|- candidate number||3623|
|- NTR Number||NTR1379|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||17-jul-2008|
|- Secondary IDs||NL13656.078.07 |
|- Public Title||Stepwise medical treatment of Cushing's disease|
|- Scientific Title||Stepwise Medical Treatment of Cushing’s Disease: a prospective, open label, multi-center trial with SOM230 mono- and combination therapy with dopamine agonists and ketoconazole for treatment of Cushing’s disease|
|- hypothesis||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. |
|- Healt Condition(s) or Problem(s) studied||Cushing's disease, Cortisol, Dopamine agonists , Ketoconazole|
|- Inclusion criteria||1. Both naïve patients with Cushing’s disease and patients with residual hypercortisolism after recent transsphenoidal adenomectomy are eligible for enrolment. |
2. Finally, patients with recurrent Cushing’s disease can also be included.
|- Exclusion criteria||1. Patients with poorly controlled diabetes mellitus indicated by a HbA1c % > 8.5 %.|
2. Patients with a disturbed liver function indicated by serum bilirubin, ALAT, ASAT or alkaline phosphatase levels > 2.5 x ULN.
3. Patients with renal insufficiency indicated by serum creatinine levels > 2.0 x ULN
4. Patients who are already treated with cortisol lowering therapy can only be included after a wash-out period of 4 weeks followed by re-assessment for hypercortisolism
5. Patients with symptomatic cholelithiasis.
6. Patients with a history of pituitary irradiation.
7. Pregnant patients or patients who desire to become pregnant during the study period.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||Single arm|
|- planned startdate ||1-sep-2007|
|- planned closingdate||1-sep-2009|
|- Target number of participants||16|
|- Interventions||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.
|- Primary outcome||- Achievement of normocortisolism|
|- Secondary outcome||- Improvement of clinical symptoms of Cushing's disease|
- Quality of life
- Glucose tolerance
- Pituitary adenoma size
- Bone metabolism (bone mineral density, bone formative and resorptive markers)
|- Timepoints||Total study duration is 80 days, evaluation of patients will be performed at day 10, day 26, day 54 and day 80.|
|- Trial web site||N/A|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||Dr. R.A. Feelders|
|- CONTACT for SCIENTIFIC QUERIES||Dr. R.A. Feelders|
|- Sponsor/Initiator ||Erasmus Medical Center, Department of Internal Medicine |
(Source(s) of Monetary or Material Support)
|Novartis Pharma B.V.|
|- Brief summary||In this trial patients with Cushing's disease will be treated medically using a stepwise approach with respectively SOM230, cabergoline and ketoconazole.|
|- Main changes (audit trail)|
|- RECORD||17-jul-2008 - 23-jul-2008|