Pasireotide Therapy in Patients With Nelson's Syndrome
Nelson's syndrome, an expanding pituitary tumour, occurs in up to 30% of adults after bilateral adrenalectomy for Cushing's disease, for which no medical treatment exists. Plasma Adrenocorticotrophic hormone (ACTH) levels in these patients remain high, they are characteristically deeply pigmented, and may experience neurological effects as a consequence of the tumour. It is not known whether the tumour growth is due to the lack of cortisol feedback after adrenalectomy or whether the pituitary cells were preprogrammed to develop into a tumour.
There is a real need for an effective medical management for Nelson's syndrome. This is especially true given the increasing data on the somewhat disappointing longterm outcome of transsphenoidal surgery, and the increasing use of aparoscopic bilateral adrenalectomy for failures of pituitary surgery or even as primary therapy for Cushing's disease. Therefore, it is likely that there will be increasing numbers of patients attending endocrine centres worldwide with Nelson's syndrome following bilateral adrenalectomy as part of their management for Cushing's disease. In view of this it is important to investigate all potential avenues for the treatment of Nelson's syndrome and translate any benefits to patients.
This study, designed and initiated by the investigators, will assess if pasireotide reduces ACTH levels and tumour volume in patients with Nelson's syndrome. Patients will be recruited for a period of 32 weeks and receive 4 weeks of pasireotide twice daily and then 24 weeks of pasireotide long acting release therapy every 4 weeks. Over the 32 week protocol patients will make 12 visits for serial ACTH blood measurements and have 2 MRI scans to assess tumour volume.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open Label, Longitudinal Study of the Effects of Subcutaneous Acute and Chronic Pasireotide (som230) Therapy on Adrenocorticotrophic Hormone and Tumour Volume in Patients With Nelson's Syndrome|
- Serum ACTH levels in patients with Nelson's syndrome. [ Designated as safety issue: No ]
Early morning plasma ACTH sampled at 0, 1, 2, and 3 hours after morning hydrocortisone (HC) during 4 weeks of pasireotide 1200ug/day compared with levels at these respective time points found at baseline, and after chronic depot pasireotide 60mg i.m every 28 days:
Complete success: Fall in pre-HC plasma ACTH > 400ng/l, or 120 minutes after HC >200ng/l Partial success: Fall in pre-HC plasma ACTH < 399ng/l >200ng/l, or 120 minutes after HC <199ng/l >100ng/l No success: Fall in pre-HC plasma ACTH < 199ng/l, or 120 minutes after HC <99ng/l
- Tumour volume in patients with Nelson's syndrome. [ Designated as safety issue: No ]
Does Chronic Pasireotide Therapy Effect Tumour Volume?
H0= Pasireotide will not reduce tumour volume in patients with Nelson's syndrome.
H1= Pasireotide will reduce tumour volume in patients with Nelson's syndrome.
- Is the Pasireotide Therapy Used in this Study Safe and Tolerable in Nelson's Patients? [ Designated as safety issue: Yes ]
- Does tumour volume correlate with somatostatin receptor expression? [ Designated as safety issue: No ]
|Study Start Date:||March 2011|
|Barts and the London NHS Trust||Recruiting|
|London, United Kingdom|
|Contact: Scott Akker firstname.lastname@example.org|
|Principal Investigator: Scott Akker|
|The Christie Hospital NHS Foundation Trust||Recruiting|
|Manchester, United Kingdom|
|Contact: Peter Trainer email@example.com|
|Principal Investigator: Peter Trainer|
|Oxford University Hospitals NHS Trust||Not yet recruiting|
|Oxford, United Kingdom|
|Contact: Ashley Grossman firstname.lastname@example.org|
|Principal Investigator: Ashley Grossman|
|Sheffield Teaching Hospitals NHS Foundation Trust||Recruiting|
|Sheffield, United Kingdom, S10 2JF|
|Contact: John Newell-Price email@example.com|
|Principal Investigator: John Newell-Price|
|Principal Investigator:||John Newell-Price||Sheffield Teaching Hospitals NHS Foundation Trust|