Low-dose (1 mg) osilodrostat for mild autonomous cortisol secretion
Impact of 1 mg Osilodrostat Therapy on Mild Autonomous Cortisol Secretion (MACS)
This trial will test whether taking 1 mg of osilodrostat daily is safe and can lower cortisol measures in adults with mild autonomous cortisol secretion.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 15 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Mayo Clinic Academic / other |
| Locations | 1 site (Rochester, Minnesota) |
| Trial ID | NCT07104812 on ClinicalTrials.gov |
What this trial studies
This is a Phase 2 interventional trial in which adults with mild autonomous cortisol secretion will receive daily oral osilodrostat 1 mg with close safety monitoring. Investigators will measure changes in the 24-hour urine steroid metabolome and circadian cortisol and cortisone concentrations using serial urine and blood samples. Eligible participants must have confirmed MACS by abnormal dexamethasone suppression testing and adrenal imaging consistent with benign adenoma or hyperplasia, plus at least one metabolic or bone-related comorbidity. Safety, tolerability, and biochemical hormone changes are the primary focus of the protocol.
Who should consider this trial
Good fit: Adults aged 18 and older with confirmed mild autonomous cortisol secretion by dexamethasone suppression testing, benign adrenal imaging, and at least one related comorbidity (eg, obesity, dysglycemia, hypertension, dyslipidemia, or osteopenia/osteoporosis) are ideal candidates.
Not a fit: Patients with overt Cushing’s syndrome, malignant adrenal disease, or without confirmed autonomous cortisol secretion are unlikely to benefit from this intervention.
Why it matters
Potential benefit: If successful, the drug could safely lower cortisol exposure and potentially improve metabolic or bone-related complications linked to mild cortisol excess.
How similar studies have performed: Osilodrostat has been effective at lowering cortisol in patients with Cushing’s disease, but its use specifically for mild autonomous cortisol secretion is less well studied.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
* Provide written informed consent
* Stated willingness to comply with all study procedures and availability for the duration of the study
* Age ≥ 18 years
* Diagnosed with MACS
* At least 2 abnormal post-dexamethasone cortisol results:
i. 1 mg post-dexamethasone cortisol \>1.8 mcg/dL or ii. 8 mg post-dexamethasone cortisol \>1 mcg/dL
* Historical dexamethasone suppression test results can be used if performed within 24 months prior to enrollment.
* Adrenal imaging phenotype consistent with benign disease (adrenal adenoma/s, macronodular or micronodular adrenal hyperplasia)
* At least one of the following comorbidities:
* Obesity (BMI\>30 kg/m2)
* Dysglycemia
* Dyslipidemia
* Hypertension
* Osteopenia
* Osteoporosis
* Fragility fractures
* Ability to take oral medication and be willing to adhere to the study intervention regimen
* For persons of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of ≤ 5% per year during the treatment period and for 1 month after the last dose of study treatment.
Exclusion Criteria:
* Planned alternative therapy for MACS during the study period
* Current use of oral exogenous glucocorticoid therapy
* Current use of opioid therapy \>20 MME/day
* Planned use of oral exogenous glucocorticoid therapy
* Planned use of opioid therapy \>20 MME/day
* Use of injectable glucocorticoid within the last 6 weeks or anticipated glucocorticoid use during the study period.
* Hypokalemia of hypomagnesemia at baseline visit
* Prolonged QTc on baseline ECG
* Concomitant therapy with medications likely to lead to drug-drug interactions (based on PI review).
* Investigator's judgement based on history/physical examination that a comorbidity or concomitant medication may impact the hypothalamic-pituitary-adrenal axis or steroid metabolome
* Uncontrolled intercurrent illness including, but not limited to:
* Ongoing or active infection
* Symptomatic congestive heart failure
* Unstable angina pectoris
* Cardiac arrhythmia
* Psychiatric illness/social situations that would limit compliance with study requirements
* Pregnancy or lactation
* Known allergic reactions to osilodrostat
* Suspected false positive post-dexamethasone cortisol results due to increased metabolism, poor absorption, or noncompliance with dexamethasone.
* Treatment with another investigational drug or other intervention within lower than specific therapy washout period
Where this trial is running
Rochester, Minnesota
- Mayo Clinic — Rochester, Minnesota, United States (Recruiting)
Study contacts
- Principal investigator: Irina Bancos, MD — Mayo Clinic
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.