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

NCT01294319 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 11007811-CH-0078
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

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.

Conditions

Cortisol Resistance; Negative Feedback; ACTH; Mineralcorticoid; Glucocorticoid

Keywords

Cortical Resistance; ACTH; Glucocorticoid; Mifepristone; SPIRONOLACTONE; Exercise; Hypothalamic-Pituitary-Adrenal Axis; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Post-dexamethasone Cortisol Level

  Cortisol obtained at 8-9 AM after dexamethasone taken between 11 pm and midnight

Study Arms (8)

Sedentary young adults, SMCP

EXPERIMENTAL

Spironolactone, Then Mifepristone, Then Combined, Then Placebo (SMCP), Then Dexamethasone

Drug: Mifepristone; Drug: Placebo; Drug: Spironolactone; Drug: Combined; Drug: Dexamethasone

Endurance-trained young athletes, SMCP

EXPERIMENTAL

Spironolactone, Then Mifepristone, Then Combined, Then Placebo (SMCP), Then Dexamethasone

Drug: Mifepristone; Drug: Placebo; Drug: Spironolactone; Drug: Combined; Drug: Dexamethasone

Sedentary young adults, MSPC

EXPERIMENTAL

Mifepristone, Then Spironolactone, Then Placebo, Then Combined (MSPC), Then Dexamethasone

Drug: Mifepristone; Drug: Placebo; Drug: Spironolactone; Drug: Combined; Drug: Dexamethasone

Endurance-trained young athletes, MSPC

EXPERIMENTAL

Mifepristone, Then Spironolactone, Then Placebo, Then Combined (MSPC), Then Dexamethasone

Drug: Mifepristone; Drug: Placebo; Drug: Spironolactone; Drug: Combined; Drug: Dexamethasone

Sedentary young adults, CPSM

EXPERIMENTAL

Combined, Then Placebo, Then Spironolactone, Then Mifepristone (CPSM), Then Dexamethasone

Drug: Mifepristone; Drug: Placebo; Drug: Spironolactone; Drug: Combined; Drug: Dexamethasone

Endurance-trained young athletes, CPSM

EXPERIMENTAL

Combined, Then Placebo, Then Spironolactone, Then Mifepristone (CPSM), Then Dexamethasone

Drug: Mifepristone; Drug: Placebo; Drug: Spironolactone; Drug: Combined; Drug: Dexamethasone

Sedentary young adults,PCMS

EXPERIMENTAL

Placebo, Then Combined, Then Mifepristone, Then Spironolactone (PCMS), Then Dexamethasone

Drug: Mifepristone; Drug: Placebo; Drug: Spironolactone; Drug: Combined; Drug: Dexamethasone

Endurance-trained young athletes,PCMS

EXPERIMENTAL

Placebo, Then Combined, Then Mifepristone, Then Spironolactone (PCMS), Then Dexamethasone

Drug: Mifepristone; Drug: Placebo; Drug: Spironolactone; Drug: Combined; Drug: Dexamethasone

Interventions

Mifepristone DRUG

Also known as: Mifepristone 400 MG

Endurance-trained young athletes, CPSM; Endurance-trained young athletes, MSPC; Endurance-trained young athletes, SMCP; Endurance-trained young athletes,PCMS; Sedentary young adults, CPSM; Sedentary young adults, MSPC; Sedentary young adults, SMCP; Sedentary young adults,PCMS

Placebo DRUG

Endurance-trained young athletes, CPSM; Endurance-trained young athletes, MSPC; Endurance-trained young athletes, SMCP; Endurance-trained young athletes,PCMS; Sedentary young adults, CPSM; Sedentary young adults, MSPC; Sedentary young adults, SMCP; Sedentary young adults,PCMS

Spironolactone DRUG

Also known as: Spironolactone 200 MG

Endurance-trained young athletes, CPSM; Endurance-trained young athletes, MSPC; Endurance-trained young athletes, SMCP; Endurance-trained young athletes,PCMS; Sedentary young adults, CPSM; Sedentary young adults, MSPC; Sedentary young adults, SMCP; Sedentary young adults,PCMS

Combined DRUG

Also known as: Mifepristone 400 MG and Spironolactone 200 MG

Endurance-trained young athletes, CPSM; Endurance-trained young athletes, MSPC; Endurance-trained young athletes, SMCP; Endurance-trained young athletes,PCMS; Sedentary young adults, CPSM; Sedentary young adults, MSPC; Sedentary young adults, SMCP; Sedentary young adults,PCMS

Dexamethasone DRUG

Also known as: Dexamethasone 0.25 mg

Endurance-trained young athletes, CPSM; Endurance-trained young athletes, MSPC; Endurance-trained young athletes, SMCP; Endurance-trained young athletes,PCMS; Sedentary young adults, CPSM; Sedentary young adults, MSPC; Sedentary young adults, SMCP; Sedentary young adults,PCMS

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• Abnormal creatinine level (greater than 1.2 mg/dl)
• Liver function tests greater than two fold normal
• Benzodiazepine use

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Bauer ME. Stress, glucocorticoids and ageing of the immune system. Stress. 2005 Mar;8(1):69-83. doi: 10.1080/10253890500100240.

  PMID: 16019599 BACKGROUND

• 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. doi: 10.1210/jcem-59-1-25.

  PMID: 6327758 BACKGROUND

• 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. doi: 10.7205/milmed.171.11.1059.

  PMID: 17153542 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Motor Activity

Interventions

Mifepristone; Spironolactone; Dexamethasone

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Lactones; Organic Chemicals; Pregnenes; Pregnanes; Pregnadienetriols; Pregnadienes; Steroids, Fluorinated

Results Point of Contact

• Title: Dr. Lynnette Nieman
• Organization: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

niemanl@mail.nih.gov

301-496-4000

Study Officials

• Lynnette K Nieman, M.D.

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2011
• First Posted: February 11, 2011
• Study Start: January 24, 2011
• Primary Completion: August 10, 2016
• Study Completion: August 10, 2016
• Last Updated: July 15, 2024
• Results First Posted: November 21, 2017

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)