Autonomous Cortisol SecretionPhase 2NCT06106295
Metyrapone for Mild Autonomous Cortisol Secretion (MACS)
A Phase 2 study testing Metyrapone in people with Autonomous Cortisol Secretion and Mild Autonomous Cortisol Secretion (MACS), run by Mayo Clinic at 1 site in United States.
Trial summary
The purpose of this study is to find out whether the study drug, metyrapone, is safe and effective in treating participants with Mild Autonomous Cortisol Secretion (MACS). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Autonomous Cortisol Secretion, Mild Autonomous Cortisol Secretion (MACS)
- What is being tested?
- Metyrapone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Dec 2023to 1 Feb 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provide written informed consent.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Diagnosed with MACS: at least 2 abnormal post-dexamethasone cortisol results (1 mg post-dexamethasone cortisol > 1.8 mcg/d; or 8 mg post-dexamethasone cortisol > 1 mcg/dL) and historical dexamethasone suppression test results can be used if performed within 24 months prior to enrollment.
- Adrenal imaging phenotype consistent with benign disease (adrenal adenoma/s, macronodular or micronodular adrenal hyperplasia).
- At least one of the following comorbidities: obesity (BMI > 30 kg/m^2); dysglycemia; dyslipidemia; hypertension; osteopenia; osteoporosis; fragility fractures.
- Ability to take oral medication and be willing to adhere to the study intervention regimen.
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- For females of reproductive potential: use of highly effective contraception initiated prior to baseline visit and for 1 month after completing metyrapone study.
- For persons of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of <5% per year during the treatment period and for 6 months after the last dose of study treatment.
- Stable timing for bedtime for at least one week prior to on-site study visits
Who cannot join
- Planned alternative therapy for MACS within 6 months after joining the study.
- Current use of oral exogenous glucocorticoid therapy.
- Current use of opioid therapy > 20 MME/day.
- Planned use of oral exogenous glucocorticoid therapy.
- Planned use of opioid therapy > 20 MME/day.
- Use of injectable glucocorticoid within the last 6 weeks.
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- Investigator's judgement based on history/physical examination that a comorbidity or concomitant medication may impact the hypothalamic-pituitary-adrenal axis or steroid metabolome.
- Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia; psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnancy or lactation.
- Known allergic reactions to metyrapone.
- Suspected false positive post-dexamethasone cortisol results due to increased metabolism, poor absorption, or noncompliance with dexamethasone.
- Treatment with another investigational drug or other intervention within lower than specific therapy washout period.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Metyrapone Intervention in Patients With Mild Autonomous Cortisol Secretion (MACS)
The purpose of this study is to find out whether the study drug, metyrapone, is safe and effective in treating participants with Mild Autonomous Cortisol Secretion (MACS).
Read the detailed description
This study will look at how well metyrapone controls blood pressure, blood glucose, blood lipids and weight.
Metyrapone is approved in the United States of America (USA) by the Federal Drug Administration (FDA) for use in the diagnosis of adrenal insufficiency. It is not approved in the USA for the treatment of MACS. It is approved in Europe for the treatment of ACTH dependent Cushing's Syndrome.
Metyrapone is currently being tested to evaluate the safety (side effects/risks) and efficacy (benefits), so its use for the treatment of MACS is experimental in the USA. Its effectiveness is unproven in the USA and metyrapone is considered an investigational study drug in the USA. The Mayo Clinic IRB has given approval for this drug to be used in this setting.
Patients diagnosed with MACS have abnormal cortisol levels above the normal range. Cortisol acts by binding with the cortisol receptors in many tissues of the body. Metyrapone works by reducing cortisol production, thereby decreasing the effects of too much cortisol. Metyrapone doesn't affect levels of other hormones in your body.
