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

NCT01143493 | Completed

• 2 other identifiers: 10013010-E-0130
• Study Type: observational
• Target: 278
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

Genetic Polymorphism; Glucocorticoid; Health Volunteer; HV

Outcome Measures

Primary Outcomes (1)

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

  The null hypothesis for this endpoint (primary hypothesis for this study) is that there is no difference among genotypes in the change from baseline cortisol level. The two-sided alternative hypothesis is that there is a trend(homozygous wild-type to heterozygous to homozygous for the minor allele) in change from baseline.

  baseline level in first visit, posttreatment level in second visit

Secondary Outcomes (1)

• 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.

  The cells are cultured from blood drawn from participants at the first clinic visit.

Study Arms (6)

Carrier - Other

Carrier hGR N363S Heterozygote

Carrier hGR N363S Homozygote

Carrier hGR9B A3669G Heterozygote

Carrier hGR9B A3669G Homozygote

Control

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• Participants with the following history will be excluded from part 1 of the study:
• Any glucocorticoid use within approximately 14 days of scheduled visit 1 including oral, inhaled, nasal sprays, and cream (dermal/mucosal)
• Pregnant or currently breastfeeding
• Planning to use certain medications because they can affect test results.
• Any condition that, in the investigator's opinion, places the participant at undue risk for complications.
• 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 approximately 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:
• High blood pressure of 160/10 mm Hg or above.
• Active coronary artery disease (angina) or moderate to severe heart failure stage New York Heart Association III-IV
• Renal failure

Sponsors & Collaborators

• National Institute of Environmental Health Sciences (NIEHS): lead

Study Sites (1)

NIEHS Clinical Research Unit (CRU)

Research Triangle Park, North Carolina, United States

Location

Related Publications (3)

• Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids--new mechanisms for old drugs. N Engl J Med. 2005 Oct 20;353(16):1711-23. doi: 10.1056/NEJMra050541. No abstract available.

  PMID: 16236742 BACKGROUND

• DeRijk RH, Schaaf M, de Kloet ER. Glucocorticoid receptor variants: clinical implications. J Steroid Biochem Mol Biol. 2002 Jun;81(2):103-22. doi: 10.1016/s0960-0760(02)00062-6.

  PMID: 12137800 BACKGROUND

• Huizenga NA, Koper JW, de Lange P, Pols HA, Stolk RP, Grobbee DE, de Jong FH, Lamberts SW. Interperson variability but intraperson stability of baseline plasma cortisol concentrations, and its relation to feedback sensitivity of the hypothalamo-pituitary-adrenal axis to a low dose of dexamethasone in elderly individuals. J Clin Endocrinol Metab. 1998 Jan;83(1):47-54. doi: 10.1210/jcem.83.1.4498.

  PMID: 9435415 BACKGROUND

MeSH Terms

Conditions

Respiratory Aspiration

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Stavros Garantziotis, M.D.

  National Institute of Environmental Health Sciences (NIEHS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2010
• First Posted: June 14, 2010
• Study Start: September 30, 2010
• Primary Completion: December 2, 2019
• Study Completion: December 2, 2019
• Last Updated: December 4, 2019

Record last verified: 2019-12

Locations

US (1)