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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01411046
Recruitment Status : Unknown
Verified April 2017 by Ulla Feldt-Rasmussen, Rigshospitalet, Denmark.
Recruitment status was:  Recruiting
First Posted : August 5, 2011
Last Update Posted : April 28, 2017
Information provided by (Responsible Party):
Ulla Feldt-Rasmussen, 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.

Condition or disease Intervention/treatment
Rheumatoid Arthritis 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.

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Study Type : Observational
Estimated Enrollment : 106 participants
Observational Model: Case-Control
Time Perspective: Prospective
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 Start Date : April 2011
Estimated Primary Completion Date : June 2017
Estimated Study Completion Date : December 2017

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).

Primary Outcome Measures :
  1. adrenal insufficiency [ Time Frame: upon first visit within average 1 month ]
    test for adrenal function by stimulation test (Synacthen test)

Secondary Outcome Measures :
  1. quality of life [ Time Frame: upon inclusion (baseline) ]
    test by questionnaires

  2. Bone Density status [ Time Frame: results from latest DXA scan performed in routine settings, bonemarkers upon inclusion (baseline) ]
    DXA and bone markers

  3. body composition [ Time Frame: upon inclusion (baselline) ]
    BMI, waist-, hip- circumferencia

  4. metabolic syndrome [ Time Frame: upon inclusion (baseline) ]
    blood lipids, abdominal obesity, blood pressure, fasting plasma glucose

Biospecimen Retention:   Samples With DNA
blood samples and DNA from gene analyses

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01411046

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Contact: Ulla Feldt-Rasmussen, Professor +45 35451023

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Rigshospitalet Recruiting
Copenhagen, Denmark, 2100
Contact: Ulla Feldt-Rasmussen, Professor    +4535451023   
Principal Investigator: Ulla Feldt-Rasmussen, Professor         
Sponsors and Collaborators
Rigshospitalet, Denmark
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Principal Investigator: Ulla Feldt-Rasmussen, Professor Rigshospitalet, Denmark
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Responsible Party: Ulla Feldt-Rasmussen, Professor, Rigshospitalet, Denmark Identifier: NCT01411046    
Other Study ID Numbers: GCR-RA-CSI
First Posted: August 5, 2011    Key Record Dates
Last Update Posted: April 28, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Ulla Feldt-Rasmussen, Rigshospitalet, Denmark:
Glucocorticoid receptor gene
rheumatoid arthritis
adrenal insufficiency
prednisolone treatment
Additional relevant MeSH terms:
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Arthritis, Rheumatoid
Adrenal Insufficiency
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Adrenal Gland Diseases
Endocrine System Diseases