Diabetes Mellitus, Non-Insulin-DependentPhase 1/2GLP1-EX-GELONCT02541734
Effect of Gelofusine on GLP1-receptor Imaging
A Phase 1/2 study testing Gelofusine and 111In-exendin 4 SPECT/CT in people with Diabetes Mellitus, Non-Insulin-Dependent and Diabetes Mellitus, run by Radboud University Medical Center.
Trial summary
The highly promising and innovative tracer on 111In-DTPA-AHX-Lys40-Exendin 4 has been applied to determine beta cell mass in healthy volunteers and patients with type 1 diabetes. However, the high retention of the tracer in the kidneys was leading to a kidney/pancreas uptake ratio of 41±23. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Non-Insulin-Dependent, Diabetes Mellitus
- What is being tested?
- Gelofusine and 111In-exendin 4 SPECT/CT
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- No sites listed yet
- Study dates
- Aug 2015to May 2017
- Phase
- Phase 1/2
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- >= 18 years
- <= 60 years
- Normal renal function
- Normal glucose regulation
- BMI 17>30
Who cannot join
- Use of any medication affecting renal function
- Known hypersensitivity to one of the substances used
- Hypertension
- Oedema
- Hypervolaemia
- Heart failure
Show all 10Show fewer
- Pregnancy or the wish to become pregnant within 3 months after participation of the study.
- Lactation
- History of anaphylaxis
- Liver disease defined as aspartate aminotransferase or alanine aminotransferase level more than 3 times the upper limit of normal range (45U/L)
About this study
Official title: Effect of Gelofusine on 111In-DTPA-AHX-Lys40-Exendin 4 Uptake in the Kidney
The highly promising and innovative tracer on 111In-DTPA-AHX-Lys40-Exendin 4 has been applied to determine beta cell mass in healthy volunteers and patients with type 1 diabetes. However, the high retention of the tracer in the kidneys was leading to a kidney/pancreas uptake ratio of 41±23. This high renal uptake is complicating absolute BCM quantification by SPECT imaging. In order to reduce the kidney/pancreas uptake ratio, investigators propose a co-infusion with the plasma expander Gelofusine since it has been shown in several pre-clinical and clinical studies that Gelofusine can reduce the renal retention of several other, closely related tracers. When investigators are able to reduce the kidney/pancreas uptake ratio, these findings will improve the interpretation of clinical quantitative SPECT, having important implications for therapeutic decision making for patients with diabetes, insulinomas or congenital hyperinsulinism, and may also have a major impact on our understanding of the pathophysiology of these diseases.
Read the detailed description
Beta-cell imaging in vivo
Reliable, sensitive and specific non-invasive methods for comprehensive structural and functional characterization of living pancreatic beta-cells in vivo (and in vitro) would not only enhance our understanding of the pathophysiology of various diseases, but also enable longitudinal in vivo assessment of beta cell mass (BCM) and distribution in patients with e.g. diabetes (including patients who received beta cell replacement therapy). Additionally, it can help in diagnosing insulinomas and congenital hyperinsulinism and when coupled to other biomarkers it could aid patient stratification and enable patient-specific optimized treatment strategies.
Inhibiting the reabsorption of radiolabelled peptides
It has been shown, both in vitro and in vivo, that the kidney uptake of radiolabelled peptides can be reduced by co-infusion of agents that inhibit the reabsorption of these peptides. One of these agents is succinylated gelatin (Gelofusine), a plasma expander that consists of a mixture of collagen-derived peptides. Previous clinical observations have shown that Gelofusine infusion results in tubular proteinuria of both albumin and β2-microglobulin. Although the exact mechanism for this proteinuria is not completely understood, the megalin receptor system is most likely involved. Based on pre-clinical studies in mice and rats, it has been known that kidney uptake is significantly reduced for various tracers when co-infused with Gelofusine, like 111In-Octreotide 111In-Minigastrin, 68Ga-exendin-4 and 111In-DTPA-AHX-Lys40-Exendin 4. Additionally, it was shown that Gelofusine also reduces the renal retention of 111In- Octreotide by 45% in humans. In the current study, investigators will determine whether Gelofusine has also an effect on kidney retention of 111In-DTPA-AHX-Lys40-Exendin 4 in humans.
- Being tested
- Gelofusine, 111In-exendin 4 SPECT/CT, Placebo
- Keywords
- SPECT, radiopeptides, gelofusine, Beta cell
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GelofusineDrug
Infusion of gelofusine
111In-exendin 4 SPECT/CTRadiation
111In-exendin 4 SPECT/CT
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| gelofusine and 111In-exendin 4 SPECT/CT | Experimental | subjects will receive a gelofusine injection before the injection of the radiopharmaceutical (111In-exendin 4) Receives: Drug: Gelofusine; Radiation: 111In-exendin 4 SPECT/CT |
| saline and 111In-exendin 4 SPECT/CT | Placebo comparator | As a control, subjects will receive an injection of saline before the injection of the radiopharmaceutical (111In-exendin 4) Receives: Radiation: 111In-exendin 4 SPECT/CT; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Renal uptake as measured by uptake of 111In-exendin-4 on SPECT images and without co-infusion of Gelofusine.
