Isturisa treatment for people with mild autonomous cortisol secretion (MACS)

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 Phase 4 interventional study gives adults with imaging-confirmed adrenal adenomas and MACS oral osilodrostat (Isturisa) and compares metabolic, cardiovascular, body composition, bone density, and quality-of-life measures to baseline. Participants undergo regular laboratory testing, DEXA scans, blood pressure and weight monitoring, and psychological and quality-of-life assessments over the treatment period. Safety and adverse events are recorded throughout to characterize the drug's tolerability in this population. The trial focuses on non-surgical MACS patients to define a medical treatment option for cortisol excess without overt Cushing syndrome.

Why it matters

Who can join: the full rules

* Age \>18 years old with confirmed mild autonomous cortisol secretion (MACS) Cushing's syndrome, defined by:

  * At least two abnormal 1 mg Dexamethasone suppression tests (Cortisol \> 1.8 ug/dL at 8-9 am after taking 1 mg dexamethasone at 11 pm) with appropriate dexamethasone level for the assay (last level within 3 months before enrollment).
  * Having at least two early morning fasting ACTH \<15 pg/mL (last level within 3 months before enrollment)
* Presence of at least one of the following comorbidities:

  * The presence of prediabetes or Type 2 diabetes mellitus (T2DM): fasting plasma glucose ≥100 mg/dL and/or 2-hour Oral Glucose Tolerance Test (OGTT) glucose ≥140 mg/dL, or HbA1c ≥5.7%
  * Systolic hypertension is defined as a mean Systolic Blood Pressure (SBP) ≥130 mmHg after 5 min rest in a seated position (mean of 3 blood pressure measurements 5 minutes apart) irrespective of the number of anti-hypertensive medications.
  * BMI \>30 kg/m2
* The presence of an adrenal adenoma or hyperplasia, as determined by CT or MRI studies
* Negative urine pregnancy test at Baseline (urine) for women of childbearing potential

Exclusion criteria:

* Has severe, uncontrolled hypertension (mean SBP \>170 mm Hg or mean Diastolic Blood Pressure (DBP) \>110 mm Hg at Screening)
* Has poorly controlled DM (HbA1c \>11% at Screening).
* Has abnormal liver test results (total bilirubin \>1.5×ULN or elevated alanine aminotransferase or aspartate aminotransferase \>3×ULN at Baseline).
* Has severe renal insufficiency (glomerular filtration rate ≤29 mL/min at Baseline).
* Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism.
* Has prolonged QT interval corrected for heart rate using Fridericia's equation (QTcF) (\>450 ms for men and \>470 ms for women) with a normal QRS interval (\<120 ms) or QTcF interval \>500 ms with wide QRS interval (≥120 ms).
* Has persistent atrial fibrillation.
* Has uncorrected hypokalemia.
* Has used or plans to use any treatments for MACS within 12 weeks before Screening and throughout the study, including metyrapone, mifepristone, ketoconazole, fluconazole, or any investigational drug for the treatment of hypercortisolism.
* Has adrenocortical carcinoma, or the adrenal images are suspicious for an underlying malignancy.
* Has autonomous co-secretion of aldosterone.
* Has plans for adrenalectomy or nodulectomy during the study.
* Pregnancy, lactating, or intends to become pregnant in the next 2 years.
* Female patients of childbearing potential who cannot use a highly effective method of contraception, including all women \<50 years old, women whose surgical sterilization was performed \<6 months ago.

Where it's running

• Johns Hopkins University School of Medicine
  Baltimore, Maryland, United States Recruiting

Study contacts

• Principal investigator: Amir Hamrahian, MD — Johns Hopkins University
• Study coordinator: Pooneh Jabbaripour Sarmadian, MD
• Email: pjabbar1@jh.edu
• Phone: 667-208-8367

Similar studies

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

• Adrenal Diseases in Modena: A Patient Registry at Modena University Hospital

  This study collects medical histories and treatment data from patients with adrenal diseases to see how they are diagnosed and managed in Modena.

  Recruiting Azienda Ospedaliero-Universitaria di Modena · Modena, Modena · NCT07920198

• Tirzepatide after adrenalectomy for MACS

  This study tests whether adding tirzepatide after adrenalectomy helps control blood pressure and improve metabolic health in adults with mild autonomous cortisol secretion.

  Recruiting Phase 2 University of Pittsburgh · Pittsburgh, Pennsylvania · NCT07573163

• 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.

  Recruiting University of Texas Southwestern Medical Center · Dallas, Texas · NCT07361874

• Metyrapone versus osilodrostat for metabolic autonomous cortisol secretion (MACS)

  This trial will test whether metyrapone or osilodrostat better lowers cortisol and improves health in adults with mild autonomous cortisol secretion (MACS) who are not having surgery.

  Recruiting Phase 4 Laikο General Hospital, Athens · Athens · NCT07268222

• 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

• Detecting cortisol secretion issues in patients with adrenal incidentalomas

  This study is trying to see how common mild cortisol secretion problems are in people with adrenal incidentalomas and which tests work best to find them.

  Recruiting The Cleveland Clinic · Cleveland, Ohio · NCT06344143

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.