Mild Autonomous Cortisol Secretion (MACS)Phase 2GLYCOSIL-MACSNCT07922148
Osilodrostat for Glycemic Control in Mild Autonomous Cortisol Secretion (MACS) With Difficult-To-Control Type 2 Diabetes - A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study
A Phase 2 study testing Osilodrostat (Isturisa) and hydrocortisone 10mg in people with Mild Autonomous Cortisol Secretion (MACS) and Diabetes Mellitus (Type 2), run by Beckey Trinh at 1 site in Switzerland.
Trial summary
This single-centre, randomized, double-blind, placebo-controlled phase 2 trial investigates whether lowering cortisol with osilodrostat improves blood-glucose control in adults with mild autonomous cortisol secretion (MACS) and difficult-to-control type 2 diabetes. Read more about this study
- Who is it for?
- Ages 18 to 74 years
- Conditions the study is for
- Mild Autonomous Cortisol Secretion (MACS), Diabetes Mellitus (Type 2)
- What is being tested?
- Osilodrostat (Isturisa) and hydrocortisone 10mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteSwitzerland
- Study dates
- Nov 2026to Oct 2029
- Phase
- Phase 2
- 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 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 to <75 years.
- Confirmed MACS per ESE 2023 guidelines: serum cortisol >50 nmol/L after 1 mg dexamethasone suppression test, low ACTH and DHEAS, and uni-/bilateral adrenal adenoma(s) or macronodular/micronodular/diffuse bilateral adrenal hyperplasia on CT or MRI.
- Morning serum cortisol >300 nmol/L.
- Difficult-to-control type 2 diabetes: HbA1c >7.0% despite one of - ≥3 glucose-lowering medications; insulin plus ≥1 glucose-lowering medication; ≥2 glucose-lowering medications and ≥1 micro-/macrovascular complication; or ≥2 glucose-lowering and ≥2 blood-pressure-lowering medications.
- Stable background pharmacotherapy for ≥4 weeks before the first study visit.
- For persons of childbearing potential: agreement to abstinence or contraception with a failure rate ≤1%/year during treatment and for 1 month after the last dose.
Who cannot join
- Age ≥75 years (osilodrostat not sufficiently studied in this age group per the SmPC).
- Known hypersensitivity to osilodrostat, its excipients, or the placebo.
- Planned adrenalectomy before completion of the study.
- Malignant adrenal tumour.
- Type 1 diabetes; new-onset diabetes (<1 year).
- Systemic glucocorticoid therapy within 3 months, or planned use.
Show all 20Show fewer
- Current/recent intake of medications affecting adrenal steroidogenesis or cortisol assessment.
- Concomitant therapy with clinically relevant drug-drug interactions with osilodrostat (strong CYP3A4 inhibitors; strong CYP3A4/CYP2B6 inducers; QT-prolonging medicinal products).
- Participation in another interventional trial within the last 30 days.
- Pregnancy or breastfeeding; WOCBP unwilling to use highly effective contraception.
- Excessive alcohol consumption; severe untreated sleep apnea; night-shift work.
- Severe psychiatric, medical or surgical illness.
- Severe renal impairment (eGFR < 30 mL/min/1.73 m²), hemodialysis or end-stage renal disease.
- Liver cirrhosis Child-Pugh B or C.
- Refractory hypokalemia or hypomagnesemia (not correctable to K ≥4.0 and Mg ≥1.0 mmol/L before first dose).
- QTc > 480 ms on baseline ECG, or known congenital long QT syndrome.
- Uncontrolled arterial hypertension (≥ 160/100 mmHg despite therapy)
- Uncontrolled thyroid disease
- Severe cardiovascular disease (NYHA class III-IV heart failure, myocardial infarction or unstable angina within the previous 6 months, or clinically significant arrhythmia)
- History of breast or endometrial carcinoma
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site
University Hospital Basel, Clinic of Endocrinology, Diabetology & Metabolism
Basel
Beckey Trinh, PD, MD, PhD, +41612655078, beckey.trinh@usb.ch
About this study
This single-centre, randomized, double-blind, placebo-controlled phase 2 trial investigates whether lowering cortisol with osilodrostat improves blood-glucose control in adults with mild autonomous cortisol secretion (MACS) and difficult-to-control type 2 diabetes. Forty-four participants are randomly assigned 1:1 to osilodrostat or matching placebo, taken once daily for 12 weeks, together with a blinded hydrocortisone/placebo for stress (sick-day) dosing. The primary outcome is the change in HbA1c from baseline to week 12; secondary outcomes include continuous glucose monitoring (CGM) metrics, cardiometabolic parameters, cortisol measures and quality of life. Participants are followed for a safety visit 4 weeks after the end of treatment.
