Beta Cell Imaging in T1D Patients With a Different Glycemic Control

NCT ID: NCT03785275

Last Updated: 2022-02-14

Basic Information

• Recruitment Status: TERMINATED
• Total Enrollment: 16 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-12-06
• Study Completion Date: 2020-11-09

Brief Summary

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.

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.

Conditions

Type 1 Diabetes Mellitus

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Subjects with stable near-normal T1D

• Mixed-meal tolerance test
• Intravenous injection with gallium-68-exendin followed by a PET/CT scan

gallium-68-exendin PET/CT

Intervention Type: RADIATION

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

gallium-68-exendin PET/CT

Intervention Type: RADIATION

PET/CT scan after injection with gallium-68-exendin

Interventions

gallium-68-exendin PET/CT

PET/CT scan after injection with gallium-68-exendin

Intervention Type: RADIATION

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Radboudumc

Nijmegen, Gelderland, Netherlands

Countries

Netherlands

Other Identifiers

NL59582.091.17

Identifier Type: -

Identifier Source: org_study_id