Isturisa Treatment in Mild Autonomous Cortisol Secretion( MACS)

March 3, 2026 updated by: Johns Hopkins University

Isturisa in Management of Mild Autonomous Cortisol Secretion (MACS)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Mild autonomous cortisol secretion (MACS) is diagnosed in up to 48% of patients with incidentally discovered adrenal tumors or hyperplasia. Based on the finding of adrenal masses in 5% of adults undergoing cross-sectional imaging, the overall prevalence of MACS is about 1-2%. MACS is characterized by autonomous cortisol secretion without the overt symptoms of Cushing syndrome. It is usually associated with low ACTH and DHEAS levels as an indicator of autonomous cortisol secretion. The European Society of Endocrinology-European Network for the Study of Adrenal Tumors (ESE-ENSAT) and the American Association of Clinical Endocrinology (AACE) recommend a cortisol >1.8 μg/dL after 1 mg-DST to define MACS. Several metabolic abnormalities are associated with MACS, including increased cardiovascular disease, mood alteration, hypertension, osteoporosis, hyperglycemia, obesity, weight gain, and lipid abnormalities. Additionally, increased mortality has been reported in MACS patients. Given these complications and increased mortality, there is a need for effective management and treatment options for MACS.

This research aims to evaluate the efficacy and safety of Isturisa in patients with MACS to address the current gap in treatment strategies. By assessing how effectively Isturisa improves cardiometabolic disorders and monitoring its safety profile, the research will seek to provide a clearer understanding of its role as a treatment option in MACS patients who are not a surgical candidate or do not want to pursue surgery. This evaluation is crucial for developing more effective treatment options and improving management strategies for MACS, ultimately contributing to better patient management.

Study Type

Interventional

Enrollment (Estimated)

10

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Pooneh Jabbaripour Sarmadian, MD
  • Phone Number: 667-208-8367
  • Email: pjabbar1@jh.edu

Study Contact Backup

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Recruiting
        • Johns Hopkins University School of Medicine
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adults aged ≥18 years.
  • Diagnosis of mild autonomous cortisol secretion (MACS) defined by:
  • Serum cortisol >1.8 µg/dL after 1 mg overnight dexamethasone suppression test (DST).
  • Presence of adrenal adenoma confirmed by imaging (CT or MRI).
  • Ability to provide informed consent.
  • Willingness to undergo study procedures including DEXA scan and laboratory assessments.

Exclusion Criteria:

  • Known diagnosis of Cushing's syndrome or overt hypercortisolism.
  • Current or recent (within 3 months) treatment with glucocorticoids or medications affecting cortisol production (e.g., ketoconazole, metyrapone).
  • Severe hepatic impairment or renal failure.
  • Pregnancy or breastfeeding.
  • Known allergy or contraindication to osilodrostat (Isturisa).
  • Participation in another interventional clinical trial within the last 30 days.
  • Any medical or psychiatric condition that, in the investigator's judgment, may interfere with study participation or safety.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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).
Drug: 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.
Other Names:
  • LCI699
  • Isturisa
  • Osilodrostat

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in fasting glucose, HbA1c
Time Frame: Baseline, and then every 3 months up to 2 years
glycemic control: fasting glucose, HbA1c
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
Bone mineral density (g/cm²) measured by DEXA scan.
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 body weight will be measured at baseline and every follow-up visit (approximately every 3 months) throughout the 2-year treatment period with Isturisa.
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
Serum lipid profile (LDL-C, HDL-C, total cholesterol, triglycerides) will be assessed at baseline and every follow-up visit (approximately every 3 months) during the 2-year treatment period.
Baseline and every 3 months up to 2 years
Change in body composition (kg)
Time Frame: baseline, 1 year and 2 years
Body composition including lean mass and fat mass (kg) measured by DEXA scan.
baseline, 1 year and 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Quality of Life as assessed by Short Form -36 (SF-36)
Time Frame: Baseline and every 3 months up to 2 years
Assessment of changes in quality of life using the SF-36 Health Survey. The SF-36 consists of 36 items measuring 8 health domains, with total scores ranging from 0 to 100, where higher scores indicate better quality of life.
Baseline and every 3 months up to 2 years
Change in carotid intima-media thickness (CIMT)
Time Frame: Baseline, 1 year, and 2 years
Carotid intima-media thickness (milimeters) will be measured using carotid ultrasound to evaluate vascular changes associated with mild autonomous cortisol secretion. CIMT will be assessed at baseline and at follow-up imaging performed approximately every 12 months during the 2-year treatment period.
Baseline, 1 year, and 2 years
Change in Depression Scores as assessed by the Beck Depression Inventory-II
Time Frame: Baseline and every 3 months up to 2 years
Assessment of changes in depressive symptoms using the Beck Depression Inventory-II (BDI-II). The BDI-II is a 21-item validated questionnaire with total scores ranging from 0 to 63, where higher scores indicate more severe depressive symptoms.
Baseline and every 3 months up to 2 years
Change in adrenal adenoma/hyperplasia size (mm)
Time Frame: Baseline, 1 year, and 2 years
Adenoma maximal diameter (mm) measured on non-contrast CT at each imaging time point.
Baseline, 1 year, and 2 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Inflammatory Biomarkers
Time Frame: Baseline and every 3 months up to 2 years
Exploratory evaluation of changes in inflammatory biomarkers, specifically high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6), during treatment with Isturisa in patients with mild autonomous cortisol secretion (MACS). These markers are included in the optional research-specific procedures to assess potential inflammatory or physiologic effects of Isturisa beyond cortisol regulation.
Baseline and every 3 months up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Collaborators

Recordati Rare Diseases Inc

Investigators

  • Principal Investigator: Amir Hamrahian, MD, Johns Hopkins University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 2, 2026

Primary Completion (Estimated)

December 1, 2028

Study Completion (Estimated)

March 1, 2029

Study Registration Dates

First Submitted

November 19, 2025

First Submitted That Met QC Criteria

November 19, 2025

First Posted (Actual)

November 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 5, 2026

Last Update Submitted That Met QC Criteria

March 3, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00511675

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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