Measured: up to 8 months
Secondary outcomes (1)
Pancreas uptake as measured by uptake of 111In-exendin-4 on SPECT images
Measured: up to 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2015 (estimated)
- Study startAug 2015
- Primary completionMay 2017
- Study completionMay 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Non-Insulin-DependentStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Martin Gotthardt, Prof Dr, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02541734
- Sponsor's protocol ID
- NL50233.091.14
- Other IDs
- 2014-003006-33, 2014
- Acronym
- GLP1-EX-GELO
- Status last verified
- May 2017
- First submitted
- 3 Mar 2015
- Last updated
- 31 May 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Gelofusine on 111In-DTPA-AHX-Lys40-Exendin 4 Uptake in the Kidney
- ClinicalTrials.gov ID
- NCT02541734
- Acronym / sponsor ID
- GLP1-EX-GELO / NL50233.091.14
- Keywords
- SPECT, radiopeptides, gelofusine, Beta cell
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Aug 2015
- Primary completion
- May 2017 (actual)
- Study completion
- May 2017 (actual)
- First posted
- 4 Sep 2015 (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.
The highly promising and innovative tracer on 111In-DTPA-AHX-Lys40-Exendin 4 has been applied to determine beta cell mass in healthy volunteers and patients with type 1 diabetes. However, the high retention of the tracer in the kidneys was leading to a kidney/pancreas uptake ratio of 41±23. This high renal uptake is complicating absolute BCM quantification by SPECT imaging. In order to reduce the kidney/pancreas uptake ratio, investigators propose a co-infusion with the plasma expander Gelofusine since it has been shown in several pre-clinical and clinical studies that Gelofusine can reduce the renal retention of several other, closely related tracers. When investigators are able to reduce the kidney/pancreas uptake ratio, these findings will improve the interpretation of clinical quantitative SPECT, having important implications for therapeutic decision making for patients with diabetes, insulinomas or congenital hyperinsulinism, and may also have a major impact on our understanding of the pathophysiology of these diseases.
Detailed description
Beta-cell imaging in vivo
Reliable, sensitive and specific non-invasive methods for comprehensive structural and functional characterization of living pancreatic beta-cells in vivo (and in vitro) would not only enhance our understanding of the pathophysiology of various diseases, but also enable longitudinal in vivo assessment of beta cell mass (BCM) and distribution in patients with e.g. diabetes (including patients who received beta cell replacement therapy). Additionally, it can help in diagnosing insulinomas and congenital hyperinsulinism and when coupled to other biomarkers it could aid patient stratification and enable patient-specific optimized treatment strategies.
Inhibiting the reabsorption of radiolabelled peptides
It has been shown, both in vitro and in vivo, that the kidney uptake of radiolabelled peptides can be reduced by co-infusion of agents that inhibit the reabsorption of these peptides. One of these agents is succinylated gelatin (Gelofusine), a plasma expander that consists of a mixture of collagen-derived peptides. Previous clinical observations have shown that Gelofusine infusion results in tubular proteinuria of both albumin and β2-microglobulin. Although the exact mechanism for this proteinuria is not completely understood, the megalin receptor system is most likely involved. Based on pre-clinical studies in mice and rats, it has been known that kidney uptake is significantly reduced for various tracers when co-infused with Gelofusine, like 111In-Octreotide 111In-Minigastrin, 68Ga-exendin-4 and 111In-DTPA-AHX-Lys40-Exendin 4. Additionally, it was shown that Gelofusine also reduces the renal retention of 111In- Octreotide by 45% in humans. In the current study, investigators will determine whether Gelofusine has also an effect on kidney retention of 111In-DTPA-AHX-Lys40-Exendin 4 in humans.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| gelofusine and 111In-exendin 4 SPECT/CT | Experimental | Drug: Gelofusine, Radiation: 111In-exendin 4 SPECT/CTsubjects will receive a gelofusine injection before the injection of the radiopharmaceutical (111In-exendin 4) |
| saline and 111In-exendin 4 SPECT/CT | Placebo comparator | Radiation: 111In-exendin 4 SPECT/CT, Drug: PlaceboAs a control, subjects will receive an injection of saline before the injection of the radiopharmaceutical (111In-exendin 4) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- >= 18 years
- <= 60 years
- Normal renal function
- Normal glucose regulation
- BMI 17>30
Key exclusion criteria (10 listed)
- Use of any medication affecting renal function
- Known hypersensitivity to one of the substances used
- Hypertension
- Oedema
- Hypervolaemia
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 |
|---|---|---|
| GelofusineInfusion of gelofusine | Drug | gelofusine and 111In-exendin 4 SPECT/CT |
| 111In-exendin 4 SPECT/CT111In-exendin 4 SPECT/CT | Radiation | gelofusine and 111In-exendin 4 SPECT/CT, saline and 111In-exendin 4 SPECT/CT |
| Placebo | Drug | saline and 111In-exendin 4 SPECT/CT |
Primary outcome
Renal uptake as measured by uptake of 111In-exendin-4 on SPECT images and without co-infusion of Gelofusine.
Time frame: up to 8 months
1 secondary outcome
Pancreas uptake as measured by uptake of 111In-exendin-4 on SPECT images
Time frame: up to 8 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2017.
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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 Dr principal investigator
Radboud University Medical Center
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Gelofusine and 111In-exendin 4 SPECT/CT in people with Diabetes Mellitus, Non-Insulin-Dependent and Diabetes Mellitus, run by Radboud University Medical Center.
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 10 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: finished, as of the sponsor's last update on 31 May 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Renal uptake as measured by uptake of 111In-exendin-4 on SPECT images and without co-infusion of Gelofusine. (time frame: up to 8 months). 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 31 May 2017.