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

NCT07268222 | Recruiting Phase 4

• 1 other identifier: Laikon
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Mild Autonomous Cortisol Secretion (MACS)

Keywords

cortisol; Cushing; MACS; METYRAPONE; osilodrostat

Outcome Measures

Primary Outcomes (6)

• Comparison of the efficacy of metyrapone and osilodrostat

  Blood tests measuring baseline moring cortisol (μg/dl) levels pre and post-treatment

  Baseline ( at t=0), at t=3 months and at =6 months

• Comparison of the efficacy of metyrapone and osilodristat

  Measurement of the baseline morning ACTH (pg/ml) pre and post-treatment

  Baseline (at t= 0), at t= 3 months and t= 6 months

• Comparison of the efficacy of metyrapone and osilodristat

  Measurement of the baseline morning DHEAS levels (μg/dl) pre and post-treatment

  Baseline ( at t=0), at t=3 months and at t=6 months

• Comparison of the efficacy of metyrapone and osilodristat

  Measurement of urinary free cortisol (μg/24h) pre and post-treatment

  Baseline ( at t=0), at t=3 months and at =6 months

• Comparison of metyrapone and osilodrostat efficacy

  Measurement of salivary midnight cortisol (μg/dl) pre and post-treatment

  Baseline (at t=0), at t=3 months , at t =6 months

• Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters

  Alteartions of LDL levels (mg/dl) pre and post-treatment

  Baseline (t=0), at t= 3months, at t=6 months

Secondary Outcomes (8)

• Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters

  Baseline at t=0 , at 3 months and at 6 months

• Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters

  Baseline (t=0), at t=3 months and at t=6 months

• Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters

  Baseline (t=0), at t=3 months and at t=6 months

• Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters

  Baseline (t=0) at t=3 months and t=6 months

• Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters

  Baseline (t=0), at t=3 months and at t=6 months

Other Outcomes (3)

• Comparison of metyrapone and osilodrostat in terms of other parameters

  Baseline (t=0), at t=3 months and t=6 months

• Comparison of metyrapone and osilodrostat in terms of other parameters

  Baseline (t=0), t=3 months , t=6 months

• Comparison of metyrapone and osilodrostat in terms of other parameters

  Baseline at t=0 and at t= 1 year

Study Arms (1)

Patients with MACS

OTHER

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.)

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

Interventions

Metyrapone 250 mg Oral Tablets DRUG

metyrapone( 250 -750 mg) vs. osilodrostat (1-3 mg) vs. surgery vs watch and wait strategy in the management of patients with MACS

Also known as: osilodrostat, surgery

Patients with MACS

Osilodrostat 1 MG DRUG

administration of 1-3 mg of osilodrostat at 19.00

Patients with MACS

adrenalectomy PROCEDURE

Surgery performed in patients with MACS

Patients with MACS

Watch and wait OTHER

Follow-up

Patients with MACS

Eligibility Criteria

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

You may qualify if:

• Adults \> 18 years old with MACS and unilateral or bilateral adrenal adenomas or hyperplasia (based on imaging)
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Laikο General Hospital, Athens: lead

Study Sites (1)

Laikon General Hospital

Athens, Greece

RECRUITING

MeSH Terms

Interventions

Metyrapone; Osilodrostat; Surgical Procedures, Operative; Adrenalectomy

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Endocrine Surgical Procedures

Central Study Contacts

Anna Angelousi, MD, PhD, Msc

CONTACT

00306978167876; a.angelousi@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: associate professor

Study Record Dates

• First Submitted: November 21, 2025
• First Posted: December 5, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 25, 2027
• Last Updated: December 5, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)