

RA treated with prednisolone

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• Adult patients \> 18 years)
• Caucasian classified with rheumatoid arthritis.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

Rigshospitalet

Copenhagen, 2100, Denmark

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

blood samples and DNA from gene analyses

MeSH Terms

Conditions

Arthritis, Rheumatoid; Adrenal Insufficiency

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Adrenal Gland Diseases; Endocrine System Diseases

Study Officials

• Ulla Feldt-Rasmussen, Professor

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ulla Feldt-Rasmussen, Professor

CONTACT

+45 35451023; ufeldt@rh.dk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 28, 2011
• First Posted: August 5, 2011
• Study Start: April 1, 2011
• Primary Completion: June 1, 2017
• Study Completion: December 1, 2017
• Last Updated: April 28, 2017

Record last verified: 2017-04

Locations

DK (1)