Read the detailed description
MACS is a common, mild form of endogenous hypercortisolism that may adversely affect glucose metabolism. In participants with confirmed MACS and difficult-to-control type 2 diabetes, this trial tests whether pharmacological cortisol reduction with osilodrostat improves glycaemic control. After a screening visit and a 14-day CGM run-in, participants are randomized 1:1 to osilodrostat 1 mg once daily at 18:00 (single optional escalation to 2 mg after 14 days, safety-guided) or matching placebo for 12 weeks; both arms receive a blinded hydrocortisone/placebo for stress dosing (double-dummy). Background glucose- and blood-pressure-lowering therapy is continued and adjusted only per predefined safety algorithms. Assessments include HbA1c, continuous glucose monitoring, blood pressure, lipids, anthropometrics, DXA body composition and bone density, plasma/salivary/urinary cortisol, quality-of-life and sleep questionnaires, and safety laboratory and ECG monitoring. The primary analysis is an ANCOVA of the change in HbA1c at week 12 in the intention-to-treat population under a treatment-policy estimand; CGM endpoints are analysed with mixed-effects models for repeated measures.
- Being tested
- Osilodrostat (Isturisa), Placebo, hydrocortisone 10mg, Placebo (for hydrocortisone)
- Keywords
- osilodrostat, cortisol, hypercortisolism, MACS, CGMS, HbA1c, glycemic control
- Medical subject headings
- Diabetes Mellitus, Type 2, Cushing Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Osilodrostat (Isturisa)Drug
1 mg film-coated tablet, orally once daily at 18:00; optional single escalation to 2 mg after 14 days; 12 weeks.
PlaceboDrug
placebo tablet, orally once daily at 18:00; 12 weeks
hydrocortisone 10mgDrug
blinded stress/sick-day (rescue) dosing only, per written instructions
Placebo (for hydrocortisone)Drug
placebo tablet for stress-dosing regimen
| Study group | Role | What they receive |
|---|---|---|
| Osilodrostat | Experimental | Osilodrostat 1 mg once daily at 18:00 for 12 weeks (single optional escalation to 2 mg after 14 days), plus blinded hydrocortisone 10 mg for stress/sick-day dosing only. Receives: Drug: Osilodrostat (Isturisa); Drug: hydrocortisone 10mg |
| Placebo | Placebo comparator | Placebo once daily at 18:00 for 12 weeks, plus blinded placebo for hydrocortisone (identical schedule). Receives: Drug: Placebo; Drug: Placebo (for hydrocortisone) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in HbA1c at week 12
Between-group difference in HbA1c change (%). Time Frame: Baseline and week 12
Measured: Baseline and week 12
Secondary outcomes (16)
CGM Time in Range (3.9-10.0 mmol/L, %)
14-day windows preceding baseline, week 6 and week 12.
Measured: baseline, week 6 and week 12
CGM Time in Tight Range (3.9-7.8 mmol/L, %)
14-day windows preceding baseline, week 6 and week 12.
Measured: baseline, week 6 and week 12
CGM Time below range (<3.9 and <3.0 mmol/L, %)
14-day windows preceding baseline, week 6 and week 12
Measured: baseline, week 6 and week 12
CGM Time above range (>10.0 and >13.9 mmol/L, %)
14-day windows preceding baseline, week 6 and week 12.
Measured: baseline, week 6 and week 12
Change in blood pressure
Measured: Baseline and week 12
Change in lipid profile
Measured: Baseline and week 12
Change in body weight and waist/hip circumference
Measured: Baseline and week 12
Change in DXA-derived body composition
Measured: Baseline and week 12
Proportion of participants requiring reduction of hypoglycemia-causing therapy (insulin/sulfonylurea)
Measured: Baseline to week 12
Change in antihypertensive medication
Measured: Baseline to week 12
Change in plasma cortisol
Measured: Baseline and week 12
Change in salivary cortisol
Measured: Baseline to week 12
Change in 24-h urinary cortisol
Measured: Baseline and week 12
Change from baseline in health-related quality of life (SF-36)
8 subscales + physical/mental component summaries, 0-100, higher = better
Measured: Baseline and week 12
Change from baseline in disease-specific quality of life (CushingQoL questionnaire)
higher = better
Measured: Baseline and week 12
Change from baseline in sleep quality (Pittsburgh Sleep Quality Index, PSQI)
global score 0-21, higher = worse sleep
Measured: Baseline and week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2026
- Study startNov 2026 (estimated)
- Primary completionApr 2029 (estimated)
- Study completionOct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beckey Trinh
- Sponsor type
- University, hospital or other
- Collaborators
- Bangerter-Rhyner Foundation, RECORDATI GROUP
- Responsible party
- Sponsor-investigator, Beckey Trinh, University Hospital, Basel, Switzerland
- Investigators
- Beckey Trinh, PD, MD, PhD, Principal investigator, University Hospital, Basel, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07922148
- Sponsor's protocol ID
- GLYCOSIL-MACS
- Other IDs
- 2026-01499, 205.123670, SNCTP000007077
- Acronym
- GLYCOSIL-MACS
- Status last verified
- Nov 2026
- First submitted
- 23 Sep 2026
- Last updated
- 6 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Coded study data are held by the sponsor in Switzerland; only anonymised/aggregated data and the final report are shared externally, per the protocol data-protection section.
