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

NCT ID: NCT01294319

Last Updated: 2024-07-15

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

51 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-01-24

Study Completion Date

2016-08-10

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Cortisol Resistance Negative Feedback ACTH Mineralcorticoid Glucocorticoid

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Sedentary young adults, SMCP

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

Group Type EXPERIMENTAL

Mifepristone

Intervention Type DRUG

Placebo

Intervention Type DRUG

Spironolactone

Intervention Type DRUG

Combined

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

Endurance-trained young athletes, SMCP

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

Group Type EXPERIMENTAL

Mifepristone

Intervention Type DRUG

Placebo

Intervention Type DRUG

Spironolactone

Intervention Type DRUG

Combined

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

Sedentary young adults, MSPC

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

Group Type EXPERIMENTAL

Mifepristone

Intervention Type DRUG

Placebo

Intervention Type DRUG

Spironolactone

Intervention Type DRUG

Combined

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

Endurance-trained young athletes, MSPC

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

Group Type EXPERIMENTAL

Mifepristone

Intervention Type DRUG

Placebo

Intervention Type DRUG

Spironolactone

Intervention Type DRUG

Combined

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

Sedentary young adults, CPSM

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

Group Type EXPERIMENTAL

Mifepristone

Intervention Type DRUG

Placebo

Intervention Type DRUG

Spironolactone

Intervention Type DRUG

Combined

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

Endurance-trained young athletes, CPSM

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

Group Type EXPERIMENTAL

Mifepristone

Intervention Type DRUG

Placebo

Intervention Type DRUG

Spironolactone

Intervention Type DRUG

Combined

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

Sedentary young adults,PCMS

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

Group Type EXPERIMENTAL

Mifepristone

Intervention Type DRUG

Placebo

Intervention Type DRUG

Spironolactone

Intervention Type DRUG

Combined

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

Endurance-trained young athletes,PCMS

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

Group Type EXPERIMENTAL

Mifepristone

Intervention Type DRUG

Placebo

Intervention Type DRUG

Spironolactone

Intervention Type DRUG

Combined

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Mifepristone

Intervention Type DRUG

Placebo

Intervention Type DRUG

Spironolactone

Intervention Type DRUG

Combined

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Mifepristone 400 MG Spironolactone 200 MG Mifepristone 400 MG and Spironolactone 200 MG Dexamethasone 0.25 mg

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

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

NIH

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Lynnette K Nieman, M.D.

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

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

Reference Type BACKGROUND
PMID: 16019599 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 6327758 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17153542 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

11-CH-0078

Identifier Type: OTHER

Identifier Source: secondary_id

110078

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Effect of Exenatide on Cortisol Secretion
NCT03160261 COMPLETED PHASE4
Hormone and Information Processing Study
NCT00539305 COMPLETED PHASE3