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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Effect of iv Administration of GIP and Alanine
• Intervention / Treatment: Other: Placebo (saline); Drug: GIP; Drug: Alanine; Drug: GIP + alanine

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Julie V Warnøe, MD; Phone Number: +4527282263; Email: julie.vilhelmine.warnoee.nielsen@regionh.dk

Study Locations

• Denmark
  • Capital Region
    • Hellerup, Capital Region, Denmark, 2900
      • Recruiting
      • Center for Clinical Metabolic Research, Gentofte Hospital
      • Contact: Filip K. Knop, MD, PhD; Phone Number: +4526830161; Email: filip.krag.knop.01@regionh.dk
      • Sub-Investigator: Julie V. Warnøe, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Saline; Intravenous administration of saline for 90 minutes.	Other: Placebo (saline); Intravenous saline during experimental days.
Experimental: GIP; Intravenous administration of GIP for 90 minutes (priming dose 6 pmol/kg/min for 10 minutes and 4 pmol/kg for 80 minutes.	Drug: GIP; Intravenous GIP administration during experimental days.
Experimental: Alanine; Intravenous administration of alanine for 90 minutes (28 umol/kg/min).	Drug: Alanine; Intravenous alanine administration during experimental days.
Experimental: GIP + Alanine; Intravenous 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.	Drug: GIP + alanine; Intravenous administration of GIP and alanine during experimental days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentrations of Glucagon	Baseline	Timepoint -30 to 90 minutes
Plasma concentrations of Glucagon	Baseline-corrected area under the curve (bsAUC)	Timepoint -30 to 90 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum concentration of Insulin	Baseline	Timepoint -30 to 90 minutes
Serum concentration of Insulin	Baseline-corrected area under the curve (bsAUC).	Timepoint -30 to 90 minutes
Serum concentration of C-peptid	Baseline	Timepoint -30 to 90 minutes
Serum concentration of C-peptid	Baseline-corrected area under the curve (bsAUC).	Timepoint -30 to 90 minutes
Plasma concentration of glucose	Baseline	Timepoint -30 to 90 minutes
Plasma concentration of glucose	Baseline-corrected area under the curve (bsAUC).	Timepoint -30 to 90 minutes
Plasma concentration of glucose	Peak value	Timepoint -30 to 90 minutes
Plasma concentration of GIP	Baseline	Timepoint -30 to 90 minutes
Plasma concentration of GIP	Baseline-corrected area under the curve (bsAUC).	Timepoint -30 to 90 minutes
Circulating levels of total amino acids	Baseline	Timepoint -30 to 90 minutes
Circulating levels of total amino acids	Baseline-corrected area under the curve (bsAUC).	Timepoint -30 to 90 minutes
Circulating levels of individual amino acids	Baseline	Timepoint -30 to 90 minutes
Circulating levels of individual amino acids	Baseline-corrected area under the curve (bsAUC).	Timepoint -30 to 90 minutes
Lipid profile	Baseline	Timepoint -30 to 90 minutes
Lipid profile	Baseline-corrected area under the curve (bsAUC).	Timepoint -30 to 90 minutes
Circulating levels of CTx	Baseline	Timepoint -30 to 90 minutes
Circulating levels of CTx	Baseline-corrected area under the curve (bsAUC).	Timepoint -30 to 90 minutes
Circulating levels of P1NP	Baseline	Timepoint -30 to 90 minutes
Circulating levels of P1NP	Baseline-corrected area under the curve (bsAUC).	Timepoint -30 to 90 minutes
Blood pressure	Baseline	Timepoint -30, 0, 30, 60, 90
Blood pressure	Baseline-corrected area under the curve (bsAUC).	Timepoint -30, 0, 30, 60, 90
Pulse	Baseline	Timepoint -30, 0, 30, 60, 90
Pulse	Baseline-corrected area under the curve (bsAUC).	Timepoint -30, 0, 30, 60, 90

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen
• Investigators: Principal Investigator: Filip K Knop, MD, PhD, Center for Clinical Metabolic Research, Gentofte Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: May 13, 2024
• First Submitted That Met QC Criteria: May 13, 2024
• First Posted (Actual): May 17, 2024

Study Record Updates

• Last Update Posted (Actual): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 13, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: H-21066812

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No