Isturisa Treatment in Mild Autonomous Cortisol Secretion( MACS)

Johns Hopkins University

Status and phase: Enrolling; Phase 4

Conditions: Mild Autonomous Cortisol Secretion (MACS)

Treatments: Drug: Osilodrostat (Isturisa)

Study type: Interventional

Funder types: Other

Identifiers

NCT07247058

IRB00511675

Details and patient eligibility

About

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.

Full 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.

Enrollment: 10 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

Isturisa Treatment Arm

Experimental group

Description:

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).

Treatment:

Drug: Osilodrostat (Isturisa)