Stepwise medical treatment of Cushing's disease

In this trial patients with Cushing's disease will be treated medically using a stepwise approach with respectively SOM230, cabergoline and ketoconazole.

Currently, no effective, non-toxic medical therapy is available for Cushing's disease. Corticotroph adenomas express both somatostatin receptor subtype 5 and dopamine receptors. SOM230 is a new somatostatin analog which binds to 4 of 5 somatostatin receptor subtypes. In vitro studies show that somatostatin analogs and dopamine agonists may potentiate each others effects. Dopamine agonists are also effective in a subset of patients with Cushing's disease. Finally, ketoconazole has apart from its adrenolytic effects, inhibitory effects on ACTH secretion by and cell growth of corticotroph tumor cells which are potentiated by SOM230. By combining these partially independent medical therapies which act through differential mechanisms, we aim at maximizing the number of patients with Cushing’s disease in whom normalization of cortisol production can be achieved.

Total study duration is 80 days, evaluation of patients will be performed at day 10, day 26, day 54 and day 80.

Patients with Cushing's disease will be treated medically by the following stepwise approach:

- Patients will start with SOM230 (sc.), if this is not effective cabergoline (p.o.) will be added in an increasing dosage, finally when hypercortisolism persists, ketoconazole (p.o.) is added.

Total study duration is 80 days.