Mild Autonomous Cortisol Secretion (MACS)Phase 2NCT07138274
Metyrapone Study for Patients Diagnosed With Mild Autonomous Cortisol Secretion - MACS
A Phase 2 study testing Metyrapone 250 mg Oral Tablets in people with Mild Autonomous Cortisol Secretion (MACS) and Autonomous Cortisol Secretion (ACS), run by Mayo Clinic at 1 site in United States.
Trial summary
single-center, randomized, double-blind, placebo-controlled Phase 2 study to evaluate safety and efficacy of overnight metyrapone in patients with MACS. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mild Autonomous Cortisol Secretion (MACS), Autonomous Cortisol Secretion (ACS)
- What is being tested?
- Metyrapone 250 mg Oral Tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2026to Dec 2031
- Phase
- Phase 2
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.
- Age ≥ 18 years
- Diagnosed with MACS i. at least 2 abnormal post-dexamethasone cortisol results1 mg post-dexamethasone cortisol >1.8 mcg/dL or ii. 8 mg post-dexamethasone cortisol >1 mcg/dL b. 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:
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- obesity (BMI>30 kg/m2)
- dysglycemia
- dyslipidemia
- hypertension
- osteopenia
- osteoporosis
- fragility fractures
- Ability to take oral medication and be willing to adhere to the study intervention regimen.
- 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 1 month after the last dose of study treatment.
- Stable timing for bedtime for at least one week prior to on-site study visits.
- History of difficulty providing blood via standard blood draw methods
Who cannot join
- Planned alternative therapy for MACS within 12 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 6 weeks prior to Day 1
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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. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Mayo Clinic
Rochester, Minnesota, 55905
Vanessa Fell, MA, 507-266-6068, fell.vanessa@mayo.edu
Irina Bancos, MD, MS
About this study
Official title: A Phase II, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Metyrapone in Subjects Diagnosed With Mild Autonomous Cortisol Secretion (MACS)
single-center, randomized, double-blind, placebo-controlled Phase 2 study to evaluate safety and efficacy of overnight metyrapone in patients with MACS.
Read the detailed description
This study is a double blind, placebo-controlled phase II trial of the safety and efficacy of Metyrapone, in the treatment of MACS. Subjects will be remotely screened and interested qualified subjects will be remotely consented. Subjects will be randomized 2:1 for 6 months of the main study. At 6 months, two options will be available for subjects for months 6-12: open-label arm, observational arm.
- Being tested
- Metyrapone 250 mg Oral Tablets, Placebo
- 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.
Metyrapone 250 mg Oral TabletsDrug
Subjects will receive metyrapone beginning at 500 mg and titrating up to 1000 mg
PlaceboDrug
Subjects will receive placebo at 500 mg dose and titrated up to 1000 mg to match interventional arm and prevent unblinding
| Study group | Role | What they receive |
|---|---|---|
| Metyrapone | Experimental | Subjects in the Metyrapone arm will receive the study drug Receives: Drug: Metyrapone 250 mg Oral Tablets |
| Placebo | Placebo comparator | Subjects in the placebo arm will receive a placebo in lieu of study drug Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glucocorticoid to androgen ratio
Glucocorticoid to androgen ratio will be calculated based on total glucocorticoids and total androgens measured through 25-steroid urine profiling.
Measured: 3 and 6 months
Delta salivary cortisone
Waking salivary cortisone and bedtime salivary cortisone will be assessed, and delta calculated.
Measured: 3 and 6 months
Secondary outcomes (7)
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
The investigators will assess adverse events using CTCAE v4.0 at baseline and continuously.
Measured: 0-6 months
Change in body mass index (BMI)
The investigators will assess for change in the body mass index with metyrapone therapy.
Measured: 3 and 6 months
Adrenal insufficiency symptoms as assessed by the AddiQoL Survey
The investigators will administer AddiQoL Survey at baseline, 1 week after each dose titration, and at 3 and 6 months.
Measured: Baseline, 1 week post dose titration, 3 and 6 months
Adrenal insufficiency as assessed through morning ACTH and cortisol measurements.
The investigators will measure ACTH and cortisol in the morning at baseline, 3 and 6 months to assess for biochemical adrenal insufficiency.
Measured: baseline, 3, 6 months
Improvement in hyperglycemia
The investigators will assess for improvement in hyperglycemia by using a composite assessment defined as: 1) decrease in fasting glucose of Hb1C, or 2) Stable biochemical measurements with a decrease in intensity of hyperglycemia therapy
Measured: 3 and 6 months
Improvement in hypertension
The investigators will assess for improvement in hypertension using a composite assessment: 1) improvement in blood pressure measurements while on stable therapy, or 2) stable blood pressure measurements while on a lower intensity hypertension therapy.
Measured: 3 and 6 months
Quality of life as assessed by SF36 form
The investigators will assess quality of life using SF36 at baseline, 3 and 6 months.
Measured: 3 and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2025
- Study startOct 2026 (estimated)
- Primary completionJun 2031 (estimated)
- Study completionDec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mild Autonomous Cortisol Secretion (MACS)Studies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 90 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, MS, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07138274
- Sponsor's protocol ID
- 25-007821
- Status last verified
- Sep 2026
- First submitted
- 24 Jul 2025
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes