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Completed

NCT Number: NCT06137586

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

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.

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Key information

Conditions

Type1diabetes Autoimmune Diseases Diabetes Mellitus Diabetes Mellitus, Type 1 Endocrine System Diseases Glucose Metabolism Disorders Hypoglycemia Immune System Diseases Metabolic Diseases Nutritional and Metabolic Diseases Type 1 Diabetes

Age range

18 year–70 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

Center for Clinical Metabolic Research, Gentofte Hospital

Hellerup, Copenhagen, 2900, Denmark

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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)

Primary outcomes

  1. Total glucagon response

    Time frame: 0-135minutes

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

Secondary outcomes

  1. Glucagon response during insulin infusion

    Time frame: 30-90minutes

    Difference in bsAUC for glucagon between study days with GIP[1-42], GIP[1-30] and placebo, respectively during the insulin infusion

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

    Time frame: t[BG<3.0] and the following 30 minutes

    Difference in bsAUC for glucagon between study days with GIP[1-42], GIP[1-30] and placebo, respectively in the 30 minutes following a blood glucose of below 3.0 mmol/L

  3. Glucagon response during recovery

    Time frame: 90-135minutes

    Difference in bsAUC for glucagon between study days with GIP[1-42], GIP[1-30] and placebo, respectively during the recovery period

  4. Total insulin response

    Time frame: 0-135minutes

    Difference in plasma levels of insulin between study days with GIP[1-42], GIP[1-30] and placebo, respectively

  5. Total c-peptide response

    Time frame: 0-135minutes

    Difference in plasma levels of c-peptide between study days with GIP[1-42], GIP[1-30] and placebo, respectively

  6. Amount of glucose infused

    Time frame: 0-135minutes

    Difference in infusion rates for glucose between study days with GIP[1-42], GIP[1-30] and placebo, respectively

  7. Difference in epinephrine

    Time frame: 0-135minutes

    Difference in plasma levels of epinephrine between study days with GIP[1-42], GIP[1-30] and placebo, respectively

  8. Difference in norepinephrine

    Time frame: 0-135minutes

    Difference in plasma levels of norepinephrine between study days with GIP[1-42], GIP[1-30] and placebo, respectively

  9. Difference in cortisol

    Time frame: 0-135minutes

    Difference in plasma levels of cortisol between study days with GIP[1-42], GIP[1-30] and placebo, respectively

  10. Difference in growth hormone hormones

    Time frame: 0-135minutes

    Difference in plasma levels of growth hormone between study days with GIP[1-42], GIP[1-30] and placebo, respectively

  11. Difference in Procollagen 1 Intact N-Terminal Propeptide (P1NP)

    Time frame: 0-135minutes

    Difference in plasma levels of P1NP between study days with GIP[1-42], GIP[1-30] and placebo, respectively

  12. Difference in carboxy-terminal collagen crosslinks (CTX)

    Time frame: 0-135minutes

    Difference in plasma levels of CTX between study days with GIP[1-42], GIP[1-30] and placebo, respectively

  13. Difference in blood pressure

    Time frame: 0-135minutes

    Difference in blood pressure between study days with GIP[1-42], GIP[1-30] and placebo, respectively

  14. Difference in heart rate

    Time frame: 0-135minutes

    Difference in heart rate between study days with GIP[1-42], GIP[1-30] and placebo, respectively

Sponsors and collaborators

Lead sponsor

University Hospital, Gentofte, Copenhagen

Other

Collaborators

  • The Novo Nordisk Foundation Center for Basic Metabolic Research

Registry information

Acronym: GIPHYPO

Important dates

Study start
2022
Primary completion
2024
Study completion
2024
First posted
Nov 18, 2023
Registry last updated
Dec 10, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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