Publications
Fassnacht M, Tsagarakis S, Terzolo M, Tabarin A, Sahdev A, Newell-Price J, Pelsma I, Marina L, Lorenz K, Bancos I, Arlt W, Dekkers OM. European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2023 Jul 20;189(1):G1-G42. doi: 10.1093/ejendo/lvad066.
PubMed 37318239
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Osilodrostat for Glycemic Control in Mild Autonomous Cortisol Secretion (MACS) With Difficult-To-Control Type 2 Diabetes - A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study
- ClinicalTrials.gov ID
- NCT07922148
- Acronym / sponsor ID
- GLYCOSIL-MACS / GLYCOSIL-MACS
- Keywords
- osilodrostat, cortisol, hypercortisolism, MACS, CGMS, HbA1c, glycemic control
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- Beckey TrinhUniversity, hospital or other
- Collaborators
- Bangerter-Rhyner Foundation, RECORDATI GROUP
- Study start
- Nov 2026 (estimated)
- Primary completion
- Apr 2029 (estimated)
- Study completion
- Oct 2029 (estimated)
- First posted
- 6 Nov 2026 (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 single-centre, randomized, double-blind, placebo-controlled phase 2 trial investigates whether lowering cortisol with osilodrostat improves blood-glucose control in adults with mild autonomous cortisol secretion (MACS) and difficult-to-control type 2 diabetes. Forty-four participants are randomly assigned 1:1 to osilodrostat or matching placebo, taken once daily for 12 weeks, together with a blinded hydrocortisone/placebo for stress (sick-day) dosing. The primary outcome is the change in HbA1c from baseline to week 12; secondary outcomes include continuous glucose monitoring (CGM) metrics, cardiometabolic parameters, cortisol measures and quality of life. Participants are followed for a safety visit 4 weeks after the end of treatment.
Detailed description
MACS is a common, mild form of endogenous hypercortisolism that may adversely affect glucose metabolism. In participants with confirmed MACS and difficult-to-control type 2 diabetes, this trial tests whether pharmacological cortisol reduction with osilodrostat improves glycaemic control. After a screening visit and a 14-day CGM run-in, participants are randomized 1:1 to osilodrostat 1 mg once daily at 18:00 (single optional escalation to 2 mg after 14 days, safety-guided) or matching placebo for 12 weeks; both arms receive a blinded hydrocortisone/placebo for stress dosing (double-dummy). Background glucose- and blood-pressure-lowering therapy is continued and adjusted only per predefined safety algorithms. Assessments include HbA1c, continuous glucose monitoring, blood pressure, lipids, anthropometrics, DXA body composition and bone density, plasma/salivary/urinary cortisol, quality-of-life and sleep questionnaires, and safety laboratory and ECG monitoring. The primary analysis is an ANCOVA of the change in HbA1c at week 12 in the intention-to-treat population under a treatment-policy estimand; CGM endpoints are analysed with mixed-effects models for repeated measures.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Osilodrostat | Experimental | Drug: Osilodrostat (Isturisa), Drug: hydrocortisone 10mgOsilodrostat 1 mg once daily at 18:00 for 12 weeks (single optional escalation to 2 mg after 14 days), plus blinded hydrocortisone 10 mg for stress/sick-day dosing only. |
| Placebo | Placebo comparator | Drug: Placebo, Drug: Placebo (for hydrocortisone)Placebo once daily at 18:00 for 12 weeks, plus blinded placebo for hydrocortisone (identical schedule). |
Who may qualify
- Ages
- 18 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age 18 to <75 years.
