Evaluation of Cortisol Resistance in Young Sedentary and Endurance-Trained Men

Phase 2

Completed

Conditions: Negative Feedback
ACTH
Cortisol Resistance
Mineralcorticoid
Glucocorticoid

Interventions: Drug: Mifepristone
Drug: Placebo
Drug: Spironolactone
Drug: Combined
Drug: Dexamethasone

Registration Number: NCT01294319

Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 51

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Endurance-trained young athletes, SMCP	Mifepristone	Spironolactone, Then Mifepristone, Then Combined, Then Placebo (SMCP), Then Dexamethasone
Endurance-trained young athletes, SMCP	Placebo	Spironolactone, Then Mifepristone, Then Combined, Then Placebo (SMCP), Then Dexamethasone
Endurance-trained young athletes, SMCP	Spironolactone	Spironolactone, Then Mifepristone, Then Combined, Then Placebo (SMCP), Then Dexamethasone
Sedentary young adults, MSPC	Dexamethasone	Mifepristone, Then Spironolactone, Then Placebo, Then Combined (MSPC), Then Dexamethasone
Sedentary young adults, SMCP	Mifepristone	Spironolactone, Then Mifepristone, Then Combined, Then Placebo (SMCP), Then Dexamethasone
Sedentary young adults, SMCP	Placebo	Spironolactone, Then Mifepristone, Then Combined, Then Placebo (SMCP), Then Dexamethasone
Sedentary young adults, SMCP	Spironolactone	Spironolactone, Then Mifepristone, Then Combined, Then Placebo (SMCP), Then Dexamethasone
Sedentary young adults, SMCP	Combined	Spironolactone, Then Mifepristone, Then Combined, Then Placebo (SMCP), Then Dexamethasone
Sedentary young adults, SMCP	Dexamethasone	Spironolactone, Then Mifepristone, Then Combined, Then Placebo (SMCP), Then Dexamethasone
Endurance-trained young athletes, SMCP	Combined	Spironolactone, Then Mifepristone, Then Combined, Then Placebo (SMCP), Then Dexamethasone
Endurance-trained young athletes, SMCP	Dexamethasone	Spironolactone, Then Mifepristone, Then Combined, Then Placebo (SMCP), Then Dexamethasone
Sedentary young adults, MSPC	Mifepristone	Mifepristone, Then Spironolactone, Then Placebo, Then Combined (MSPC), Then Dexamethasone
Sedentary young adults, MSPC	Placebo	Mifepristone, Then Spironolactone, Then Placebo, Then Combined (MSPC), Then Dexamethasone
Sedentary young adults, MSPC	Combined	Mifepristone, Then Spironolactone, Then Placebo, Then Combined (MSPC), Then Dexamethasone
Endurance-trained young athletes, MSPC	Mifepristone	Mifepristone, Then Spironolactone, Then Placebo, Then Combined (MSPC), Then Dexamethasone
Endurance-trained young athletes, MSPC	Placebo	Mifepristone, Then Spironolactone, Then Placebo, Then Combined (MSPC), Then Dexamethasone
Endurance-trained young athletes, MSPC	Spironolactone	Mifepristone, Then Spironolactone, Then Placebo, Then Combined (MSPC), Then Dexamethasone
Endurance-trained young athletes, MSPC	Combined	Mifepristone, Then Spironolactone, Then Placebo, Then Combined (MSPC), Then Dexamethasone
Endurance-trained young athletes, MSPC	Dexamethasone	Mifepristone, Then Spironolactone, Then Placebo, Then Combined (MSPC), Then Dexamethasone
Sedentary young adults, CPSM	Placebo	Combined, Then Placebo, Then Spironolactone, Then Mifepristone (CPSM), Then Dexamethasone
Sedentary young adults, CPSM	Spironolactone	Combined, Then Placebo, Then Spironolactone, Then Mifepristone (CPSM), Then Dexamethasone
Sedentary young adults, CPSM	Combined	Combined, Then Placebo, Then Spironolactone, Then Mifepristone (CPSM), Then Dexamethasone
Sedentary young adults, CPSM	Dexamethasone	Combined, Then Placebo, Then Spironolactone, Then Mifepristone (CPSM), Then Dexamethasone
Endurance-trained young athletes, CPSM	Mifepristone	Combined, Then Placebo, Then Spironolactone, Then Mifepristone (CPSM), Then Dexamethasone
Endurance-trained young athletes, CPSM	Placebo	Combined, Then Placebo, Then Spironolactone, Then Mifepristone (CPSM), Then Dexamethasone
Endurance-trained young athletes, CPSM	Spironolactone	Combined, Then Placebo, Then Spironolactone, Then Mifepristone (CPSM), Then Dexamethasone
Endurance-trained young athletes, CPSM	Combined	Combined, Then Placebo, Then Spironolactone, Then Mifepristone (CPSM), Then Dexamethasone
Endurance-trained young athletes, CPSM	Dexamethasone	Combined, Then Placebo, Then Spironolactone, Then Mifepristone (CPSM), Then Dexamethasone
Sedentary young adults,PCMS	Mifepristone	Placebo, Then Combined, Then Mifepristone, Then Spironolactone (PCMS), Then Dexamethasone
Sedentary young adults,PCMS	Placebo	Placebo, Then Combined, Then Mifepristone, Then Spironolactone (PCMS), Then Dexamethasone
Sedentary young adults,PCMS	Spironolactone	Placebo, Then Combined, Then Mifepristone, Then Spironolactone (PCMS), Then Dexamethasone
Sedentary young adults,PCMS	Combined	Placebo, Then Combined, Then Mifepristone, Then Spironolactone (PCMS), Then Dexamethasone
Sedentary young adults,PCMS	Dexamethasone	Placebo, Then Combined, Then Mifepristone, Then Spironolactone (PCMS), Then Dexamethasone
Endurance-trained young athletes,PCMS	Mifepristone	Placebo, Then Combined, Then Mifepristone, Then Spironolactone (PCMS), Then Dexamethasone
Endurance-trained young athletes,PCMS	Placebo	Placebo, Then Combined, Then Mifepristone, Then Spironolactone (PCMS), Then Dexamethasone
Endurance-trained young athletes,PCMS	Spironolactone	Placebo, Then Combined, Then Mifepristone, Then Spironolactone (PCMS), Then Dexamethasone
Endurance-trained young athletes,PCMS	Combined	Placebo, Then Combined, Then Mifepristone, Then Spironolactone (PCMS), Then Dexamethasone
Endurance-trained young athletes,PCMS	Dexamethasone	Placebo, Then Combined, Then Mifepristone, Then Spironolactone (PCMS), Then Dexamethasone
Sedentary young adults, MSPC	Spironolactone	Mifepristone, Then Spironolactone, Then Placebo, Then Combined (MSPC), Then Dexamethasone
Sedentary young adults, CPSM	Mifepristone	Combined, Then Placebo, Then Spironolactone, Then Mifepristone (CPSM), Then Dexamethasone

Primary Outcome Measures

Name	Time	Method
Proportion of Suppressors After Dexamethasone	cortisol measured between 8 and 9 after dexamethasone was taken between 11 PM and midnight	All subjects will take 0.25mg dexamethasone as an outpatient between 2300 and 2400h and will then report to the clinic by 0800h next day for the final visit. At the final visit, cortisol response to dexamethasone suppression was assessed. The cortisol response was dichotomized (suppression vs. non-suppression, using 1.8 ug/dL as the cutoff point) and compared between the two groups,Sedentary Young Adults and Endurance-trained Young Athletes.

Secondary Outcome Measures