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

ACTH Clinical Trial

Official title:

Evaluation of Cortisol Resistance in Young Sedentary and Endurance-trained Men and Elderly Sedentary Men

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01294319
• Other study ID #: 110078
• Secondary ID: 11-CH-0078
• Status: Completed
• Phase: Phase 2
• First received: February 10, 2011
• Last updated: October 19, 2017
• Start date: January 24, 2011
• Est. completion date: August 10, 2016

Study information

• Verified date: October 2017
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: August 10, 2016
• Est. primary completion date: August 10, 2016
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 80 Years

Eligibility

• INCLUSION CRITERIA:

Men aged 18 to 30 years of age are required for the young endurance trained and sedentary groups; men aged 65-80 years for the older study group, who will meet criteria for sedentary men below. Women and children are excluded to enhance homogeneity of responses and avoid the influence of menstrual cyclicity on the HPA axis.

Sedentary:

• Less than one hour physical activity per week for three years

• No change in exercise anticipated for 6 weeks

Trained:

• Greater than 45km (28 miles) running per week for at least 3 months

• No change in exercise anticipated for 6 weeks

For all participants:

• All races

• Sleep-wake cycle with sleeping at night, wakening between 5 and 8 AM

• BMI between 18 and 25 kg/M2

• Normal TSH and free T4

EXCLUSION CRITERIA:

For all participants:

• Sleep disorders as assessed by sleep apnea questionnaire

• Smoking

• No more than 2 servings of alcohol daily

• Medications known to affect the HPA axis or steroid metabolism, including narcotics, Glucocorticoids, megace or CYP3A4 modulators

• History of psychiatric or endocrine disorders

• Marijuana or other illicit drug use

• Recent appendicular or skeletal injury

• Uncontrolled hypertension

• Chronic pain requiring daily medication

• Current treatment with medications related to mineralocorticoid function such as potassium, ACE-inhibitors, ARBs, diuretics, spironolactone

• Frailty score of 4-7 on the Canadian Study of Health and Aging frailty scale (Rockman 2005)

• Overtraining syndrome will be an exclusion and will be assessed by questionnaire

• Abnormal creatinine level (greater than 1.2 mg/dl)

• Liver function tests greater than two fold normal

• Benzodiazepine use

Related Conditions & MeSH terms

• ACTH
• Cortisol Resistance
• Glucocorticoid
• Mineralcorticoid
• Negative Feedback

Intervention

Drug:
• Mifepristone

• Placebo

• Spironolactone

• Combined

• Dexamethasone

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Bauer ME. Stress, glucocorticoids and ageing of the immune system. Stress. 2005 Mar;8(1):69-83. Review. — View Citation

Bertagna X, Bertagna C, Luton JP, Husson JM, Girard F. The new steroid analog RU 486 inhibits glucocorticoid action in man. J Clin Endocrinol Metab. 1984 Jul;59(1):25-8. — View Citation

Booth CK, Probert B, Forbes-Ewan C, Coad RA. Australian army recruits in training display symptoms of overtraining. Mil Med. 2006 Nov;171(11):1059-64. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Suppressors After Dexamethasone	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.	cortisol measured between 8 and 9 after dexamethasone was taken between 11 PM and midnight
Secondary	Post-dexamethasone Cortisol Level		Cortisol obtained at 8-9 AM after dexamethasone taken between 11 pm and midnight

External Links

•   NIH Clinical Center Detailed Web Page