Mild Autonomous Cortisol Secretion (MACS)Phase 4MOMACSNCT07268222
Metyrapone Versus Osilodrostat in Patients With Metabolic Autonomous Cortisol Secretion (MACS)
A Phase 4 study testing Metyrapone 250 mg Oral Tablets, Osilodrostat 1 MG and adrenalectomy in people with Mild Autonomous Cortisol Secretion (MACS), run by Laikο General Hospital, Athens at 1 site in Greece.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mild Autonomous Cortisol Secretion (MACS)
- What is being tested?
- Metyrapone 250 mg Oral Tablets, Osilodrostat 1 MG and adrenalectomy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteGreece
- Study dates
- 1 Dec 2025to 25 Nov 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
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
- Being tested
- Metyrapone 250 mg Oral Tablets, Osilodrostat 1 MG, adrenalectomy, Watch and wait
- Keywords
- cortisol, Cushing, MACS, METYRAPONE, osilodrostat
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metyrapone 250 mg Oral TabletsDrug
Also called osilodrostat, surgery
metyrapone( 250 -750 mg) vs. osilodrostat (1-3 mg) vs. surgery vs watch and wait strategy in the management of patients with MACS
Osilodrostat 1 MGDrug
administration of 1-3 mg of osilodrostat at 19.00
adrenalectomyProcedure or surgery
Surgery performed in patients with MACS
Watch and waitOther
Follow-up
| Study group | Role | What they receive |
|---|---|---|
| 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.) Receives: Drug: Metyrapone 250 mg Oral Tablets; Drug: Osilodrostat 1 MG; Procedure: adrenalectomy; Other: Watch and wait |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of the efficacy of metyrapone and osilodrostat
Blood tests measuring baseline moring cortisol (μg/dl) levels pre and post-treatment
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Alterations of fasting blood glucose levels (mg/dl) pre and post-treatment
Measured: Baseline at t=0 , at 3 months and at 6 months
Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters
Alteration of insuline levels (μU/ml) pre and post-treatment
Measured: Baseline (t=0), at t=3 months and at t=6 months
Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters
Alterations of Hb1Ac levels (%) pre and post-treatment
Measured: Baseline (t=0), at t=3 months and at t=6 months
Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters
Alterations of HOMA-IR (glucose levels mmol/l x insuline levels mIU/L/22.5) pre and post -treatment
Measured: Baseline (t=0) at t=3 months and t=6 months
Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters
Alterations of cholesterol levels (mg/dl) pre and post-treatment
Measured: Baseline (t=0), at t=3 months and at t=6 months
Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters
Alterations of triglycerides levels (mg/dl) pre and post-treatment
Measured: Baseline (t=0), at t=3 months and at t=6 months
Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters
Alterations of HDL levels (mg/dl) pre and post-treatment
Measured: Baseline (t=0), at t=3 months and at t=6 months
Comparison of metyrapone and osilodrostat in terms of alterations of metabolic parameters
Alterations of glucose levels post-OGTT pre and post-treatment
Measured: Baseline at t=0, at t=3 months , at t=6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2025
- Study start1 Dec 2025
- Primary completion1 Nov 2026 (estimated)
- Study completion25 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mild Autonomous Cortisol Secretion (MACS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Laikο General Hospital, Athens
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anna Angelousi, Laikο General Hospital, Athens
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07268222
- Sponsor's protocol ID
- Laikon
- Acronym
- MOMACS
- Status last verified
- Dec 2025
- First submitted
- 21 Nov 2025
- Last updated
- 5 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metyrapone Versus Osilodrostat in Patients With Metabolic Autonomous Cortisol Secretion (MACS)
- ClinicalTrials.gov ID
- NCT07268222
- Acronym / sponsor ID
- MOMACS / Laikon
- Keywords
- cortisol, Cushing, MACS, METYRAPONE, osilodrostat
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Laikο General Hospital, AthensUniversity, hospital or other
- Study start
- 1 Dec 2025 (actual)
- Primary completion
- 1 Nov 2026 (estimated)
- Study completion
- 25 Nov 2027 (estimated)
- First posted
- 5 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with MACS | Other | Drug: Metyrapone 250 mg Oral Tablets, Drug: Osilodrostat 1 MG, Procedure: adrenalectomy, Other: Watch and waitPatients 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.) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (5 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metyrapone 250 mg Oral TabletsAlso: osilodrostat, surgerymetyrapone( 250 -750 mg) vs. osilodrostat (1-3 mg) vs. surgery vs watch and wait strategy in the management of patients with MACS | Drug | Patients with MACS |
| Osilodrostat 1 MGadministration of 1-3 mg of osilodrostat at 19.00 | Drug | Patients with MACS |
| adrenalectomySurgery performed in patients with MACS | Procedure or surgery | Patients with MACS |
| Watch and waitFollow-up | Other | Patients with MACS |
Primary outcome
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
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
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
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
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
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
8 secondary outcomes
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
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
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
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
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
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
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
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metyrapone 250 mg Oral Tablets, Osilodrostat 1 MG and adrenalectomy in people with Mild Autonomous Cortisol Secretion (MACS), run by Laikο General Hospital, Athens at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anna Angelousi, MD, PhD, Msc (00306978167876 ext. 0030, a.angelousi@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of the efficacy of metyrapone and osilodrostat (time frame: Baseline ( at t=0), at t=3 months and at =6 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2025.