Metyrapone for Mild Autonomous Cortisol Secretion

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a randomized, double-blind, placebo-controlled Phase 2 trial at a single center evaluating the safety and effectiveness of overnight metyrapone in adults with Mild Autonomous Cortisol Secretion. Participants are randomized in a 2:1 ratio to receive metyrapone or placebo for six months, with an option after six months to switch to open-label metyrapone or observe for another six months. Remote screening and consent streamline enrollment, and eligibility includes typical MACS criteria, imaging consistent with benign adrenal disease, and at least one metabolic or skeletal comorbidity. The primary aim is to see if metyrapone can meaningfully reduce cortisol excess while maintaining an acceptable safety profile.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Provide written informed consent.
2. Stated willingness to comply with all study procedures and availability for the duration of the study.
3. Age ≥ 18 years
4. 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.
5. Adrenal imaging phenotype consistent with benign disease (adrenal adenoma/s, macronodular or micronodular adrenal hyperplasia)
6. At least one of the following comorbidities:

   1. obesity (BMI\>30 kg/m2)
   2. dysglycemia
   3. dyslipidemia
   4. hypertension
   5. osteopenia
   6. osteoporosis
   7. fragility fractures
7. Ability to take oral medication and be willing to adhere to the study intervention regimen.
8. 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.
9. Stable timing for bedtime for at least one week prior to on-site study visits.
10. History of difficulty providing blood via standard blood draw methods

Exclusion Criteria:

1. Planned alternative therapy for MACS within 12 months after joining the study.
2. Current use of oral exogenous glucocorticoid therapy
3. Current use of opioid therapy \>20 MME/day
4. Planned use of oral exogenous glucocorticoid therapy
5. Planned use of opioid therapy \>20 MME/day
6. Use of injectable glucocorticoid within 6 weeks prior to Day 1
7. Investigator's judgement based on history/physical examination that a comorbidity or concomitant medication may impact the hypothalamic-pituitary-adrenal axis or steroid metabolome
8. 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
9. Pregnancy or lactation
10. Known allergic reactions to metyrapone
11. Suspected false positive post-dexamethasone cortisol results due to increased metabolism, poor absorption, or noncompliance with dexamethasone
12. Treatment with another investigational drug or other intervention within lower than specific therapy washout period

Where it's running

• Mayo Clinic
  Rochester, Minnesota, United States Recruiting

Study contacts

• Principal investigator: Irina Bancos, MD, MS — Mayo Clinic
• Study coordinator: Vanessa Fell, MA
• Email: fell.vanessa@mayo.edu
• Phone: 507-266-6068

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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• Tirzepatide after adrenalectomy for MACS

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• Metyrapone versus osilodrostat for metabolic autonomous cortisol secretion (MACS)

  This trial will test whether metyrapone or osilodrostat better lowers cortisol and improves health in adults with mild autonomous cortisol secretion (MACS) who are not having surgery.

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• Low-dose (1 mg) osilodrostat for mild autonomous cortisol secretion

  This trial will test whether taking 1 mg of osilodrostat daily is safe and can lower cortisol measures in adults with mild autonomous cortisol secretion.

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.