This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

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

This study is currently recruiting participants.
See Contacts and Locations
Verified April 2017 by Ulla Feldt-Rasmussen, Rigshospitalet, Denmark
Sponsor:
Information provided by (Responsible Party):
Ulla Feldt-Rasmussen, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT01411046
First received: July 28, 2011
Last updated: April 26, 2017
Last verified: April 2017
  Purpose
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 Intervention
Rheumatoid Arthritis Diagnostic Test: Synacthen test

Study Type: Observational
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Ulla Feldt-Rasmussen, Rigshospitalet, Denmark:

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


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

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

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

  • 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

Estimated Enrollment: 106
Study Start Date: April 2011
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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).

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.
  Eligibility

Ages Eligible for Study:   18 Years to 90 Years   (Adult, Senior)
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.
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01411046

Contacts
Contact: Ulla Feldt-Rasmussen, Professor +45 35451023 ufeldt@rh.dk

Locations
Denmark
Rigshospitalet Recruiting
Copenhagen, Denmark, 2100
Contact: Ulla Feldt-Rasmussen, Professor    +4535451023    ulla.feldt-rasmussen@dadlnet.dk   
Principal Investigator: Ulla Feldt-Rasmussen, Professor         
Sponsors and Collaborators
Rigshospitalet, Denmark
Investigators
Principal Investigator: Ulla Feldt-Rasmussen, Professor Rigshospitalet, Denmark
  More Information

Responsible Party: Ulla Feldt-Rasmussen, Professor, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT01411046     History of Changes
Other Study ID Numbers: GCR-RA-CSI
Study First Received: July 28, 2011
Last Updated: April 26, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Ulla Feldt-Rasmussen, Rigshospitalet, Denmark:
Glucocorticoid
polymorphism
Glucocorticoid receptor gene
rheumatoid arthritis
adrenal insufficiency
prednisolone treatment

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Adrenal Insufficiency
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Adrenal Gland Diseases
Endocrine System Diseases
Prednisolone acetate
Methylprednisolone acetate
Prednisolone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone hemisuccinate
Prednisolone phosphate
Glucocorticoids
Epinephrine
Racepinephrine
Epinephryl borate
Anti-Inflammatory Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents

ClinicalTrials.gov processed this record on September 21, 2017