Cortisol ResistancePhase 2NCT01294319
Evaluation of Cortisol Resistance in Young Sedentary and Endurance-Trained Men
A Phase 2 study testing Mifepristone, Spironolactone and Combined in people with Cortisol Resistance and Negative Feedback, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years, men only
- Conditions the study is for
- Cortisol Resistance, Negative Feedback, ACTH
- What is being tested?
- Mifepristone, Spironolactone and Combined
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 51 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Jan 2011to 10 Aug 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 12Show fewer
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Evaluation of Cortisol Resistance in Young Sedentary and Endurance-trained Men and Elderly Sedentary Men
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.
Read the 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.
- Conditions
- Cortisol Resistance, Negative Feedback, ACTH, Mineralcorticoid, Glucocorticoid
- Being tested
- Mifepristone, Placebo, Spironolactone, Combined, Dexamethasone
- Keywords
- Cortical Resistance, ACTH, Glucocorticoid, Mifepristone, SPIRONOLACTONE, Exercise, Hypothalamic-Pituitary-Adrenal Axis, Healthy Volunteer, HV
- Medical subject headings
- Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MifepristoneDrug
Also called Mifepristone 400 MG
PlaceboDrug
SpironolactoneDrug
Also called Spironolactone 200 MG
CombinedDrug
Also called Mifepristone 400 MG and Spironolactone 200 MG
DexamethasoneDrug
Also called Dexamethasone 0.25 mg
| Study group | Role | What they receive |
|---|---|---|
| Sedentary young adults, SMCP | Experimental | Spironolactone, Then Mifepristone, Then Combined, Then Placebo (SMCP), Then Dexamethasone Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: Mifepristone; Drug: Placebo; Drug: Spironolactone; Drug: Combined; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: cortisol measured between 8 and 9 after dexamethasone was taken between 11 PM and midnight
Secondary outcomes (1)
Post-dexamethasone Cortisol Level
Measured: Cortisol obtained at 8-9 AM after dexamethasone taken between 11 pm and midnight
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2011 (estimated)
- Study start24 Jan 2011
- Primary completion10 Aug 2016
- Study completion10 Aug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cortisol ResistanceStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Lynnette K Nieman, M.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01294319
- Sponsor's protocol ID
- 110078
- Other IDs
- 11-CH-0078
- Status last verified
- Jul 2024
- First submitted
- 10 Feb 2011
- Last updated
- 15 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bauer ME. Stress, glucocorticoids and ageing of the immune system. Stress. 2005 Mar;8(1):69-83. doi: 10.1080/10253890500100240.
PubMed 16019599Bertagna 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.
PubMed 6327758Booth 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.
PubMed 17153542
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Cortisol Resistance in Young Sedentary and Endurance-trained Men and Elderly Sedentary Men
- ClinicalTrials.gov ID
- NCT01294319
- Acronym / sponsor ID
- 110078
- Conditions
- Cortisol Resistance, Negative Feedback, ACTH, Mineralcorticoid, Glucocorticoid
- Keywords
- Cortical Resistance, ACTH, Glucocorticoid, Mifepristone, SPIRONOLACTONE, Exercise, Hypothalamic-Pituitary-Adrenal Axis, Healthy Volunteer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- 24 Jan 2011
- Primary completion
- 10 Aug 2016 (actual)
- Study completion
- 10 Aug 2016 (actual)
- First posted
- 11 Feb 2011 (estimated)
- Results
- Posted 21 Nov 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Sedentary young adults, SMCP | Experimental | Drug: Mifepristone, Drug: Placebo, Drug: Spironolactone, Drug: Combined, Drug: DexamethasoneSpironolactone, Then Mifepristone, Then Combined, Then Placebo (SMCP), Then Dexamethasone |
| Endurance-trained young athletes, SMCP | Experimental | Drug: Mifepristone, Drug: Placebo, Drug: Spironolactone, Drug: Combined, Drug: DexamethasoneSpironolactone, Then Mifepristone, Then Combined, Then Placebo (SMCP), Then Dexamethasone |
| Sedentary young adults, MSPC | Experimental | Drug: Mifepristone, Drug: Placebo, Drug: Spironolactone, Drug: Combined, Drug: DexamethasoneMifepristone, Then Spironolactone, Then Placebo, Then Combined (MSPC), Then Dexamethasone |
| Endurance-trained young athletes, MSPC | Experimental | Drug: Mifepristone, Drug: Placebo, Drug: Spironolactone, Drug: Combined, Drug: DexamethasoneMifepristone, Then Spironolactone, Then Placebo, Then Combined (MSPC), Then Dexamethasone |
| Sedentary young adults, CPSM | Experimental | Drug: Mifepristone, Drug: Placebo, Drug: Spironolactone, Drug: Combined, Drug: DexamethasoneCombined, Then Placebo, Then Spironolactone, Then Mifepristone (CPSM), Then Dexamethasone |
| Endurance-trained young athletes, CPSM | Experimental | Drug: Mifepristone, Drug: Placebo, Drug: Spironolactone, Drug: Combined, Drug: DexamethasoneCombined, Then Placebo, Then Spironolactone, Then Mifepristone (CPSM), Then Dexamethasone |
| Sedentary young adults,PCMS | Experimental | Drug: Mifepristone, Drug: Placebo, Drug: Spironolactone, Drug: Combined, Drug: DexamethasonePlacebo, Then Combined, Then Mifepristone, Then Spironolactone (PCMS), Then Dexamethasone |
| Endurance-trained young athletes,PCMS | Experimental | Drug: Mifepristone, Drug: Placebo, Drug: Spironolactone, Drug: Combined, Drug: DexamethasonePlacebo, Then Combined, Then Mifepristone, Then Spironolactone (PCMS), Then Dexamethasone |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
- Less than one hour physical activity per week for three years
- No change in exercise anticipated for 6 weeks
- Greater than 45km (28 miles) running per week for at least 3 months
- No change in exercise anticipated for 6 weeks
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MifepristoneAlso: Mifepristone 400 MG | 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 |
| 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 |
| SpironolactoneAlso: Spironolactone 200 MG | 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 |
| CombinedAlso: Mifepristone 400 MG and Spironolactone 200 MG | 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 |
| DexamethasoneAlso: Dexamethasone 0.25 mg | 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 |
Primary outcome
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.
1 secondary outcome
Post-dexamethasone Cortisol Level
Time frame: Cortisol obtained at 8-9 AM after dexamethasone taken between 11 pm and midnight
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16019599Bauer ME. Stress, glucocorticoids and ageing of the immune system. Stress. 2005 Mar;8(1):69-83. doi: 10.1080/10253890500100240.
- Background: PubMed 6327758Bertagna 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.
- Background: PubMed 17153542Booth 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Cortisol Resistance
Recruiting
IMPACT-MACS: Adrenalectomy vs Semaglutide for Metabolic Outcomes in Mild Autonomous Cortisol Secretion
Mild Autonomous Cortisol Secretion (MACS), Autonomous Cortisol Secretion (ACS)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lynnette K Nieman, M.D. principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mifepristone, Spironolactone and Combined in people with Cortisol Resistance and Negative Feedback, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Suppressors After Dexamethasone (time frame: cortisol measured between 8 and 9 after dexamethasone was taken between 11 PM and midnight). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01294319, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2024; AzTrials last refreshed its copy on 26 Oct 2026.