Low-dose (1 mg) osilodrostat for mild autonomous cortisol secretion

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• Mayo Clinic
  Rochester, Minnesota, United States Recruiting

Study contacts

• Principal investigator: Irina Bancos, MD — Mayo Clinic

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Ketoconazole's effect on the daily cortisol rhythm in MACS

  The study tests whether a single 400 mg dose of ketoconazole can modify the daily cortisol rhythm in adults with Mild Autonomous Cortisol Secretion (MACS) compared with healthy volunteers.

  Recruiting Phase 1 National Institutes of Health Clinical Center (CC) · Bethesda, Maryland · NCT07649317

• Adrenalectomy versus semaglutide for metabolic health in mild autonomous cortisol secretion

  We are testing whether removing the adrenal gland or treating with semaglutide better improves insulin resistance and other metabolic measures in adults with mild autonomous cortisol secretion, and comparing semaglutide effects to matched adults without adrenal tumors.

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• Metyrapone for Mild Autonomous Cortisol Secretion

  This study tests whether taking metyrapone by mouth for six months can safely reduce cortisol excess in adults with MACS compared with a placebo.

  Recruiting Phase 2 Mayo Clinic · Rochester, Minnesota · NCT07138274

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.