There is one clinical trial.
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.
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.. 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 secondary null hypotheses are that there are no differences among genotypes in fold-change for expression level (measured by RT-PCR for the genes selected by the microarray analysis as having differential expression), and the two-sided alternative is that there are trends.. - 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. --- A3669G ---
- 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) - Any condition that, in the investigator's opinion, places the participant at undue risk for complications - 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. --- A3669G ---
Description: 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.
Measure: Measure the change in serum cortisol levels after modified dexamethasone suppression test Time: baseline level in first visit, posttreatment level in second visitDescription: The secondary null hypotheses are that there are no differences among genotypes in fold-change for expression level (measured by RT-PCR for the genes selected by the microarray analysis as having differential expression), and the two-sided alternative is that there are trends.
Measure: 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. Time: The cells are cultured from blood drawn from participants at the first clinic visit.