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

Status

Recruiting

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT07268222

Acronym

MOMACS

Enrollment

150

Registered

2025-12-05

Start date

2025-12-01

Completion date

2027-11-25

Last updated

2025-12-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Mild Autonomous Cortisol Secretion (MACS)

Keywords

cortisol, Cushing, MACS, METYRAPONE, osilodrostat

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

Interventions

OTHERWatch and wait

Follow-up

DRUGOsilodrostat 1 MG

administration of 1-3 mg of osilodrostat at 19.00

PROCEDUREadrenalectomy

Surgery performed in patients with MACS

DRUGMetyrapone 250 mg Oral Tablets

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

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

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)

Design outcomes

Primary

Measure	Time frame	Description
Comparison of the efficacy of metyrapone and osilodrostat	Baseline ( at t=0), at t=3 months and at =6 months	Blood tests measuring baseline moring cortisol (μg/dl) levels pre and post-treatment
Comparison of the efficacy of metyrapone and osilodristat	Baseline (at t= 0), at t= 3 months and t= 6 months	Measurement of the baseline morning ACTH (pg/ml) pre and post-treatment
Comparison of metyrapone and osilodrostat efficacy	Baseline (at t=0), at t=3 months , at t =6 months	Measurement of salivary midnight cortisol (μg/dl) pre and post-treatment
Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters	Baseline (t=0), at t= 3months, at t=6 months	Alteartions of LDL levels (mg/dl) pre and post-treatment

Secondary

Measure	Time frame	Description
Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters	Baseline at t=0 , at 3 months and at 6 months	Alterations of fasting blood glucose levels (mg/dl) pre and post-treatment

Other

Measure	Time frame	Description
Comparison of metyrapone and osilodrostat in terms of other parameters	Baseline (t=0), at t=3 months and t=6 months	Alterations of systolic and diastolic blood pressure (mmHg) at morning pre and post-treatment

Countries

Greece

Contacts

Primary ContactAnna Angelousi, MD, PhD, Msc

a.angelousi@gmail.com00306978167876

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026