Isturisa Treatment in Mild Autonomous Cortisol Secretion( MACS)

NCT ID: NCT07247058

Last Updated: 2026-01-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-20
• Study Completion Date: 2029-03-31

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.

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.

Conditions

Mild Autonomous Cortisol Secretion (MACS)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Osilodrostat (Isturisa)

Intervention Type: DRUG

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.

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.

Intervention Type: DRUG

Other Intervention Names

Osilodrostat; Isturisa; LCI699

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Recordati Rare Diseases Inc

UNKNOWN

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amir Hamrahian, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Pooneh Jabbaripour Sarmadian, MD

Role: CONTACT

pjabbar1@jh.edu

667-208-8367

Tony Keyes

Role: CONTACT

akeyes1@jhmi.edu

410-550-6259

Facility Contacts

Amir Hamrahian, MD

Role: primary

ahamrah1@jhmi.edu

410-955-1578

Tony Keyes

Role: backup

akeyes1@jhmi.edu

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Other Identifiers

IRB00511675

Identifier Type: -

Identifier Source: org_study_id