Recruiting
Phase 4

Isturisa

Sponsor:

Johns Hopkins University

Code:

NCT07247058

Conditions

Mild Autonomous Cortisol Secretion (MACS)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Osilodrostat (Isturisa)

Study Details

Brief summary:

To characterize the impact of Isturisa on clinical features and comorbidities associated with MACS. The investigators hypothesize that patients treated with Isturisa will exhibit significantly better metabolic indicators (such as fasting glucose, HbA1c, and lipid profile), blood pressure, weight, body composition and bone mineral density than at Baseline. The investigators also assess the effect of Isturisa on quality of life and psychological symptoms in patients with MACS. The investigators hypothesize that treatment with Isturisa will lead to significant improvements in quality-of-life scores and reductions in depression scores compared to Baseline.

Conditions

Mild Autonomous Cortisol Secretion (MACS)

Study ID

NCT07247058

Start date

Feb 2, 2026

Status verified date

Oct, 2026

Completion date

Mar, 2029

Anticipated

Primary completion date

Dec, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

  • 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.

Study Design

Enrollment

10 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Isturisa Treatment Arm

Participants diagnosed with Mild Autonomous Cortisol Secretion (MACS) will receive Osilodrostat (Isturisa) as an investigational treatment. The intervention aims to evaluate comorbidities associated with MACS after the initiation of osilodrostat(Isturisa).

Interventions

Osilodrostat (Isturisa)

The intervention aims to evaluate the impact of osilodrostat on cardiometabolic outcomes, bone mineral density, body composition, adrenal tumor size or hyperplasia, and biochemical markers of cortisol excess.

Primary outcome measure

  • Change in fasting glucose, HbA1c [ Time Frame: Baseline, and then every 3 months up to 2 years ]
  • Change in bone mineral density (g/cm²) [ Time Frame: Baseline, 1 year, and 2 years ]
  • Change in body weight (kg) from baseline during Isturisa treatment [ Time Frame: Baseline and every 3 months up to 2 years ]
  • Change in lipid profile from baseline during Isturisa treatment [ Time Frame: Baseline and every 3 months up to 2 years ]
  • Change in body composition (kg) [ Time Frame: baseline, 1 year and 2 years ]

Central Contacts and Locations

Central contacts

Pooneh Jabbaripour Sarmadian, MD

667-208-8367pjabbar1@jh.edu

Tony Keyes

410-550-6259akeyes1@jhmi.edu

Locations

Johns Hopkins University School of Medicine

Recruiting

Baltimore, Maryland, United States, 21205

Contacts

Amir Hamrahian, MD

410-955-1578ahamrah1@jhmi.edu

Tony Keyes

akeyes1@jhmi.edu

More Information

Sponsor

Johns Hopkins University

Last update posted

Oct 23, 2026

Last verified

Oct, 2026

Keywords

  • MACS
  • Mild Autonomous Cortisol Secretion
  • Adrenal Adenoma
  • Osilodrostat
  • Isturisa
  • Body Composition
  • Metabolic Outcomes
  • Subclinical Cushing Syndrome
  • Adrenal hyperplasia
  • Carotid intima thickness
  • Bone mineral density
  • Hypertension
  • Glycemic control

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-24. This information was provided to ClinicalTrials.gov by Johns Hopkins University on 2026-10-23. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.