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The Glucagonotropic Effects of Glucose-dependent Insulinotropic Polypeptide and Alanine in Healthy Individuals

Phase 1
Recruiting
Conditions
Effect of iv Administration of GIP and Alanine
Interventions
Other: Placebo (saline)
Drug: GIP
Registration Number
NCT06419686
Lead Sponsor
University Hospital, Gentofte, Copenhagen
Brief Summary

The study is a randomised, double-blinded, placebo-controlled, crossover study enrolling 10 healthy male participants. Each participant will undergo four separate study days in randomised order. Each study day encompasses a continous 90-minute i.v. infusion with either placebo, glucose-dependent insulinotropic polypeptide (GIP), alanine or GIP + alanine.

The primary objective of the study is to find out whether intravenous administration of the naturally occuring gut hormone GIP and the amino acid alanine, separately and combined, results in additive or synergistic glucagonotropic effects during euglycaemic conditions in healthy participants. Secondary objectives are to disclose the effect of the abovementioned interventions on insulin secretion and circulating levels of total and individual amino acids.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
Male
Target Recruitment
10
Inclusion Criteria
  • Caucasian ethnicity
  • Body mass index (BMI) 20-27 kg/m^2
  • Glycated haemoglobin (HbA1c) ≤ 42 mmol/mol
  • Informed and written consent
Exclusion Criteria
  • Late microvascular complications except mild nonproliferative retinopathy
  • Liver disease (alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) > 2 times normal values) or history of hepatobiliary disorder
  • Treatment with any glucose-lowering drugs
  • Active or recent (within 5 years) malignant disease
  • Active tobacco smoking/use
  • Any condition considered incompatible with participation by the investigators.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
GIP + AlanineGIP + alanineIntravenous administration of GIP and alanine for 90 minutes. GIP is given at a priming dose of 6 pmol/kg/min for 10 minutes and then 4 pmol/kg for 80 minutes. Alanine is given at 28 umol/kg/min for 90 minutes.
SalinePlacebo (saline)Intravenous administration of saline for 90 minutes.
AlanineAlanineIntravenous administration of alanine for 90 minutes (28 umol/kg/min).
GIPGIPIntravenous administration of GIP for 90 minutes (priming dose 6 pmol/kg/min for 10 minutes and 4 pmol/kg for 80 minutes.
Primary Outcome Measures
NameTimeMethod
Plasma concentrations of GlucagonTimepoint -30 to 90 minutes

Baseline-corrected area under the curve (bsAUC)

Secondary Outcome Measures
NameTimeMethod
Serum concentration of C-peptidTimepoint -30 to 90 minutes

Baseline-corrected area under the curve (bsAUC).

Circulating levels of total amino acidsTimepoint -30 to 90 minutes

Baseline-corrected area under the curve (bsAUC).

Circulating levels of P1NPTimepoint -30 to 90 minutes

Baseline-corrected area under the curve (bsAUC).

PulseTimepoint -30, 0, 30, 60, 90

Baseline-corrected area under the curve (bsAUC).

Plasma concentration of GIPTimepoint -30 to 90 minutes

Baseline-corrected area under the curve (bsAUC).

Blood pressureTimepoint -30, 0, 30, 60, 90

Baseline-corrected area under the curve (bsAUC).

Plasma concentration of glucoseTimepoint -30 to 90 minutes

Peak value

Circulating levels of individual amino acidsTimepoint -30 to 90 minutes

Baseline-corrected area under the curve (bsAUC).

Serum concentration of InsulinTimepoint -30 to 90 minutes

Baseline-corrected area under the curve (bsAUC).

Lipid profileTimepoint -30 to 90 minutes

Baseline-corrected area under the curve (bsAUC).

Circulating levels of CTxTimepoint -30 to 90 minutes

Baseline-corrected area under the curve (bsAUC).

Trial Locations

Locations (1)

Center for Clinical Metabolic Research, Gentofte Hospital

🇩🇰

Hellerup, Capital Region, Denmark

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