Conditions: Cortisol Resistance Negative Feedback ACTH Mineralcorticoid Glucocorticoid
Keywords: Cortical Resistance ACTH Glucocorticoid Mifepristone SPIRONOLACTONE Exercise Hypothalamic-Pituitary-Adrenal Axis Healthy Volunteer HV
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 51
Healthy volunteers: no

Brief summary:
This study proposes to examine multiple aspects of the hypothalamic-pituitary-adrenal axis in younger endurance trained and sedentary men, and in older sedentary men.

Detailed description:
Adrenocorticotropin (ACTH) secretion is normally exquisitely regulated through endogenous stimulation by corticotrophin-releasing hormone (CRH) and negative feedback inhibition by cortisol, resulting in a circadian rhythm of cortisol. Recent evidence suggests that older men, and younger men who are endurance-trained athletes, both have reduced sensitivity to negative feedback, and perhaps increased basal levels of cortisol and ACTH. To investigate these possibilities, we propose to examine multiple aspects of the hypothalamic-pituitary-adrenal axis in younger endurance trained and sedentary men, and in older sedentary men.

Subjects will collect saliva during two evenings before additional testing, and will on the same evening collect urine for twelve hours, both for cortisol measurements. Blood samples will be collected to evaluate the response to dexamethasone. We also will assess ACTH and cortisol responses to medications that reduce negative inhibition of ACTH. This testing will occur in the evening and will include administration of the glucocorticoid antagonist mifepristone, the mineralocorticoid antagonist spironolactone, and/or a look-alike tablet, on four occasions.

Arms:
arm 1: Spironolactone, Then Mifepristone, Then Combined, Then Placebo (SMCP), Then Dexamethasone arm 2: Spironolactone, Then Mifepristone, Then Combined, Then Placebo (SMCP), Then Dexamethasone arm 3: Mifepristone, Then Spironolactone, Then Placebo, Then Combined (MSPC), Then Dexamethasone arm 4: Mifepristone, Then Spironolactone, Then Placebo, Then Combined (MSPC), Then Dexamethasone arm 5: Combined, Then Placebo, Then Spironolactone, Then Mifepristone (CPSM), Then Dexamethasone arm 6: Combined, Then Placebo, Then Spironolactone, Then Mifepristone (CPSM), Then Dexamethasone arm 7: Placebo, Then Combined, Then Mifepristone, Then Spironolactone (PCMS), Then Dexamethasone arm 8: Placebo, Then Combined, Then Mifepristone, Then Spironolactone (PCMS), Then Dexamethasone

Interventions: intervention 1: Mifepristone intervention 2: Placebo intervention 3: Spironolactone intervention 4: Combined intervention 5: Dexamethasone
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: None

Protocol document: