Effect of Gelofusine on GLP1-receptor Imaging

NCT ID: NCT02541734

Last Updated: 2017-05-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2017-05-31

Brief 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. 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.

Conditions

Diabetes Mellitus, Non-Insulin-Dependent; Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

gelofusine and 111In-exendin 4 SPECT/CT

subjects will receive a gelofusine injection before the injection of the radiopharmaceutical (111In-exendin 4)

Group Type: EXPERIMENTAL

Gelofusine

Intervention Type: DRUG

Infusion of gelofusine

111In-exendin 4 SPECT/CT

Intervention Type: RADIATION

111In-exendin 4 SPECT/CT

saline and 111In-exendin 4 SPECT/CT

As a control, subjects will receive an injection of saline before the injection of the radiopharmaceutical (111In-exendin 4)

Group Type: PLACEBO_COMPARATOR

111In-exendin 4 SPECT/CT

Intervention Type: RADIATION

111In-exendin 4 SPECT/CT

Placebo

Intervention Type: DRUG

Interventions

Gelofusine

Infusion of gelofusine

Intervention Type: DRUG

111In-exendin 4 SPECT/CT

111In-exendin 4 SPECT/CT

Intervention Type: RADIATION

Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• >= 18 years
• <= 60 years
• Normal renal function
• Normal glucose regulation
• BMI 17>30

Exclusion Criteria

• Use of any medication affecting renal function
• Known hypersensitivity to one of the substances used
• Hypertension
• Oedema
• Hypervolaemia
• Heart failure
• 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Martin Gotthardt, Prof Dr

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Other Identifiers

2014-003006-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NL50233.091.14

Identifier Type: -

Identifier Source: org_study_id