Congenital HyperinsulinismGLP-1-CHINCT03768518
GLP-1 Receptor Expression in CHI
An observational study of Congenital Hyperinsulinism, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
The primary objective is the in vivo and ex vivo investigation of the expression and distribution of the GLP-1R in the pancreas of CHI patients. Read more about this study
- Who is it for?
- Ages Up to 16 years
- Conditions the study is for
- Congenital Hyperinsulinism
- What is being tested?
- 68Ga-exendin-4 PET/CT
- How many people
- 40 participants
- Where
- 1 siteNetherlands
- Study dates
- 7 Feb 2018to 1 Feb 2019
- Phase
- Observational
- 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 Up to 16 years
- All sexes
- No healthy volunteers
- Child
Study population: patients (<16 years) with biochemically proven endogenous congenital hyperinsulinism
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Radboudumc
Nijmegen, 6500HB
Marti Boss, +31243667243, marti.boss@radboudumc.nl
About this study
Official title: The Physiology of Glucagon-like-peptide-1 Espression in Patients With Endogenous Hyperinsulinism: Correlation With Histopathology
The primary objective is the in vivo and ex vivo investigation of the expression and distribution of the GLP-1R in the pancreas of CHI patients.
Read the detailed description
Congenital hyperinsulinism (CHI) is a rare disease of infants characterized by the presence of functionally defective non-neoplastic beta-cells with inappropriate (over-) secretion of insulin, leading to life-threatening hypoglycaemia. Beta cells specifically express the glucagon-like-peptide-1 (GLP-1R), which could be a promising target for diagnostic and therapeutic purposes. In this study we propose to investigate the physiology of GLP-1 receptor expression in CHI. Expression of the GLP-1 receptor will be quantified in vivo by 68Ga-NODAGA-exendin-4 PET/CT. This data will be compared with post-surgical autoradiography and morphometric determinations.
Furthermore, we will evaluate 68Ga-exendin-4 PET/CT for the pre-operative localization of foci of over-secreting beta cells in CHI and the discrimination between focal and diffuse CHI. We will compare GLP-1R PET/CT to the currently used pre-operative imaging technique (18F-DOPA PET combined with contrast enhanced CT). To compare these imaging techniques according to sensitivity, we will analyze intra-operative findings and clinical outcomes.
These highly relevant data will allow us to evaluate the expression of GLP-1R in CHI and its usefulness as a target for diagnosis of this disease. Since the localization of foci in CHI and the discrimination between focal and diffuse CHI is challenging, surgical removal of unnecessary large portions of the pancreas in frequently necessary. Evaluation of a better target for pre-operative imaging would therefore be of great value.
Objective:
The primary objective is the in vivo and ex vivo investigation of the expression and distribution of the GLP-1R in the pancreas of CHI patients. A 68Ga-NODAGA-exendin 4 PET/CT will be performed in all patients included in this study. The results of quantitative imaging will then be compared to GLP-1R expression and autoradiography of surgical specimens to determine the interdependency of radiotracer uptake, beta cell mass and GLP-1R expression.
Furthermore, GLP-1R imaging will be compared to the standard imaging techniques now used in pre-operative imaging of children with CHI. All patients will undergo the standard imaging procedure, consisting of an 18F-DOPA PET scan combined with a contrast-enhanced CT. The results of the GLP-1R imaging will be compared to standard imaging in respect to sensitivity for localization of the lesion and discrimination between focal and diffuse CHI. This will be determined by the comparison of the results of pre-operative imaging with intra-operative findings.
Also, the safety (side-effects) of 68Ga-NODAGA-exendin and 18F-DOPA will be assessed.
Furthermore, dosimetric calculations will be performed and the minimum radioactivity dose of 68Ga-NODAGA-exendin 4 to obtain acceptable/reliable images will be determined.
- Conditions
- Congenital Hyperinsulinism
- Being tested
- 68Ga-exendin-4 PET/CT
- Keywords
- Exendin, GLP-1, PET/CT
- Medical subject headings
- Congenital Hyperinsulinism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
68Ga-exendin-4 PET/CTDiagnostic test
68Ga-exendin-4 PET/CT
What is being measured
The primary outcome is the main question the study is designed to answer.
