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Active, not recruitingNCT06106295Updated Sep 25, 2026

Metyrapone for Mild Autonomous Cortisol Secretion (MACS)

A Phase 2 interventional study of Metyrapone in Autonomous Cortisol Secretion and Mild Autonomous Cortisol Secretion (MACS), sponsored by Mayo Clinic. Active, not recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-25.

Sponsored by Mayo Clinic · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
30
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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 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.

02

Conditions studied

  • Autonomous Cortisol Secretion
  • Mild Autonomous Cortisol Secretion (MACS)

Keywords

  • Hypercortisolism
  • Cortisol excess
  • Cushing syndrome
  • Adrenal adenoma
  • Adrenal hyperplasia
03

In context

Cushing Syndrome

123 studies on the registry are indexed under Cushing Syndrome; 37 are open to participants now.

This study's planned enrollment of 30 is below the median of 50 across 59 interventional studies indexed under Cushing Syndrome.

Browse Cushing Syndrome studies →

Lead sponsor

Mayo Clinic is the lead sponsor of 3,218 studies on the registry; 670 are open to participants now.

Of its 445 completed or terminated interventional studies of FDA-regulated products, 313 (70%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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.
  • 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

Exclusion criteria

Exclusion Criteria:

  • 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.
  • 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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
30 participants (estimated)

Study arms

  • Experimental
    Mild Autonomous Cortisol Secretion (MACS) Open Label Phase and Optional Extension Phase

    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.

    Drug: Metyrapone

Interventions

  • DrugMetyrapone

    250 to 1000 milligram (mg) orally in one or two doses in the evening (administered 4 and 2 hours prior to bed)

06

What researchers measure

Primary outcomes

  1. Adverse Events

    Number of participants to experience adverse events

    Time frame: 50 months

07

Study locations

1 site
  • Mayo Clinic Minnesota
    Rochester, Minnesota 55905, United States
08

References and documents

Individual participant data

Plan to share: No

09

Updates

1 registry update since Sep 25, 2026
Minor edits
Nothing that changes what the study is or who can join. Edited: verification date
1 update, last Sep 25, 2026
Show all 1 update
  1. Sep 25, 2026
    Minor edits only
    + 1 other change: verification date

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT06106295
Lead sponsor
Mayo Clinic
Responsible party
Irina Bancos (Principal Investigator, Mayo Clinic) — Principal investigator
First posted
Oct 30, 2023
Start date
Dec 19, 2023
Primary completion
Jan 31, 2028 (estimated)
Completion
Feb 1, 2028 (estimated)
Last update
Sep 25, 2026

Study contacts

Irina Bancos, MD
principal investigator · Mayo Clinic

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.

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