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

Type 1 Diabetes Clinical Trial

— GIPHYPO  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06137586
• Other study ID #: GIPHYPO2022
• Status: Recruiting
• Phase: N/A
• Start date: August 10, 2022
• Est. completion date: December 1, 2024

Study information

• Verified date: November 2023
• Source: University Hospital, Gentofte, Copenhagen
• Contact: Asger B Lund, MD
• Phone: +4561676558
• Email: Asger.Lund.01[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: December 1, 2024
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Hypoglycemia
• Type 1 Diabetes
• Type1diabetes

Intervention

Other:
• 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)

Locations

Country	Name	City	State
Denmark	Center for Clinical Metabolic Research, Gentofte Hospital	Hellerup	Copenhagen

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Gentofte, Copenhagen	The Novo Nordisk Foundation Center for Basic Metabolic Research

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Glucagon response during insulin infusion	Difference in bsAUC for glucagon between study days with GIP[1-42], GIP[1-30] and placebo, respectively during the insulin infusion	30-90minutes
Secondary	Glucagon response after blood glucose (BG) falls below 3.0 mmol/L	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	t[BG<3.0] and the following 30 minutes
Secondary	Glucagon response during recovery	Difference in bsAUC for glucagon between study days with GIP[1-42], GIP[1-30] and placebo, respectively during the recovery period	90-135minutes
Secondary	Total insulin response	Difference in plasma levels of insulin between study days with GIP[1-42], GIP[1-30] and placebo, respectively	0-135minutes
Secondary	Total c-peptide response	Difference in plasma levels of c-peptide between study days with GIP[1-42], GIP[1-30] and placebo, respectively	0-135minutes
Secondary	Amount of glucose infused	Difference in infusion rates for glucose between study days with GIP[1-42], GIP[1-30] and placebo, respectively	0-135minutes
Secondary	Difference in epinephrine	Difference in plasma levels of epinephrine between study days with GIP[1-42], GIP[1-30] and placebo, respectively	0-135minutes
Secondary	Difference in norepinephrine	Difference in plasma levels of norepinephrine between study days with GIP[1-42], GIP[1-30] and placebo, respectively	0-135minutes
Secondary	Difference in cortisol	Difference in plasma levels of cortisol between study days with GIP[1-42], GIP[1-30] and placebo, respectively	0-135minutes
Secondary	Difference in growth hormone hormones	Difference in plasma levels of growth hormone between study days with GIP[1-42], GIP[1-30] and placebo, respectively	0-135minutes
Secondary	Difference in Procollagen 1 Intact N-Terminal Propeptide (P1NP)	Difference in plasma levels of P1NP between study days with GIP[1-42], GIP[1-30] and placebo, respectively	0-135minutes
Secondary	Difference in carboxy-terminal collagen crosslinks (CTX)	Difference in plasma levels of CTX between study days with GIP[1-42], GIP[1-30] and placebo, respectively	0-135minutes
Secondary	Difference in blood pressure	Difference in blood pressure between study days with GIP[1-42], GIP[1-30] and placebo, respectively	0-135minutes
Secondary	Difference in heart rate	Difference in heart rate between study days with GIP[1-42], GIP[1-30] and placebo, respectively	0-135minutes