Metyrapone for Mild Autonomous Cortisol Secretion (MACS)

NCT06106295 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 23-008085
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Autonomous Cortisol Secretion; Mild Autonomous Cortisol Secretion (MACS)

Keywords

Hypercortisolism; Cortisol excess; Cushing syndrome; Adrenal adenoma; Adrenal hyperplasia

Outcome Measures

Primary Outcomes (1)

• Adverse Events

  Number of participants to experience adverse events

  50 months

Study Arms (1)

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.

Drug: Metyrapone

Interventions

Metyrapone DRUG

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

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic Minnesota

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Cushing Syndrome; ACTH Syndrome, Ectopic; Adrenal Hyperplasia, Congenital

Interventions

Metyrapone

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases; Paraneoplastic Endocrine Syndromes; Paraneoplastic Syndromes; Neoplasms; Adrenogenital Syndrome; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Steroid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Irina Bancos, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 24, 2023
• First Posted: October 30, 2023
• Study Start: December 19, 2023
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)