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NCT Number: NCT07268222

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

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

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Key information

Conditions

Mild Autonomous Cortisol Secretion (MACS)

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Laikon General Hospital

Athens, Greece

Location status: Recruiting

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

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

Other names: osilodrostat, surgery

Osilodrostat 1 MG

Drug

administration of 1-3 mg of osilodrostat at 19.00

Adrenalectomy

Procedure

Surgery performed in patients with MACS

Watch and wait

Other

Follow-up

Primary outcomes

  1. Comparison of the efficacy of metyrapone and osilodrostat

    Time frame: 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

  2. Comparison of the efficacy of metyrapone and osilodristat

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

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

  3. Comparison of the efficacy of metyrapone and osilodristat

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

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

  4. Comparison of the efficacy of metyrapone and osilodristat

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

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

  5. Comparison of metyrapone and osilodrostat efficacy

    Time frame: Baseline (at t=0), at t=3 months , at t =6 months

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

  6. Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters

    Time frame: Baseline (t=0), at t= 3months, at t=6 months

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

Secondary outcomes

  1. Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters

    Time frame: Baseline at t=0 , at 3 months and at 6 months

    Alterations of fasting blood glucose levels (mg/dl) pre and post-treatment

  2. Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters

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

    Alteration of insuline levels (μU/ml) pre and post-treatment

  3. Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters

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

    Alterations of Hb1Ac levels (%) pre and post-treatment

  4. Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters

    Time frame: Baseline (t=0) at t=3 months and t=6 months

    Alterations of HOMA-IR (glucose levels mmol/l x insuline levels mIU/L/22.5) pre and post -treatment

  5. Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters

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

    Alterations of cholesterol levels (mg/dl) pre and post-treatment

  6. Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters

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

    Alterations of triglycerides levels (mg/dl) pre and post-treatment

  7. Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters

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

    Alterations of HDL levels (mg/dl) pre and post-treatment

  8. Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters

    Time frame: Baseline at t=0, at t=3 months , at t=6 months

    Alterations of glucose levels post-OGTT pre and post-treatment

Other outcomes

  1. Comparison of metyrapone and osilodrostat in terms of other parameters

    Time frame: 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

  2. Comparison of metyrapone and osilodrostat in terms of other parameters

    Time frame: Baseline (t=0), t=3 months , t=6 months

    Alterations of BMI (weight (kg) / height(cm2)) levels pre and post-treatment

  3. Comparison of metyrapone and osilodrostat in terms of other parameters

    Time frame: Baseline at t=0 and at t= 1 year

    Alterations of bone mineral density (BMD) in gr /cm3 pre and post-treatment

Study contacts

Contact information is provided by the study sponsor or research team.

Anna Angelousi, MD, PhD, Msc

CONTACT

[email protected]

00306978167876 ext. 0030

Sponsors and collaborators

Lead sponsor

Laikο General Hospital, Athens

Other

Registry information

Acronym: MOMACS

Important dates

Study start
2025
Primary completion
2026
Study completion
2027
First posted
Dec 5, 2025
Registry last updated
Dec 5, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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