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

NCT06137586 | Completed DMC

• 1 other identifier: GIPHYPO2022
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Type1diabetes; Hypoglycemia; Type 1 Diabetes

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Total glucagon response

  Difference in baseline subtracted area under the curve (bsAUC) for glucagon between study days with GIP\[1-42\], GIP\[1-30\] and placebo, respectively

  0-135minutes

Secondary Outcomes (14)

• Glucagon response during insulin infusion

  30-90minutes

• Glucagon response after blood glucose (BG) falls below 3.0 mmol/L

  t[BG<3.0] and the following 30 minutes

• Glucagon response during recovery

  90-135minutes

• Total insulin response

  0-135minutes

• Total c-peptide response

  0-135minutes

Study Arms (1)

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

EXPERIMENTAL

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)

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

Interventions

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

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

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Gentofte, Copenhagen: lead
• The Novo Nordisk Foundation Center for Basic Metabolic Research: collaborator

Study Sites (1)

Center for Clinical Metabolic Research, Gentofte Hospital

Hellerup, Copenhagen, 2900, Denmark

Location

MeSH Terms

Conditions

Hypoglycemia; Diabetes Mellitus, Type 1

Interventions

gastric inhibitory polypeptide (1-30)

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: The randomized order of infusions is blinded to both participant and investigator
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator, MD, ph.d.

Model Details: Randomized, double-blinded, single-arm study. Each participant goes through five experimental days in a randomized order - acting as their own controls

Study Record Dates

• First Submitted: November 9, 2023
• First Posted: November 18, 2023
• Study Start: August 10, 2022
• Primary Completion: May 17, 2024
• Study Completion: May 17, 2024
• Last Updated: December 10, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share

Locations

DK (1)