- Confirmed MACS per ESE 2023 guidelines: serum cortisol >50 nmol/L after 1 mg dexamethasone suppression test, low ACTH and DHEAS, and uni-/bilateral adrenal adenoma(s) or macronodular/micronodular/diffuse bilateral adrenal hyperplasia on CT or MRI.
- Morning serum cortisol >300 nmol/L.
- Difficult-to-control type 2 diabetes: HbA1c >7.0% despite one of - ≥3 glucose-lowering medications; insulin plus ≥1 glucose-lowering medication; ≥2 glucose-lowering medications and ≥1 micro-/macrovascular complication; or ≥2 glucose-lowering and ≥2 blood-pressure-lowering medications.
- Stable background pharmacotherapy for ≥4 weeks before the first study visit.
Key exclusion criteria (20 listed)
- Age ≥75 years (osilodrostat not sufficiently studied in this age group per the SmPC).
- Known hypersensitivity to osilodrostat, its excipients, or the placebo.
- Planned adrenalectomy before completion of the study.
- Malignant adrenal tumour.
- Type 1 diabetes; new-onset diabetes (<1 year).
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 |
|---|---|---|
| Osilodrostat (Isturisa)1 mg film-coated tablet, orally once daily at 18:00; optional single escalation to 2 mg after 14 days; 12 weeks. | Drug | Osilodrostat |
| Placeboplacebo tablet, orally once daily at 18:00; 12 weeks | Drug | Placebo |
| hydrocortisone 10mgblinded stress/sick-day (rescue) dosing only, per written instructions | Drug | Osilodrostat |
| Placebo (for hydrocortisone)placebo tablet for stress-dosing regimen | Drug | Placebo |
Primary outcome
Change from baseline in HbA1c at week 12
Time frame: Baseline and week 12
Between-group difference in HbA1c change (%). Time Frame: Baseline and week 12
16 secondary outcomes
CGM Time in Range (3.9-10.0 mmol/L, %)
Time frame: baseline, week 6 and week 12
CGM Time in Tight Range (3.9-7.8 mmol/L, %)
Time frame: baseline, week 6 and week 12
CGM Time below range (<3.9 and <3.0 mmol/L, %)
Time frame: baseline, week 6 and week 12
CGM Time above range (>10.0 and >13.9 mmol/L, %)
Time frame: baseline, week 6 and week 12
Change in blood pressure
Time frame: Baseline and week 12
Change in lipid profile
Time frame: Baseline and week 12
Change in body weight and waist/hip circumference
Time frame: Baseline and week 12
Change in DXA-derived body composition
Time frame: Baseline and week 12
Proportion of participants requiring reduction of hypoglycemia-causing therapy (insulin/sulfonylurea)
Time frame: Baseline to week 12
Change in antihypertensive medication
Time frame: Baseline to week 12
Change in plasma cortisol
Time frame: Baseline and week 12
Change in salivary cortisol
Time frame: Baseline to week 12
Change in 24-h urinary cortisol
Time frame: Baseline and week 12
Change from baseline in health-related quality of life (SF-36)
Time frame: Baseline and week 12
Change from baseline in disease-specific quality of life (CushingQoL questionnaire)
Time frame: Baseline and week 12
Change from baseline in sleep quality (Pittsburgh Sleep Quality Index, PSQI)
Time frame: Baseline and week 12
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 6 Nov 2026.
- Background: PubMed 37318239Fassnacht M, Tsagarakis S, Terzolo M, Tabarin A, Sahdev A, Newell-Price J, Pelsma I, Marina L, Lorenz K, Bancos I, Arlt W, Dekkers OM. European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2023 Jul 20;189(1):G1-G42. doi: 10.1093/ejendo/lvad066.
- Individual participant dataSharing planned: No. Coded study data are held by the sponsor in Switzerland; only anonymised/aggregated data and the final report are shared externally, per the protocol data-protection section.
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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.
Beckey Trinh, PD, MD, PhD principal investigator
University Hospital, Basel, Switzerland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Osilodrostat (Isturisa) and hydrocortisone 10mg in people with Mild Autonomous Cortisol Secretion (MACS) and Diabetes Mellitus (Type 2), run by Beckey Trinh at 1 site in Switzerland.
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 6 inclusion and 20 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: opening soon, as of the sponsor's last update on 6 Nov 2026. 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 Switzerland. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Beckey Trinh, PD, MD, PhD (+41612655078, beckey.trinh@usb.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in HbA1c at week 12 (time frame: Baseline and week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07922148, which also lists 1 linked publication.
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 6 Nov 2026.