Beta Cell Imaging in T1D Patients With a Different Glycemic Control (GLP1-reg)

Beta Cell Imaging in Type 1 Diabetes With Stable Near-normal and Unstable Glucose Control Using PET

The primary aim of this study is to measure (residual) beta cell mass in type 1 diabetes (T1D) patients with stable near-normal and unstable glucose control using PET/CT imaging, to improve the understanding of the relation between beta cell mass and glycemic control in T1D.

Study Overview

• Status: Terminated
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Radiation: gallium-68-exendin PET/CT

Detailed Description

Type 1 diabetes (T1D) is characterized by a progressive decrease in beta cell function due to an autoimmune attack on the beta cells, which will lead to a reduction in insulin secretion. Endogenous insulin secretion can be determined measuring C-peptide, which is secreted in equal amounts to insulin. The loss of insulin secretion, indicated by an immeasurable C-peptide level, will hamper glycemic control which results in increased glycated haemoglobin (HbA1c) levels. Also, hypoglycemic events can occur more frequently. Initially, the belief was that this could be explained by the loss of all pancreatic beta cells due to the autoimmune attack. However, recent literature suggests that a considerable number of beta cells can survive this attack. This could mean that certain beta cells survived, but have lost their function. The ratio of functional and non-functional residual beta cells might play an important role in the degree of glycemic control. It would therefore be of great interest to study residual beta cell mass in two types of T1D patients that differ in glycemic control. Although both types of patients receive treatment, one group of patients is characterized by a stable near-normal glucose control while the second group is characterized by an unstable glucose control. In case glycemic control mostly depends on beta cell function and less on beta cell mass, novel therapies could focus on the functional reactivation of these non-functional beta cells to restore overall beta cell function. This could especially be in favour of patients with an unstable glucose control. Beta cell mass will be determined using Ga-68-NODAGA-exendin-4 positron emission tomography (PET), which allows visualization of pancreatic beta cells as well as absolute quantification of tracer uptake, providing a measure for the pancreatic beta cell mass. The outcome of this study will lead to a better understanding of the relation between the amount of residual beta cells, beta cell function and the influence of glycemic control. This could provide new insights regarding the development of new therapies to improve beta cell function and glycemic control, which could lower disease burden and improve the patient's quality of life.

• Study Type: Observational
• Enrollment (Actual): 16

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Radboudumc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population will include 18 individuals with T1D for at least 1 year with a minimum age of 18 years. This population consists of two groups that include 9 subjects with stable near-normal glucose control and 9 individuals with unstable glucose control. The differentiation between T1D patients with stable near-normal and unstable glucose control will be based on their HbA1c value, the number of severe hypoglycemic events and the patient's hypoglycaemic awareness.

Description

Inclusion Criteria:

Group 1 (stable glycemic control)

• Age ≥18 years
• T1D diagnosed ≥1 year at the start of the study
• HbA1c <7 (<53 mmol/mol)
• 17≤ BMI ≤30 kg/m2
• No severe hypoglycemic events in the past year and a maximum of 2 severe hypoglycemic events in their entire life.
• Intact hypoglycemic awareness
• Ability to sign informed consent

Group 2 (unstable glycemic control) Age ≥18 years

• T1D diagnosed ≥1 year at the start of the study
• HbA1c >8.5 (>69 mmol/mol)
• 17≤ BMI ≤30 kg/m2
• Minimum of 2 severe hypoglycemic events in the past year, or an impaired awareness of hypoglycemia (subjects may comply with both criteria, but this is not a requirement)
• Ability to sign informed consent

Exclusion Criteria:

• Previous treatment (within 6 months) with synthetic Exendin (Exenatide, Byetta®) or Dipeptidyl-Peptidase IV inhibitors
• Liver disease
• Renal disease
• Pregnancy or the wish to become pregnant within 6 months after the study
• Breastfeeding
• BMI <17 kg/m2 or BMI >30 kg/m2
• Age <18 years
• Inability to sign informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Subjects with stable near-normal T1D; Mixed-meal tolerance test; Intravenous injection with gallium-68-exendin followed by a PET/CT scan	Radiation: gallium-68-exendin PET/CT; PET/CT scan after injection with gallium-68-exendin
Subjects with unstable T1D; Mixed-meal tolerance test; Intravenous injection with gallium-68-exendin followed by a PET/CT scan	Radiation: gallium-68-exendin PET/CT; PET/CT scan after injection with gallium-68-exendin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beta cell mass	Pancreatic uptake of the tracer is measured by quantitative analysis (measure for beta cell mass)	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beta cell mass vs. beta cell function	The correlation of the measured beta cell mass to the beta cell function	2 years

Collaborators and Investigators

• Sponsor: Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2017
• Primary Completion (Actual): November 9, 2020
• Study Completion (Actual): November 9, 2020

Study Registration Dates

• First Submitted: December 20, 2018
• First Submitted That Met QC Criteria: December 21, 2018
• First Posted (Actual): December 24, 2018

Study Record Updates

• Last Update Posted (Actual): February 14, 2022
• Last Update Submitted That Met QC Criteria: January 29, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Glycemic control
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: NL59582.091.17

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No