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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01294319
First Posted: February 11, 2011
Last Update Posted: November 21, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
  Purpose
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.

Condition Intervention Phase
Cortisol Resistance Negative Feedback ACTH Mineralcorticoid Glucocorticoid Drug: Mifepristone Drug: Placebo Drug: Spironolactone Drug: Combined Drug: Dexamethasone Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Evaluation of Cortisol Resistance in Young Sedentary and Endurance-trained Men and Elderly Sedentary Men

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ):

Primary Outcome Measures:
  • Proportion of Suppressors After Dexamethasone [ Time Frame: 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:
  • Post-dexamethasone Cortisol Level [ Time Frame: Cortisol obtained at 8-9 AM after dexamethasone taken between 11 pm and midnight ]

Enrollment: 51
Study Start Date: January 24, 2011
Study Completion Date: August 10, 2016
Primary Completion Date: August 10, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sedentary young adults, SMCP
Spironolactone, Then Mifepristone, Then Combined, Then Placebo (SMCP), Then Dexamethasone
Drug: Mifepristone
Other Name: Mifepristone 400 MG
Drug: Placebo Drug: Spironolactone
Other Name: Spironolactone 200 MG
Drug: Combined
Other Name: Mifepristone 400 MG and Spironolactone 200 MG
Drug: Dexamethasone
Other Name: Dexamethasone 0.25 mg
Experimental: Endurance-trained young athletes, SMCP
Spironolactone, Then Mifepristone, Then Combined, Then Placebo (SMCP), Then Dexamethasone
Drug: Mifepristone
Other Name: Mifepristone 400 MG
Drug: Placebo Drug: Spironolactone
Other Name: Spironolactone 200 MG
Drug: Combined
Other Name: Mifepristone 400 MG and Spironolactone 200 MG
Drug: Dexamethasone
Other Name: Dexamethasone 0.25 mg
Experimental: Sedentary young adults, MSPC
Mifepristone, Then Spironolactone, Then Placebo, Then Combined (MSPC), Then Dexamethasone
Drug: Mifepristone
Other Name: Mifepristone 400 MG
Drug: Placebo Drug: Spironolactone
Other Name: Spironolactone 200 MG
Drug: Combined
Other Name: Mifepristone 400 MG and Spironolactone 200 MG
Drug: Dexamethasone
Other Name: Dexamethasone 0.25 mg
Experimental: Endurance-trained young athletes, MSPC
Mifepristone, Then Spironolactone, Then Placebo, Then Combined (MSPC), Then Dexamethasone
Drug: Mifepristone
Other Name: Mifepristone 400 MG
Drug: Placebo Drug: Spironolactone
Other Name: Spironolactone 200 MG
Drug: Combined
Other Name: Mifepristone 400 MG and Spironolactone 200 MG
Drug: Dexamethasone
Other Name: Dexamethasone 0.25 mg
Experimental: Sedentary young adults, CPSM
Combined, Then Placebo, Then Spironolactone, Then Mifepristone (CPSM), Then Dexamethasone
Drug: Mifepristone
Other Name: Mifepristone 400 MG
Drug: Placebo Drug: Spironolactone
Other Name: Spironolactone 200 MG
Drug: Combined
Other Name: Mifepristone 400 MG and Spironolactone 200 MG
Drug: Dexamethasone
Other Name: Dexamethasone 0.25 mg
Experimental: Endurance-trained young athletes, CPSM
Combined, Then Placebo, Then Spironolactone, Then Mifepristone (CPSM), Then Dexamethasone
Drug: Mifepristone
Other Name: Mifepristone 400 MG
Drug: Placebo Drug: Spironolactone
Other Name: Spironolactone 200 MG
Drug: Combined
Other Name: Mifepristone 400 MG and Spironolactone 200 MG
Drug: Dexamethasone
Other Name: Dexamethasone 0.25 mg
Experimental: Sedentary young adults,PCMS
Placebo, Then Combined, Then Mifepristone, Then Spironolactone (PCMS), Then Dexamethasone
Drug: Mifepristone
Other Name: Mifepristone 400 MG
Drug: Placebo Drug: Spironolactone
Other Name: Spironolactone 200 MG
Drug: Combined
Other Name: Mifepristone 400 MG and Spironolactone 200 MG
Drug: Dexamethasone
Other Name: Dexamethasone 0.25 mg
Experimental: Endurance-trained young athletes,PCMS
Placebo, Then Combined, Then Mifepristone, Then Spironolactone (PCMS), Then Dexamethasone
Drug: Mifepristone
Other Name: Mifepristone 400 MG
Drug: Placebo Drug: Spironolactone
Other Name: Spironolactone 200 MG
Drug: Combined
Other Name: Mifepristone 400 MG and Spironolactone 200 MG
Drug: Dexamethasone
Other Name: Dexamethasone 0.25 mg

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria
  • 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01294319


Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator: Lynnette K Nieman, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  More Information

Additional Information:
Publications:
Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT01294319     History of Changes
Other Study ID Numbers: 110078
11-CH-0078 ( Other Identifier: National Institutes of Health )
First Submitted: February 10, 2011
First Posted: February 11, 2011
Results First Submitted: August 11, 2017
Results First Posted: November 21, 2017
Last Update Posted: November 21, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ):
Cortical Resistance
ACTH
Glucocorticoid
Mifepristone
SPIRONOLACTONE
Exercise
Hypothalamic-Pituitary-Adrenal Axis
Healthy Volunteer
HV

Additional relevant MeSH terms:
Dexamethasone acetate
Dexamethasone
Hydrocortisone
Mifepristone
Spironolactone
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Abortifacient Agents, Steroidal
Abortifacient Agents
Reproductive Control Agents
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Contraceptives, Postcoital, Synthetic
Contraceptives, Postcoital
Hormone Antagonists