The Role of Glucocorticoid Receptor SNPs in Receptor Function and Metabolic Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01143493
First received: June 11, 2010
Last updated: July 2, 2014
Last verified: November 2013
  Purpose

Background:

- Glucocorticoids are primary stress response hormones released from the adrenal gland when an individual is under stress. Chronic or ongoing elevation of these hormones due to prolonged stress or medical treatments can have numerous harmful effects. Researchers are interested in learning more about how these hormones affect cell growth, development, and death. To study glucocorticoid hormones, researchers plan to use the medication dexamethasone, which affects the parts of cells that respond to glucocorticoid hormones.

Objectives:

- To study glucocorticoid stress hormones in healthy individuals before and after receiving dexamethasone.

Eligibility:

  • Healthy individuals at least 18 years of age.
  • Participants must not be using certain medications that may affect the dexamethasone test, including hormonal contraception, steroid-based drugs, and some antidepressants.

Design:

  • This study will require an initial screening visit and a second study visit. The visits are estimated to require about 1 to 2 hours of participation over a period of up to 14 days.
  • Participants will be screened at visit 1 with a full physical examination and medical history, and an initial blood sample for testing.
  • For visit 2, participants will be asked to abstain from all food and drinks except for water for 12 hours before the appointment, and will take one tablet of dexamethasone 9 hours before the appointment.
  • Participants will have a second blood sample taken during visit 2, and will receive a snack after the blood is drawn.

Condition
Glucose Homeostasis
Protein Metabolism
Lipid Metabolism
Respiratory Function
Connective Tissue Metabolism

Study Type: Observational
Official Title: The Role of Glucocorticoid Receptor SNPs in Receptor Function and Metabolic Disease

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 580
Study Start Date: May 2010
Detailed Description:

STUDY DESIGN:

This in vivo and in vitro observational gene association study will investigate the functional relevance of SNPs in the NR3C1 gene in selected populations. A subgroup of the EPR will be genotyped to identify novel SNPs in the NR3C1 gene. The most promising SNPs for functional relevance in in vitro assays will be examined. Individuals with and without functionally relevant, novel SNPs will be recruited for further study. In part 1, lymphocytes from these participants will be isolated, exposed ex vivo to corticosteroids, and gene expression profiles in response to this stimulus will be compared. In part 2, in vivo effect of these SNPs in steroid responsiveness will be evaluated by performing a modified low dose dexamethasone suppression test comparing by genotype. The study design is innovative as a gene association study in the sense that participants are recruited on the basis of genotype and then the phenotype of each participant is observed.

STUDY DURATION:

It is anticipated that the study will require 48 months to complete participants study visits.

PRIMARY OBJECTIVE:

Investigate in vivo the role of hGR SNPs (hGR9beta A3669B, hGR N363S) in steroid responsiveness by performing a modified dexamethasone suppression test and comparing responses by genotype.

SECONDARY OBJECTIVE:

Investigate the role of hGR SNPs (hGR9beta A3669B, hGR N363S) in human steroid responsiveness by comparing (across genotypes) gene expression profiles of isolated macrophages and lymphocytes exposed ex vivo to corticosteroids.

PRIMARY ENDPOINT:

Measure the change in serum cortisol levels after modified dexamethasone suppression test.

SECONDARY ENDPOINT:

Measure gene expression fold changes by microarray analysis after ex vivo glucocorticoid exposure of macrophages and lymphocytes; validation of affected RNA (elevated or decreased expression) through PCR analysis.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA FOR PART 1 AND 2:
  • Male or female 18 years of age or older at the time of enrollment
  • Must be a participant in the EPR study
  • Are genotyped and determined to be heterozygote or homozygote carriers of one of the two hGR SNPs (hGR9B A3669G and hGR N363S) or are wild type at the SNP location
  • Able to understand and provide written informed consent to participate in the study
  • Able to travel to the CRU
  • Willing and able to fast for periods of up to 12 hours during the study
  • Healthy participants as defined by the International Red Cross guidelines (Healthy means that an individual feels well and can perform normal activities. If the individual has a chronic condition such as diabetes or high blood pressure, healthy also means that they are being treated and the condition is under control).

EXCLUSION CRITERIA:

Exclusion Criteria for Part 1

Participants with the following history will be excluded from part 1 of the study:

  • Any glucocorticoid use within 14 days of scheduled visit 1 including oral, inhaled, nasal sprays, and cream (dermal/mucosal)
  • Pregnant or currently breastfeeding

Exclusion Criteria for Part 2

Participants with the following history will be excluded from part 2 of the study to avoid confounding the dexamethasone suppression test:

  • Any glucocorticoid use within 14 days of scheduled visit 2 including oral, inhaled, nasal sprays, and cream (dermal/mucosal)
  • Pregnant or currently breastfeeding
  • Currently enrolled in another clinical research study and/or is receiving an investigational agent for any reason
  • Does not agree to take dexamethasone at scheduled time
  • Planning to use certain medications such as corticosteroids, estrogens, or tetracyclines prior to the visit 2, because they can affect test results. If the participant is willing to withhold these medications for 14 days, then the participant will be allowed to participate in visit 2.

Participants with the following history will be excluded from part 2 of the study because the dexamethasone may cause potential harm to the participant:

  • Uncontrolled hypertension (high blood pressure of 140/90 mm Hg or above that is not responding to standard medical treatment)
  • Active coronary artery disease (angina) or moderate to severe heart failure stage New York Heart Association III-IV
  • Renal failure
  • Glaucoma
  • Uncontrolled psychiatric disorders such as bipolar disorder or schizoaffective disorder
  • Active systemic fungal infection
  • Prior hypersensitivity reaction to Dexamethasone
  • Currently receiving treatment for cancer (certain cancers, like lung cancer make adrenocorticotropic hormone (ACTH), and all induce stress)
  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: NCT01143493

Contacts
Contact: Lisa B Murphy (919) 541-9839 murphylb@mail.nih.gov
Contact: Stavros Garantziotis, M.D. Not Listed garantziotis@mail.nih.gov

Locations
United States, North Carolina
NIEHS Clinical Research Unit (CRU) Recruiting
Research Triangle Park, North Carolina, United States
Contact: Lisa Murphy    919-541-9839    murphylb@mail.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Stavros Garantziotis, M.D. National Institute of Environmental Health Sciences (NIEHS)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT01143493     History of Changes
Other Study ID Numbers: 100130, 10-E-0130
Study First Received: June 11, 2010
Last Updated: July 2, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Dexamethasone Challenge
Glucocorticoid
Metabolic Disease
NR3C1 Gene
Health Volunteer
HV

Additional relevant MeSH terms:
Metabolic Diseases
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014