Metyrapone Study for Patients Diagnosed With Mild Autonomous Cortisol Secretion - MACS

NCT ID: NCT07138274

Last Updated: 2025-08-22

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-04-30
• Study Completion Date: 2031-12-31

Brief Summary

single-center, randomized, double-blind, placebo-controlled Phase 2 study to evaluate safety and efficacy of overnight metyrapone in patients with MACS.

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.

Conditions

Mild Autonomous Cortisol Secretion (MACS); Autonomous Cortisol Secretion (ACS)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Metyrapone

Subjects in the Metyrapone arm will receive the study drug

Group Type: EXPERIMENTAL

Metyrapone 250 mg Oral Tablets

Intervention Type: DRUG

Subjects will receive metyrapone beginning at 500 mg and titrating up to 1000 mg

Placebo

Subjects in the placebo arm will receive a placebo in lieu of study drug

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Subjects will receive placebo at 500 mg dose and titrated up to 1000 mg to match interventional arm and prevent unblinding

Interventions

Metyrapone 250 mg Oral Tablets

Subjects will receive metyrapone beginning at 500 mg and titrating up to 1000 mg

Intervention Type: DRUG

Placebo

Subjects will receive placebo at 500 mg dose and titrated up to 1000 mg to match interventional arm and prevent unblinding

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Irina Bancos

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Irina Bancos, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Central Contacts

Vanessa Fell, MA

Role: CONTACT

fell.vanessa@mayo.edu

507-266-6068

Other Identifiers

25-007821

Identifier Type: -

Identifier Source: org_study_id