Metyrapone Versus Osilodrostat in Patients With Metabolic Autonomous Cortisol Secretion (MACS) (MOMACS)

Laikο General Hospital, Athens

Status and phase: Enrolling; Phase 4

Conditions: Mild Autonomous Cortisol Secretion (MACS)

Treatments: Drug: Metyrapone 250 mg Oral Tablets; Other: Watch and wait; Procedure: adrenalectomy; Drug: Osilodrostat 1 MG

Study type: Interventional

Funder types: Other

Identifiers

NCT07268222

Laikon

Details and patient eligibility

About

This study will compare the efficacy and safety of the two 11β-hydroxylase inhibitors-metyrapone and osilodrostat-in patients with MACS.

Primary outcome To compare the efficacy (biochemical and clinical) of the two 11β-hydroxylase inhibitors (CYP11B1), metyrapone and osilodrostat, in patients with MACS not treated surgically (mainly bilateral adenomas or adrenal hyperplasias), as well as their side effects at time 0-, 3- and 6-months post-treatment.

Secondary outcome To evaluate alterations in clinical parameters (Blood Pressure, Body Mass Index-BMI), metabolic parameters (fasting blood glucose, insulin, Hb1Ac, HOMA, OGTT and lipids levels) at time 0-, 3- and 6-month after the initiation of the treatment and their effect on Bone Mineral Density (BMD) 1 year post-diagnosis

Enrollment: 150 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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150 participants in 1 patient group

Patients with MACS

Other group

Description:

Patients with MACS (Adults \> 18 years old with 1mg ODST F levels \>1.8μg/dl and normal or slightly abnormal UFC OR midnight salivary cortisol levels AND no symptoms or signs of overt hypercortisolism.)

Treatment:

Procedure: adrenalectomy

Drug: Osilodrostat 1 MG

Other: Watch and wait

Drug: Metyrapone 250 mg Oral Tablets