Expression and distribution of GLP-1R in pancreas of children with CHI
Comparison of PET quantification with autoradiography and histology
Measured: 1 year
Secondary outcomes (1)
Comparison of the exendin PET/CT and F-DOPA PET/CT
Comparison of sensitivity and specificity for localization of focal CHI
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2018
- Study start7 Feb 2018
- Primary completion1 Feb 2019 (estimated)
- Study completion1 Feb 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Congenital HyperinsulinismStudies 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- European Commission, University College, London, Charite University, Berlin, Germany, University Hospital, Basel, Switzerland, Insel Gruppe AG, University Hospital Bern, University of Helsinki, Turku University Hospital, University Medical Center Groningen
- Responsible party
- Principal investigator, Martin Gotthardt, Radboud University Medical Center
- Investigators
- Martin Gotthardt, Prof., Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03768518
- Sponsor's protocol ID
- NL54275.091.15
- Acronym
- GLP-1-CHI
- Status last verified
- Dec 2018
- First submitted
- 11 Jul 2018
- Last updated
- 7 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Physiology of Glucagon-like-peptide-1 Espression in Patients With Endogenous Hyperinsulinism: Correlation With Histopathology
- ClinicalTrials.gov ID
- NCT03768518
- Acronym / sponsor ID
- GLP-1-CHI / NL54275.091.15
- Conditions
- Congenital Hyperinsulinism
- Keywords
- Exendin, GLP-1, PET/CT
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- European Commission, University College, London, Charite University, Berlin, Germany, University Hospital, Basel, Switzerland, Insel Gruppe AG, University Hospital Bern, University of Helsinki, Turku University Hospital, University Medical Center Groningen
- Study start
- 7 Feb 2018 (actual)
- Primary completion
- 1 Feb 2019 (estimated)
- Study completion
- 1 Feb 2019 (estimated)
- First posted
- 7 Dec 2018 (actual)
- 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.
The primary objective is the in vivo and ex vivo investigation of the expression and distribution of the GLP-1R in the pancreas of CHI patients.
Detailed description
Congenital hyperinsulinism (CHI) is a rare disease of infants characterized by the presence of functionally defective non-neoplastic beta-cells with inappropriate (over-) secretion of insulin, leading to life-threatening hypoglycaemia. Beta cells specifically express the glucagon-like-peptide-1 (GLP-1R), which could be a promising target for diagnostic and therapeutic purposes. In this study we propose to investigate the physiology of GLP-1 receptor expression in CHI. Expression of the GLP-1 receptor will be quantified in vivo by 68Ga-NODAGA-exendin-4 PET/CT. This data will be compared with post-surgical autoradiography and morphometric determinations.
Furthermore, we will evaluate 68Ga-exendin-4 PET/CT for the pre-operative localization of foci of over-secreting beta cells in CHI and the discrimination between focal and diffuse CHI. We will compare GLP-1R PET/CT to the currently used pre-operative imaging technique (18F-DOPA PET combined with contrast enhanced CT). To compare these imaging techniques according to sensitivity, we will analyze intra-operative findings and clinical outcomes.
These highly relevant data will allow us to evaluate the expression of GLP-1R in CHI and its usefulness as a target for diagnosis of this disease. Since the localization of foci in CHI and the discrimination between focal and diffuse CHI is challenging, surgical removal of unnecessary large portions of the pancreas in frequently necessary. Evaluation of a better target for pre-operative imaging would therefore be of great value.
Objective:
The primary objective is the in vivo and ex vivo investigation of the expression and distribution of the GLP-1R in the pancreas of CHI patients. A 68Ga-NODAGA-exendin 4 PET/CT will be performed in all patients included in this study. The results of quantitative imaging will then be compared to GLP-1R expression and autoradiography of surgical specimens to determine the interdependency of radiotracer uptake, beta cell mass and GLP-1R expression.
Furthermore, GLP-1R imaging will be compared to the standard imaging techniques now used in pre-operative imaging of children with CHI. All patients will undergo the standard imaging procedure, consisting of an 18F-DOPA PET scan combined with a contrast-enhanced CT. The results of the GLP-1R imaging will be compared to standard imaging in respect to sensitivity for localization of the lesion and discrimination between focal and diffuse CHI. This will be determined by the comparison of the results of pre-operative imaging with intra-operative findings.
Also, the safety (side-effects) of 68Ga-NODAGA-exendin and 18F-DOPA will be assessed.
Furthermore, dosimetric calculations will be performed and the minimum radioactivity dose of 68Ga-NODAGA-exendin 4 to obtain acceptable/reliable images will be determined.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- Up to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- patients (<16 years) with biochemically proven endogenous congenital hyperinsulinism
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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
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 |
|---|---|---|
| 68Ga-exendin-4 PET/CT68Ga-exendin-4 PET/CT | Diagnostic test | – |
Primary outcome
Expression and distribution of GLP-1R in pancreas of children with CHI
Time frame: 1 year
Comparison of PET quantification with autoradiography and histology
1 secondary outcome
Comparison of the exendin PET/CT and F-DOPA PET/CT
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2018.
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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.
Martin Gotthardt, Prof. principal investigator
Radboud University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Congenital Hyperinsulinism, run by Radboud University Medical Center at 1 site in Netherlands.
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 6 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 7 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marti Boss (+31243667243, marti.boss@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Expression and distribution of GLP-1R in pancreas of children with CHI (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Dec 2018.