- Being tested
- Metyrapone
- Keywords
- Hypercortisolism, Cortisol excess, Cushing syndrome, Adrenal adenoma, Adrenal hyperplasia
- Medical subject headings
- Cushing Syndrome, ACTH Syndrome, Ectopic, Adrenal Hyperplasia, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetyraponeDrug
250 to 1000 milligram (mg) orally in one or two doses in the evening (administered 4 and 2 hours prior to bed)
| Study group | Role | What they receive |
|---|---|---|
| Mild Autonomous Cortisol Secretion (MACS) Open Label Phase and Optional Extension Phase | Experimental | Subjects diagnosed with Mild Autonomous Cortisol Secretion (MACS) will receive metyrapone for a 6 month treatment period (Open Label Phase) with the option to continue for an additional 30 months of metyrapone therapy. If a patient chooses to participate in the Optional Extension Phase they will continue to receive metyrapone therapy until Month 36. This is an additional 30 months of therapy after completion of the Open Label Phase. Receives: Drug: Metyrapone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
Number of participants to experience adverse events
Measured: 50 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2023
- Study start19 Dec 2023
- Primary completion31 Jan 2028 (estimated)
- Study completion1 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autonomous Cortisol SecretionStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Irina Bancos, Mayo Clinic
- Investigators
- Irina Bancos, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06106295
- Sponsor's protocol ID
- 23-008085
- Status last verified
- Sep 2026
- First submitted
- 24 Oct 2023
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metyrapone Intervention in Patients With Mild Autonomous Cortisol Secretion (MACS)
- ClinicalTrials.gov ID
- NCT06106295
- Acronym / sponsor ID
- 23-008085
- Keywords
- Hypercortisolism, Cortisol excess, Cushing syndrome, Adrenal adenoma, Adrenal hyperplasia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 19 Dec 2023 (actual)
- Primary completion
- 31 Jan 2028 (estimated)
- Study completion
- 1 Feb 2028 (estimated)
- First posted
- 30 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to find out whether the study drug, metyrapone, is safe and effective in treating participants with Mild Autonomous Cortisol Secretion (MACS).
Detailed description
This study will look at how well metyrapone controls blood pressure, blood glucose, blood lipids and weight.
Metyrapone is approved in the United States of America (USA) by the Federal Drug Administration (FDA) for use in the diagnosis of adrenal insufficiency. It is not approved in the USA for the treatment of MACS. It is approved in Europe for the treatment of ACTH dependent Cushing's Syndrome.
Metyrapone is currently being tested to evaluate the safety (side effects/risks) and efficacy (benefits), so its use for the treatment of MACS is experimental in the USA. Its effectiveness is unproven in the USA and metyrapone is considered an investigational study drug in the USA. The Mayo Clinic IRB has given approval for this drug to be used in this setting.
Patients diagnosed with MACS have abnormal cortisol levels above the normal range. Cortisol acts by binding with the cortisol receptors in many tissues of the body. Metyrapone works by reducing cortisol production, thereby decreasing the effects of too much cortisol. Metyrapone doesn't affect levels of other hormones in your body.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mild Autonomous Cortisol Secretion (MACS) Open Label Phase and Optional Extension Phase | Experimental | Drug: MetyraponeSubjects diagnosed with Mild Autonomous Cortisol Secretion (MACS) will receive metyrapone for a 6 month treatment period (Open Label Phase) with the option to continue for an additional 30 months of metyrapone therapy. If a patient chooses to participate in the Optional Extension Phase they will continue to receive metyrapone therapy until Month 36. This is an additional 30 months of therapy after completion of the Open Label Phase. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Provide written informed consent.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Diagnosed with MACS: at least 2 abnormal post-dexamethasone cortisol results (1 mg post-dexamethasone cortisol > 1.8 mcg/d; or 8 mg post-dexamethasone cortisol > 1 mcg/dL) and historical dexamethasone suppression test results can be used if performed within 24 months prior to enrollment.
- Adrenal imaging phenotype consistent with benign disease (adrenal adenoma/s, macronodular or micronodular adrenal hyperplasia).
- At least one of the following comorbidities: obesity (BMI > 30 kg/m^2); dysglycemia; dyslipidemia; hypertension; osteopenia; osteoporosis; fragility fractures.
Key exclusion criteria (12 listed)
- Planned alternative therapy for MACS within 6 months after joining the study.
- Current use of oral exogenous glucocorticoid therapy.
- Current use of opioid therapy > 20 MME/day.
- Planned use of oral exogenous glucocorticoid therapy.
- Planned use of opioid therapy > 20 MME/day.
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 |
|---|---|---|
| Metyrapone250 to 1000 milligram (mg) orally in one or two doses in the evening (administered 4 and 2 hours prior to bed) | Drug | Mild Autonomous Cortisol Secretion (MACS) Open Label Phase and Optional Extension Phase |
Primary outcome
Adverse Events
Time frame: 50 months
Number of participants to experience adverse events
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2026.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Irina Bancos, MD principal investigator
Mayo Clinic
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 Metyrapone in people with Autonomous Cortisol Secretion and Mild Autonomous Cortisol Secretion (MACS), run by Mayo Clinic 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 9 inclusion and 12 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: under way, not looking for participants, as of the sponsor's last update on 25 Sep 2026. 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?
This study is still under way. Results are not available in the source record yet.
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?
Adverse Events (time frame: 50 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Sep 2026.