The Effect of Glucose-dependent Insulinotropic Polypeptide on the Alpha Cell Response to Hypoglycaemia in Patients with Type 1 Diabetes

NCT ID: NCT06137586

Last Updated: 2024-12-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-10
• Study Completion Date: 2024-05-17

Brief Summary

The goal of this clinical trial is to evaluate the effects of the hormone glucose-dependent insulinotropic polypeptide (GIP) and its two isoforms, GIP[1-30] and GIP[1-42], in patients with type 1 diabetes. The main question it aims to answer is:

• What dose and isoform of GIP can most potently stimulate glucagon secretion during low blood sugar in patients with type 1 diabetes?

Participants will go through 5 experimental days that are identical except for an intravenous infusion of either placebo (saline), high or low dose GIP[1-42] or high or low dose GIP[1-30]. On all days, blood sugar will be lowered to around 2.5mmol/l for around 20-30min.

Detailed Description

After being informed about the study and the potential risks, each participant giving written informed consent will participate in five double-blinded experimental days (Day A-E) in a randomized order. Each experimental day is identical except for an intravenous infusion of either placebo (saline), high (8pmol/kg/min) or low (4pmol/kg/min) dose GIP[1-42] or high (8pmol/kg/min) or low (4pmol/kg/min) dose GIP[1-30].

Each experimental day will consist of an induction period where the participant's blood sugar is adjusted to around 5-6mmol/l with either insulin or glucose. Then the infusion of either placebo or hormone will be initiated and continued for 135 minutes.

After 30 minutes of hormone infusion, a separate infusion of insulin (1.5mU/kg/min) will be initiated and continued for 60 minutes. Based on frequent bed-side plasma glucose measurements and an adjustable 20% glucose infusion, plasma glucose will be clamped at 2.5 mmol/l until the insulin infusion is terminated. Following this is a 45 minute recovery period, during which a minimum of glucose is infused, to ensure a steady rise from 2.5mmol/l to 3.5mmol/l.

After the study day, patients will receive a meal to prevent subsequent hypoglycemia.

The effects of each infusion will be evaluated with regards to glucagonotropic potency, as well as a series of exploratory outcomes.

Conditions

Type1diabetes; Hypoglycemia; Type 1 Diabetes

Keywords

Incretins; GIP; Glucose-dependent insulinotropic polypeptide; Alpha cell

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Infusion of GIP[1-42], GIP[1-30] or placebo

This is a single arm study. All participants will go through all five experimental days in a randomized order. The interventions are A) 4pmol/kg/min GIP\[1-42\] B) 8pmol/kg/min GIP\[1-42\] C) 4pmol/kg/min GIP\[1-30\] D) 8pmol/kg/min GIP\[1-30\] E) Saline (placebo)

Group Type: EXPERIMENTAL

Infusion of GIP[1-42], GIP[1-30] or placebo

Intervention Type: OTHER

This is a single arm study. All participants will go through all five experimental days in a randomized order. The interventions are A) 4pmol/kg/min GIP\[1-42\] B) 8pmol/kg/min GIP\[1-42\] C) 4pmol/kg/min GIP\[1-30\] D) 8pmol/kg/min GIP\[1-30\] E) Saline (placebo)

Interventions

Infusion of GIP[1-42], GIP[1-30] or placebo

This is a single arm study. All participants will go through all five experimental days in a randomized order. The interventions are A) 4pmol/kg/min GIP\[1-42\] B) 8pmol/kg/min GIP\[1-42\] C) 4pmol/kg/min GIP\[1-30\] D) 8pmol/kg/min GIP\[1-30\] E) Saline (placebo)

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Caucasian men
• Body mass index between 18-27kg/m2
• Type 1 diabetes (T1D) (diagnosed according to the criteria of the World Health Organization) with HbA1c<69 mmol/mol (<8.5%)
• T1D duration of 2-30 years
• C-peptide negative (stimulated C-peptide ≤ 100 pmol/l)
• Treatment with a stable basal-bolus or insulin pump regimen for ≥3 months
• Informed consent

Exclusion Criteria

• Anaemia (haemoglobin below normal range)
• Liver disease (ALAT and/or ASAT >2 times normal values) or history of hepatobiliary disorder
• Late microvascular complications except mild nonproliferative retinopathy
• Allergy or intolerance to ingredients included in the standardized meals
• Prior myocardial infarction or other cardiac events
• Any physical or psychological condition that the investigator feels would interfere with trial participation
• Treatment with any glucose-lowering drugs beside insulin

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

The Novo Nordisk Foundation Center for Basic Metabolic Research

OTHER

Sponsor Role: collaborator

University Hospital, Gentofte, Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Asger Lund, MD

Principal investigator, MD, ph.d.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Center for Clinical Metabolic Research, Gentofte Hospital

Hellerup, Copenhagen, Denmark

Countries

Denmark

Other Identifiers

GIPHYPO2022

Identifier Type: -

Identifier Source: org_study_id