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

NCT07138274 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 25-007821
• Study Type: interventional
• Target: 90
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Glucocorticoid to androgen ratio

  Glucocorticoid to androgen ratio will be calculated based on total glucocorticoids and total androgens measured through 25-steroid urine profiling.

  3 and 6 months

• Delta salivary cortisone

  Waking salivary cortisone and bedtime salivary cortisone will be assessed, and delta calculated.

  3 and 6 months

Secondary Outcomes (7)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  0-6 months

• Change in body mass index (BMI)

  3 and 6 months

• Adrenal insufficiency symptoms as assessed by the AddiQoL Survey

  Baseline, 1 week post dose titration, 3 and 6 months

• Adrenal insufficiency as assessed through morning ACTH and cortisol measurements.

  baseline, 3, 6 months

• Improvement in hyperglycemia

  3 and 6 months

Study Arms (2)

Metyrapone

EXPERIMENTAL

Subjects in the Metyrapone arm will receive the study drug

Drug: Metyrapone 250 mg Oral Tablets

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Metyrapone 250 mg Oral Tablets DRUG

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

Metyrapone

Placebo DRUG

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

Placebo

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.
• 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:
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Mayo Clinic: lead

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, MS

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vanessa Fell, MA

CONTACT

507-266-6068; fell.vanessa@mayo.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 24, 2025
• First Posted: August 22, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): December 1, 2031
• Last Updated: August 22, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share