Effect of Gelofusine on GLP1-receptor Imaging (GLP1-EX-GELO)

May 29, 2017 updated by: Radboud University Medical Center

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 2
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: gelofusine and 111In-exendin 4 SPECT/CT
subjects will receive a gelofusine injection before the injection of the radiopharmaceutical (111In-exendin 4)
Drug: Gelofusine
Infusion of gelofusine
Radiation: 111In-exendin 4 SPECT/CT
111In-exendin 4 SPECT/CT
Placebo Comparator: 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)
Drug: Placebo
Radiation: 111In-exendin 4 SPECT/CT
111In-exendin 4 SPECT/CT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
up to 8 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Pancreas uptake as measured by uptake of 111In-exendin-4 on SPECT images
Time Frame: up to 8 months
up to 8 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Investigators

  • Principal Investigator: Martin Gotthardt, Prof Dr, Radboud University Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2015

Primary Completion (Actual)

May 1, 2017

Study Completion (Actual)

May 1, 2017

Study Registration Dates

First Submitted

March 3, 2015

First Submitted That Met QC Criteria

September 3, 2015

First Posted (Estimate)

September 4, 2015

Study Record Updates

Last Update Posted (Actual)

May 31, 2017

Last Update Submitted That Met QC Criteria

May 29, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL50233.091.14
  • 2014-003006-33 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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