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

15 de mayo de 2026 actualizado por: Haider Ayad Alidrisi, University of Basrah

Combination Osilodrostat and Cabergoline Versus Osilodrostat Alone in Cushing's Disease in Iraq: Assessment of Efficacy and Safety

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?

Descripción general del estudio

Estado

Inscripción por invitación

Condiciones

Intervención / Tratamiento

Descripción detallada

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.

Tipo de estudio

Intervencionista

Inscripción (Estimado)

50

Fase

  • Fase 4

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • Irak
      • Basra, Irak, 61001
        • Faiha Specialized Diabetes, Endocrine, and Metabolism Center
      • Karbala, Irak
        • Al-Hassan Metabolism Endocrine and Diabetes Center
      • Mosul, Irak
        • Al-Waffa Specialized Center for Diabetes and Endocrinology
      • Najaf, Irak
        • Najaf Specialized Diabetes and Endocrine Center
      • Nasiriyah, Irak
        • Thi-Qar Specialized Diabetes, Endocrine and Metabolism Center

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

  • Adulto
  • Adulto Mayor

Acepta Voluntarios Saludables

No

Descripción

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.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: No aleatorizado
  • Modelo Intervencionista: Asignación Secuencial
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Comparador activo: Osilodrostat alone
Osilodrostat up to 15 mg daily
Droga: osilodrostat
1 mg (pill) twice daily for two weeks, titrated to 2.5 mg (5 mg pill divided) twice daily for two weeks, then 7.5 (half 5 mg pill and 5 mg pill) for four weeks, then 10 mg (5 mg pill twice daily) for four weeks, then 15 mg (5 mg pill thrice daily).
Comparador activo: Combination osilodrostat and cabergoline
Osilodrostat up to 5 mg daily plus Cabergoline up to 3 mg weekly
Droga: osilodrostat and cabergoline
1 mg (pill) twice daily for two weeks, titrated to 2.5 mg (5 mg pill divided) twice daily for two weeks, then Add: Cabergoline 0.5 mg twice weekly for four weeks, titrated to 1 mg twice weekly for four weeks, then 1 mg thrice weekly.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Changes in serum cortisol
Periodo de tiempo: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, 48 weeks.
serum cortisol (8-9 am and 6-7 pm).
At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, 48 weeks.
Number of patients achieved serum cortisol (7-12 Mg/dL)
Periodo de tiempo: 4 weeks, 8 weeks, 12 weeks, 24, weeks, 36 weeks, and 48 weeks.
measurement of 8-9 am serum cortisol.
4 weeks, 8 weeks, 12 weeks, 24, weeks, 36 weeks, and 48 weeks.
Changes in Cushing 's Quality-of-Life questionnaire 12-items (CushingQoL) score for the patients quality of life.
Periodo de tiempo: At 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Changes in CushingQoL (12 items) questionnaire. The lowest score is 12 and highest score is 60. The highest the score, the better life quality and clinical improvement in Cushing syndrome.
At 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Changes in the patients' Body weight (kg)
Periodo de tiempo: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
measurement of the patients' body weight using scale in the early morning and fasting, bare feet, light clothes, using electronic scale.
At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Changes in the patients' Blood pressure (increase or decrease) and increase or decrease requirements for blood pressure lowering medications.
Periodo de tiempo: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Measurement of the patients' blood pressure (SBP/DBP mmHg) using standard electronic arm cuff blood pressure machine.
At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Changes in HbA1c (%)
Periodo de tiempo: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
measurement of the patients HbA1c % using BioRad D10
At 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Assessment of clinical hyperandrogenic features (acne and hirsutism), whether increase or decrease for female patients
Periodo de tiempo: At 12 weeks, 24 weeks, 36 weeks, and 48 weeks.

Acne will be assessed by clinical examination and reported as improved or increased.

Hirsutism will be assessed using the changes in the modified Ferrimann-Gallwey (mFG) score (0 - 36), the highest the score, the more severe hirsutism.
At 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Changes in plasma ACTH
Periodo de tiempo: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
measurement of early morning plasma ACTH (pg/ml)
At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Changes in serum dehydroepiandrosterone acetate (Mg/dl)
Periodo de tiempo: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
measurement of serum dehydroepiandrosterone acetate (Mg/dl)
At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Changes in the corrected QT interval on electrocardiograph (ECG).
Periodo de tiempo: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Performance of ECG for assessment and record of the c QT interval.
At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Changes in serum potassium
Periodo de tiempo: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
measurement of serum potassium
At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Development of symptoms of hypoadrenalism
Periodo de tiempo: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Development of symptoms of hypoadrenalism in the form of (anorexia, nausea, vomiting, fatigue, abdominal pain, dizziness, and hypotension)
At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Number of patients will have morning serum cortisol less than (5 Mg/dl)
Periodo de tiempo: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
measurement of serum cortisol in the morning and fasting state.
At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.

Otras medidas de resultado

Medida de resultado
Medida Descripción
Periodo de tiempo
Other drug related side effects
Periodo de tiempo: At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.
Side effects of Osilodrostat and cabergoline
At 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks.

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

University of Basrah

Investigadores

  • Investigador principal: Haider A Alidrisi, Univeristy of basrah, Faiha Specialized Diabetes, Endocrine, and Metabolism Center
  • Investigador principal: Ibrahim H Hussein, MD, Univeristy of basrah, Faiha Specialized Diabetes, Endocrine, and Metabolism Center
  • Silla de estudio: Abbas A Mansour, Univeristy of basrah, Faiha Specialized Diabetes, Endocrine, and Metabolism Center

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Publicaciones Generales

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

11 de mayo de 2026

Finalización primaria (Estimado)

1 de junio de 2028

Finalización del estudio (Estimado)

1 de agosto de 2028

Fechas de registro del estudio

Enviado por primera vez

11 de mayo de 2026

Primero enviado que cumplió con los criterios de control de calidad

15 de mayo de 2026

Publicado por primera vez (Actual)

22 de mayo de 2026

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

22 de mayo de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

15 de mayo de 2026

Última verificación

1 de mayo de 2026

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • 05/13/26

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

SÍ

Descripción del plan IPD

Only IPD used in the results publication.

Marco de tiempo para compartir IPD

Beginning 3 months and ending 3 years after the publication of results.

Tipo de información de apoyo para compartir IPD

  • PROTOCOLO DE ESTUDIO
  • SAVIA

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

producto fabricado y exportado desde los EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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