- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01617733
Pasireotide Therapy in Patients With Nelson's Syndrome
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
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 Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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London, United Kingdom
- Barts and the London NHS Trust
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Manchester, United Kingdom
- The Christie Hospital NHS Foundation Trust
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Oxford, United Kingdom
- Oxford University Hospitals NHS Trust
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Sheffield, United Kingdom, S10 2JF
- Sheffield Teaching Hospitals NHS Foundation Trust
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- To be verified at Visit one and confirmed at Visit two
- Male or female patients aged 18-80 years
- Signs and symptoms consistent with Nelson's Syndrome
- Biochemistry consistent with Nelsons syndrome: failure to suppress plasma ACTH to less than 200 pg/ml at 2 hours following morning dose of hydrocortisone
- Negative pregnancy test where applicable
Exclusion Criteria:
- Received any prior or current treatment with a pasireotide or other somatostatin analogue.
- Requires surgery for recent significant deterioration in visual fields or other neurological signs related to tumour mass.
- Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis, or persistent ALT, AST, alkaline phosphates 2X> upper limit of normal, or total bilirubin 1.5X> upper limit of normal.
- Patients with symptomatic cholelithiasis
- Abnormal clinical laboratory values considered by the Investigator to be clinically significant and which could affect the interpretation of the study results
- QTcF interval as measured by ECG >480msecs
- Any current or prior medical condition that may, in the opinion of the Investigator, interfere with the conduct of the study or evaluation of the results.
- Female patients who are pregnant or lactating, or of childbearing potential and not practising a medically acceptable method of birth control. Medically acceptable methods include including the oral contraceptive pill, intrauterine devices, mechanical methods (e.g. vaginal diaphragm, vaginal sponge, or condom with permicidal jelly).
- History of alcohol or drug abuse in the sixmonth period prior to Visit 1, or who plan to take an investigational
- History of alcohol or drug abuse in the six month period prior to Visit 1, or who plan to take an investigational drug for another study during this study.
- History of noncompliance to medical regimes or who are considered potentially unreliable.
- Pituitary radiotherapy within the last 1 year prior to study entry.
- Unable to complete the entire study for any reason.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Pasireotide
4 Weeks pasireotide 0.6mg s/c injections twice daily followed by 24 weeks treatment with pasireotide LAR 60mg every 28 days with dose reductions if poor tolerability is encountered
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4 Weeks pasireotide 0.6mg s/c injections twice daily followed by 24 weeks treatment with pasireotide LAR 60mg every 28 days with dose reductions if poor tolerability is encountered
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Serum ACTH levels in patients with Nelson's syndrome.
Time Frame: 0, 2, 4, 8, 12, 16, 20, 24, 28 weeks
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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 |
0, 2, 4, 8, 12, 16, 20, 24, 28 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Tumour volume in patients with Nelson's syndrome.
Time Frame: 0 & 28 weeks
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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. |
0 & 28 weeks
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Is the Pasireotide Therapy Used in this Study Safe and Tolerable in Nelson's Patients?
Time Frame: 0, 2, 4, 8, 12, 16, 20, 24, 28 weeks
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Overall outcome measure
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0, 2, 4, 8, 12, 16, 20, 24, 28 weeks
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Does tumour volume correlate with somatostatin receptor expression?
Time Frame: 0 & 28 weeks
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Tumour volume from MRI scan
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0 & 28 weeks
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: John Newell-Price, Sheffield Teaching Hospitals NHS Foundation Trust
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neoplasms
- Neoplasms by Site
- Endocrine System Diseases
- Disease
- Endocrine Gland Neoplasms
- Hypothalamic Diseases
- Pituitary Diseases
- Pituitary Neoplasms
- ACTH-Secreting Pituitary Adenoma
- Syndrome
- Nelson Syndrome
- Physiological Effects of Drugs
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Pasireotide
Other Study ID Numbers
- STH15164
- 2009-014457-33 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Nelson Syndrome
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Neumedicines Inc.Department of Health and Human ServicesCompletedHematopoietic Syndrome Due to Acute Radiation SyndromeUnited States
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Ministry of Public Health, Democratic Republic...National Institutes of Health (NIH); Oregon Health and Science University; National... and other collaboratorsCompletedNeurotoxicity Syndrome, Cassava | Neurotoxicity Syndrome, Cyanate | Neurotoxicity Syndrome, Cyanide | Neurotoxicity Syndrome, ThiocyanateCongo, The Democratic Republic of the
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Mahidol UniversityCompletedSubacromial Impingement Syndrome | Shoulder Impingement Syndrome | Subacromial Pain Syndrome | Subacromial Impingement | Impingement Syndrome, ShoulderIndonesia
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Cliniques universitaires Saint-Luc- Université...TerminatedMultiple Organ Dysfunction Syndrome | SEPTIC SHOCK | SEPSIS SYNDROMEBelgium
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University of PennsylvaniaRecruitingCRS - Cytokine Release Syndrome | HLHUnited States
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University of ManitobaTerminatedPatellofemoral Pain Syndrome | Anterior Knee Pain Syndrome | Patellofemoral SyndromeCanada
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Massachusetts General HospitalUniversity of California, San DiegoNot yet recruitingAuto-Brewery Syndrome | Gut Fermentation SyndromeUnited States
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University of NottinghamMedical Research Council; National Institute for Health Research, United KingdomRecruitingFrail Elderly Syndrome | Frailty | Frailty SyndromeUnited Kingdom
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Riphah International UniversityCompleted
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