Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03189953 |
| Other study ID # |
NL50643.091.14 |
| Secondary ID |
2014-003167-3860 |
| Status |
Completed |
| Phase |
Phase 1/Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
April 2015 |
| Est. completion date |
May 2021 |
Study information
| Verified date |
June 2021 |
| Source |
Radboud University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
In order to improve the sensitivity and specificity of pre-operative imaging localization of
foci in adult endogenous hyperinsulinemic hypoglycaemia (AHH) we aim to evaluate a novel
promising imaging compound targeting the glucagon-like peptide-1 receptor (GLP-1R),
68Ga-NODAGA-exendin 4. With the currently used imaging techniques, only about 70-80% of
insulin producing pancreatic neuroendocrine tumors (IPPNET) can be successfully visualized.
Therefore, we propose to compare GLP-1R PET imaging to the standard imaging techniques in
patients scheduled for surgical removal of the tumour. These highly relevant data will allow
us to interpret the benefits of GLP-1R-imaging over other imaging techniques for the
diagnosis of IPPNET in AHH patients. Since pre-operative localization of foci in AHH remains
challenging and frequently still leading to futile surgery or unnecessary partial
pancreatectomy, a more sensitive and specific imaging technique would be of great value.
Description:
Adult endogenous hyperinsulinaemic hypoglycaemia The most common form of functional
neuroendocrine tumours of the pancreas are insulin producing pancreatic neuroendocrine tumors
(IPPNET). These tumors are rare and have an incidence of 1-4 newly diagnosed cases per 1
million per year and are malignant in about 10% of the cases. Another cause of AHH is
nesidioblastosis, or adult beta cell hyperplasia. It is difficult to exactly determine the
incidence of the disease, but it appears that in approximately 5% of the cases of AHH
nesiodioblastosis may be the underlying pathology, while IPPNET are responsible for the
majority of the cases. The pathophysiological cause of nesidioblastosis is not well
understood, but the rising incidence of the AHH as a consequence of gastric bypass surgery
for morbid obesity (although often reversible in these patients) may suggest an association
with metabolic and hormonal changes.
For IPPNET, surgical removal of the tumour is the therapy of choice and is considered
curative in case of a benign tumour. Optimal preoperative localization of the lesion is
warranted in order to reduce morbidity by helping to optimize the surgical procedure.
Successful preoperative localization of IPPNET is a challenging problem since approximately
30% of IPPNET cannot be visualized using the conventional imaging techniques CT and/or MRI
and endoscopic ultrasound. Selective arterial stimulation with calcium with simultaneous
venous sampling (ASVS) has been described to have a sensitivity and specificity of almost 90%
in identifying IPPNET. This is, however, an invasive technique which is accompanied by an
risk for complications. Functional imaging with somatostatin (sst) receptor scintigraphy
(SRS) and SPECT/CT are able to detect less than 50% of benign IPPNET because of low or absent
expression of sst receptor subtypes 2 and 5, which bind octreotide with high affinity. PET
with 68Ga-labeled sst analogs has a higher sensitivity for smaller lesions than SRS. Also
11C-5-HTP and 18F-DOPA, which are used as PET tracers for the detection of IPPNET in some
centers may be more sensitive than SRS and CT with 11C-5-HTP showing the most accurate
visualization. However, when compared to intra-operative findings, 2 out of 6 IPPNET could
still not be detected preoperatively. Palpation and intra-operative ultrasound will allow
identifying the lesion in approximately 70-80% of cases. However, it remains a challenge to
find small or multiple tumours in the pancreas and partial pancreatectomy is frequently
required, especially if the lesion is located close to the pancreatic duct. Precise
preoperative localization of the IPPNET is therefore critical to minimize surgical
intervention. If no IPPNET can be identified pre- or perioperatively, the diagnosis of
nesidioblastosis may be established by resection and histopathologic evaluation of the
pancreatic tail. If nesidioblastosis is present, partial pancreatectomy is required; the
challenge is to remove enough tissue in order to avoid hypoglycaemia while keeping enough
functional endocrine pancreatic tissue so that the patient does not become diabetic.
Currently, with the risk of reoperation being considered lower than the consequences and
complications of diabetes, surgeons usually choose a fairly conservative approach.
Imaging of diseased beta cells Visualization of the beta cells by a highly specific
radiotracer with which high target-to background ratios can be obtained would benefit
preoperative visualization of IPPNET in patients with AHH. Reliable visualization of diseased
beta cells would then benefit the optimization of treatment of patients with AHH. An
innovative method for imaging of beta cells could allow to optimally guide surgical
interventions In addition, this novel approach could lead to a minimization of side-effects
from the treatment.
Targeting of the GLP-1 receptor In this study we will compare the sensitivity and specificity
of pre-operative imaging of IPPNET by GLP-1R scanning to the current standard imaging
techniques.
