Metyrapone versus osilodrostat for metabolic autonomous cortisol secretion (MACS)

Metyrapone Versus Osilodrostat in Patients With 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.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Laikο General Hospital, Athens (other)
• Locations: 1 site (Athens)
• Trial ID: NCT07268222 on ClinicalTrials.gov

What this trial studies

Researchers will compare two oral 11β-hydroxylase inhibitors, metyrapone and osilodrostat, in adults with MACS who are managed non-surgically, with follow-up visits at baseline, 3 months, and 6 months to track biochemical and clinical outcomes. The primary outcomes are biochemical cortisol control and clinical side effects at 0, 3, and 6 months, while secondary outcomes include blood pressure, BMI, fasting glucose/insulin measures, lipids, and a one-year bone mineral density assessment. Eligible participants must meet biochemical criteria on overnight dexamethasone suppression testing and have adrenal adenomas or hyperplasia on imaging; key exclusions include abnormal liver tests, eGFR <40, ACTH-dependent Cushing, and active or prior malignancy. Treatments include oral metyrapone or osilodrostat, with surgical adrenalectomy or observational management considered when appropriate, and all visits occur at Laikon General Hospital in Athens.

Who should consider this trial

Good fit: Adults over 18 with MACS due to unilateral or bilateral adrenal adenomas or hyperplasia who meet the dexamethasone suppression and cortisol/ACTH criteria and are being managed non-surgically.

Not a fit: People with ACTH-dependent Cushing's, suspected or past adrenal malignancy, abnormal liver enzymes, significant kidney impairment, or those planning immediate adrenalectomy are unlikely to benefit from this medical comparison.

Why it matters

Potential benefit: If one drug is more effective or safer, patients with MACS could achieve better cortisol control and improvements in blood pressure, weight, metabolic measures, and bone health without needing surgery.

How similar studies have performed: Both metyrapone and osilodrostat are established cortisol-lowering drugs with positive results in Cushing's disease or hypercortisolism, but direct head-to-head comparisons in MACS are limited, making this specific comparison relatively novel.

Eligibility criteria

Inclusion Criteria:

* Adults \> 18 years old with MACS and unilateral or bilateral adrenal adenomas or hyperplasia (based on imaging)
* 1 mg overnight dexamethasone suppression test (ODST): Cortisol levels at 8.00 am\>1.8 μg/dl AND i) ACTH\< 15 pg/ml OR ii) abnormal midnight salivary cortisol OR iii) Urinary free cortisol levels (UFC) /24h ≥ of the UNL

Exclusion Criteria:

* Abnormal liver enzymes
* eGFR \< 40 ml/min/1.73 m3
* Pseudocushing syndrome
* Patients with any malignancy (active or past history), including ACC
* ACTH-dependent Cushing syndrome (Cushing disease or ectopic Cushing syndrome)

Where this trial is running

Athens

• Laikon General Hospital — Athens, Greece (RECRUITING)

Study contacts

• Study coordinator: Anna Angelousi, MD, PhD, Msc

Conditions: Mild Autonomous Cortisol Secretion, cortisol, Cushing, MACS, METYRAPONE, osilodrostat