The main study aim is the in vivo and ex vivo investigation of the expression and distribution of the GLP-1R in the pancreas of children (< 16 years) with proven endogenous congenital hyperinsulinism who qualify for surgery based on response to…
ID
Source
Brief title
Condition
- Endocrine disorders congenital
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The expression and distribution of the GLP-1R in the pancreas of children (<16
years) with proven endogenous congenital hyperinsulinism by comparison of
68Ga-NODAGA-exendin 4 PET/CT imaging data with autoradiography and histology
performed on specimens collected during surgery.
Secondary outcome
• Comparison of the sensitivity of 68Ga-NODAGA-exendin 4 PET/Ct and 18F-DOPA
PET/CT for the pre-operative localization of focal CHI and the discrimination
between focal and diffuse CHI.
• Analysis of the kinetics of radiotracer uptake in the pancreas of CHI
patients.
• Determination of the minimal injected dose of 68Ga-NODAGA-exendin 4 needed
for accurate imaging.
• Determination of the effective radiation dose received by children injected
with the calculated minimum dose of 68Ga-NODAGA-exendin 4.
• Assessment of the safety (side effects) of 68Ga-NODAGA-exendin 4 as compared
to 18F-DOPA.
• Calculation and comparison of the interobserver variability of
68Ga-NODAGA-exendin 4 PET/CT and 18F-DOPA PET/CT
• Evaluation of the clinical outcome parameters (laboratory parameters
(glucose) and dosage of medical treatment) after surgery
Background summary
We propose to improve the sensitivity and specificity of pre-operative imaging
for the localization of focal lesions in CHI and the discrimination between
focal and diffuse CHI. This by using a new tracer which binds the
glucagon-like-peptide-1 receptor (GLP-1R): 68Ga-NODAGA-exendin-4.
Study objective
The main study aim is the in vivo and ex vivo investigation of the expression
and distribution of the GLP-1R in the pancreas of children (< 16 years) with
proven endogenous congenital hyperinsulinism who qualify for surgery based on
response to medical treatment and genetic analysis (only patients with
genetically proven diffuse CHI will be excluded). 68Ga-NODAGA-exendin-4 PET/CT
imaging data will be compared with autoradiography and histology performed on
specimens collected during surgery.
Study design
Multicenter prospective imaging (pilot) study in which we will compare GLP-1R
imaging with the standard imaging technique for pre-operative imaging in
patients with CHI.
Intervention
68Ga-exendin PET/CT
Study burden and risks
Injection of the radiolabeled tracer may result in nausea and headache as has
been reported for (very high doses (10-100 µg) of) Byetta® in therapy studies.
In addition, a decrease of blood glucose levels (0.8 - 2.1 mmol/l has been
described after injection of 8 - 14 µg 111In-DTPA-exendin-4 in patients with
adult hyperinsulinemic hypoglycaemia (AHH). Importantly, regular monitoring of
glucose concentrations led to no serious episodes of hypoglycaemia. Therefore,
no side-effects are anticipated with injection of 0.032 µg/kg of radiolabeled
exendin. Patients will however be closely monitored, especially because the
compound has not been used before in children. Furthermore, a prophylactic
glucose infusion will be started 15 minutes before injection of radiolabeled
exendin.
The expected radiation dose will not exceed 13.2 mSv in newborns and declines
rapidly with age. In relation to the expected benefit in diagnostic imaging by
improving pre-operative non-invasive determination of the type of CHI and
localization of the focus of diseased beta cells with higher sensitivity and
specificity and the resulting impact on CHI treatment, this additional
radiation exposure is acceptable. Especially when taking into consideration
that the current challenges in pre-operative localization of focal CHI result
in considerable morbidity of the surgical treatment which causes these children
to experience severed side-effects and remain dependent on medication for the
rest of their lives.
Geert Grooteplein-Zuid 10
Nijmegen 6500 HB
NL
Geert Grooteplein-Zuid 10
Nijmegen 6500 HB
NL
Listed location countries
Age
Inclusion criteria
• Biochemically and clinically proven endogenous congenital hyperinsulinism:
- Unresponsive to medical treatment (diazoxide)
- Indication for 18F-DOPA PET/CT based on mutation analysis
• Standard imaging (18F-DOPA PET/CT) not older than 8 weeks
• <16 years old
• Informed consent signed by parents or legal guardians of the patient.
Exclusion criteria
• Genetically proven diffuse CHI (presenting with a homozygous or compound heterozygous ABCC8/KCNJ11 mutation)
• Calculated creatinine clearance below 40 ml/min
• Evidence of other malignancy than insulin producing tumors in conventional imaging (suspicious liver, bone and lung lesions based on CT)
• Age > 16 years
• No signed informed consent
Design
Recruitment
Medical products/devices used
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR201500269218-NL |
| CCMO | NL54275.000.15 |