Nelson SyndromePhase 2NCT01617733
Pasireotide Therapy in Patients With Nelson's Syndrome
A Phase 2 study testing Pasireotide in people with Nelson Syndrome, run by Sheffield Teaching Hospitals NHS Foundation Trust at 4 sites in United Kingdom.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Nelson Syndrome
- What is being tested?
- Pasireotide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 4 sitesUnited Kingdom
- Study dates
- Mar 2011to Dec 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
4 sites in 1 country.
United Kingdom4 sites
Barts and the London NHS Trust
London
The Christie Hospital NHS Foundation Trust
Manchester
Oxford University Hospitals NHS Trust
Oxford
Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield, S10 2JF
About this study
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
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.
Read the detailed description
As above
- Conditions
- Nelson Syndrome
- Being tested
- Pasireotide
- Medical subject headings
- Nelson Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PasireotideDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Pasireotide | Experimental | 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 Receives: Drug: Pasireotide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum ACTH levels in patients with Nelson's syndrome.
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
Measured: 0, 2, 4, 8, 12, 16, 20, 24, 28 weeks
Secondary outcomes (3)
Tumour volume in patients with Nelson's syndrome.
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.
Measured: 0 & 28 weeks
Is the Pasireotide Therapy Used in this Study Safe and Tolerable in Nelson's Patients?
Overall outcome measure
Measured: 0, 2, 4, 8, 12, 16, 20, 24, 28 weeks
Does tumour volume correlate with somatostatin receptor expression?
Tumour volume from MRI scan
Measured: 0 & 28 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2012 (estimated)
- Study startMar 2011
- Primary completionAug 2015
- Study completionDec 2015
Why it stopped: Inadequate patient recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Nelson SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis, The Christie NHS Foundation Trust, Oxford University Hospitals NHS Trust, Barts & The London NHS Trust
- Responsible party
- Sponsor
- Investigators
- John Newell-Price, Principal investigator, Sheffield Teaching Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01617733
- Sponsor's protocol ID
- STH15164
- Other IDs
- 2009-014457-33, 2009
- Status last verified
- Nov 2016
- First submitted
- 8 Jun 2012
- Last updated
- 2 Nov 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Daniel E, Debono M, Caunt S, Girio-Fragkoulakis C, Walters SJ, Akker SA, Grossman AB, Trainer PJ, Newell-Price J. A prospective longitudinal study of Pasireotide in Nelson's syndrome. Pituitary. 2018 Jun;21(3):247-255. doi: 10.1007/s11102-017-0853-3.
PubMed 29313180
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01617733
- Acronym / sponsor ID
- STH15164
- Conditions
- Nelson Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inadequate patient recruitment
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Novartis, The Christie NHS Foundation Trust, Oxford University Hospitals NHS Trust, Barts & The London NHS Trust
- Study start
- Mar 2011
- Primary completion
- Aug 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 12 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
As above
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pasireotide | Experimental | Drug: Pasireotide4 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 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pasireotide4 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 | Drug | Pasireotide |
Primary outcome
Serum ACTH levels in patients with Nelson's syndrome.
Time frame: 0, 2, 4, 8, 12, 16, 20, 24, 28 weeks
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
3 secondary outcomes
Tumour volume in patients with Nelson's syndrome.
Time frame: 0 & 28 weeks
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
Does tumour volume correlate with somatostatin receptor expression?
Time frame: 0 & 28 weeks
Results and safety
The study was stopped early (reason given: Inadequate patient recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2016.
- Derived from this study: PubMed 29313180Daniel E, Debono M, Caunt S, Girio-Fragkoulakis C, Walters SJ, Akker SA, Grossman AB, Trainer PJ, Newell-Price J. A prospective longitudinal study of Pasireotide in Nelson's syndrome. Pituitary. 2018 Jun;21(3):247-255. doi: 10.1007/s11102-017-0853-3.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Newell-Price principal investigator
Sheffield Teaching Hospitals NHS Foundation Trust
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pasireotide in people with Nelson Syndrome, run by Sheffield Teaching Hospitals NHS Foundation Trust at 4 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Inadequate patient recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum ACTH levels in patients with Nelson's syndrome. (time frame: 0, 2, 4, 8, 12, 16, 20, 24, 28 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01617733, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2016.