Combination Osilodrostat and Cabergoline in Cushing's Disease (COSCA-ECD)

University of Basrah

Status and phase: Invitation-only; Phase 4

Conditions: Cushing Disease Due to Increased ACTH Secretion

Treatments: Drug: osilodrostat; Drug: osilodrostat and cabergoline

Study type: Interventional

Funder types: Other

Identifiers

NCT07603466

05/13/26

Details and patient eligibility

About

Cushing disease remains a challenging endocrine disorder in which persistent or recurrent hypercortisolism often requires medical therapy after surgery or when surgery is not feasible. Combination medical therapy has emerged as a rational strategy to improve biochemical control through complementary mechanisms while potentially reducing treatment escape and dose-related toxicity. Cabergoline exerts pituitary D2-receptor-mediated inhibition of ACTH secretion and may provide partial cortisol control in selected patients, although treatment escape and variable durability remain important limitations. Osilodrostat is a potent 11β-hydroxylase inhibitor that produces rapid and often substantial reductions in cortisol secretion, with clinical improvement in metabolic and cardiovascular features of hypercortisolism. The osilodrostat-cabergoline combination is mechanistically attractive because it pairs central ACTH suppression with peripheral blockade of cortisol synthesis, but published evidence remains limited to small real-world experiences and does not yet define optimal sequencing, dosing, or long-term benefit. Safety considerations include adrenal insufficiency from overtreatment, osilodrostat-associated hypertension from mineralocorticoid precursor accumulation, and hyperandrogenism due to steroid precursor shunting.

Combination medical therapy in Cushing disease is a promising individualized approach, and the osilodrostat-cabergoline pairing is biologically plausible and potentially effective, but current literature is insufficient to support firm recommendations regarding efficacy, safety, or patient selection.

The study aims to evaluate whether a combination can result in rapid, more control of Cushing's disease (clinically and biochemically)? Can cabergoline reduces Osilodrostat dose requirement, reduces Osilodrostat related mineralocorticoid and hyperandrogenism side effects?

Full description

In this study, adult patients with active CD (with or without previous TSS or radiotherapy) will be enrolled. Investigators will start treatment for all with Osilodrostat using up-titrating doses on bi-weekly bases. Then the patients will be randomized into two groups. For the first group, carbergoline with escalating doses will be added. For the second group, the patients will continue osilodrostat treatment with increasing doses. Through the period of the study interventions, the patients will be followed clinically, and biochemical looking for treatment related efficacy and safety.

Enrollment: 50 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Cushing's disease: Not treated or received treatment (TSS and/or radio surgery). And
• Active disease confirmed with repeated two biochemical tests (1-mg overnight dexamethasone suppression test and late night salivary cortisol), And
• Inappropriate ACTH elevation, And
• Positive ACTH response to desmopressin stimulation test, And
• MRI finding of pituitary adenoma.

Exclusion criteria

• Severe hepatic impairment (Child-Pugh C).
• Pregnancy.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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50 participants in 2 patient groups

Osilodrostat alone

Active Comparator group

Description:

Osilodrostat up to 15 mg daily

Treatment:

Drug: osilodrostat

Combination osilodrostat and cabergoline

Active Comparator group

Description:

Osilodrostat up to 5 mg daily plus Cabergoline up to 3 mg weekly

Treatment:

Drug: osilodrostat and cabergoline