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Glucose-dependent Insulinotropic Polypeptide as a Safeguard Against Hypoglycemia in Patients With Type 1 Diabetes

Primary Purpose

Diabetes Mellitus, Type 1

Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
glucose-dependent insulinotropic peptide
Glucose-Dependent Insulin-Releasing Hormone[3-30]
Saline Solution
Sponsored by
Steno Diabetes Center Copenhagen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Diabetes Mellitus, Type 1 focused on measuring Diabetes Mellitus, Type 1, Hypoglycemia, Gastric Inhibitory Polypeptide, Glucagon, Incretin

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Caucasian men
  • Body mass index between 20-27 kg/m^2
  • T1D (diagnosed according to the criteria of the World Health Organization) with HbA1c<69 mmol/l (<8,5%)
  • T1D duration between 2-20 years
  • Stimulated C-peptide ≤ 100 pmol/mL)
  • Treatment with a stable basal bolus or insulin pump regimen ≥ 3 months
  • Informed consent

Exclusion Criteria:

  • Anemia (hemoglobin below normal range)
  • Liver disease (ALAT and/or ASAT >2 times normal values) or history of hepatobiliary disorder
  • Nephropathy (serum creatinine above normal range and/or albuminuria)
  • 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 fells would interfere with trial participation
  • Treatment with any glucose-lowering drugs beside insulin

Sites / Locations

  • Steno Diabetes Center Copenhagen, Clinical Metabolic Physiology

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

GIP

GIP[3-30]

Saline

Arm Description

Infusion of Glucose-dependent insulinotropic peptide

Infusion of GIP[3-30]

Infusion of saline

Outcomes

Primary Outcome Measures

plasma glucose concentration
plasma glucose excursions and plasma glucose nadir

Secondary Outcome Measures

Glucose regulatory hormones
Counter regulatory hormones: glucagon, noradrenalin, cortisol, somatotropin, and insulin/c-peptide. Incremental and total area under the Concentration-Time Curve
Incretin hormones
Incretin hormones GLP-1 and GIP. Incremental and total area under the Concentration-Time Curve
GIP[3-30]
GIP[3-30]. Incremental and total area under the Concentration-Time Curve
Free fatty acids (FFA)
Free fatty acids(FFA). Incremental and total area under the Concentration-Time Curve
Blood analysis of paracetamol as an assessment of gastric emptying
Assessment of gastric emptying
Fat mRNA
Fat biopsy to evaluate changes in fat mRNA
Fat Lipoprotein lipase (LPL)
Fat biopsy to evaluate LPL changes in fat
Fat Perilipin 4
Fat biopsy to evaluate Perilipin 4 changes in fat
Fat Fatty acid binding protein 4 (FABP4)
Fat biopsy to evaluate Fatty acid binding protein 4 (FABP4) changes in fat
Fat Hormonse-sensitive lipase (HSL)
Fat biopsy to evaluate Hormonse-sensitive lipase (HSL) changes in fat
Fat Vascular endothelial growth factor 4 (VEGF-A)
Fat biopsy to evaluate Vascular endothelial growth factor 4 (VEGF-A) changes in fat
Fat GIP receptor (GIPR)
Fat biopsy to evaluate GIP receptor (GIPR) changes in fat
Blood pressure
Changes in blood pressure, mm Hg
Pulse
Changes in pulse, beats per minute

Full Information

First Posted
April 16, 2018
Last Updated
May 5, 2021
Sponsor
Steno Diabetes Center Copenhagen
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1. Study Identification

Unique Protocol Identification Number
NCT03556098
Brief Title
Glucose-dependent Insulinotropic Polypeptide as a Safeguard Against Hypoglycemia in Patients With Type 1 Diabetes
Official Title
Glucose-dependent Insulinotropic Polypeptide as a Safeguard Against Hypoglycemia in Patients With Type 1 Diabetes
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
February 22, 2019 (Actual)
Primary Completion Date
February 11, 2020 (Actual)
Study Completion Date
February 11, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Steno Diabetes Center Copenhagen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In the present project the investigators will evaluate whether glucagonotropic properties of the gut-derived incretin hormone glucose-dependent insulinotropic polypeptide (GIP) may be utilized as a safeguard against hypoglycemia in patients with T1D.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1
Keywords
Diabetes Mellitus, Type 1, Hypoglycemia, Gastric Inhibitory Polypeptide, Glucagon, Incretin

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
Double blinded, randomized, cross-over study
Masking
ParticipantInvestigator
Masking Description
The peptides/placebo is prepared, in a randomized fashion, by a laboratory assistant..
Allocation
Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GIP
Arm Type
Active Comparator
Arm Description
Infusion of Glucose-dependent insulinotropic peptide
Arm Title
GIP[3-30]
Arm Type
Active Comparator
Arm Description
Infusion of GIP[3-30]
Arm Title
Saline
Arm Type
Placebo Comparator
Arm Description
Infusion of saline
Intervention Type
Drug
Intervention Name(s)
glucose-dependent insulinotropic peptide
Intervention Description
Infusion of GIP
Intervention Type
Drug
Intervention Name(s)
Glucose-Dependent Insulin-Releasing Hormone[3-30]
Intervention Description
Infusion of GIP antagonist GIP[3-30]
Intervention Type
Drug
Intervention Name(s)
Saline Solution
Other Intervention Name(s)
Placebo
Intervention Description
Infusion of Saline
Primary Outcome Measure Information:
Title
plasma glucose concentration
Description
plasma glucose excursions and plasma glucose nadir
Time Frame
At times (minute): - 30, - 15, 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210, 225, 240 on study days
Secondary Outcome Measure Information:
Title
Glucose regulatory hormones
Description
Counter regulatory hormones: glucagon, noradrenalin, cortisol, somatotropin, and insulin/c-peptide. Incremental and total area under the Concentration-Time Curve
Time Frame
At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days
Title
Incretin hormones
Description
Incretin hormones GLP-1 and GIP. Incremental and total area under the Concentration-Time Curve
Time Frame
At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days
Title
GIP[3-30]
Description
GIP[3-30]. Incremental and total area under the Concentration-Time Curve
Time Frame
At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days
Title
Free fatty acids (FFA)
Description
Free fatty acids(FFA). Incremental and total area under the Concentration-Time Curve
Time Frame
At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days
Title
Blood analysis of paracetamol as an assessment of gastric emptying
Description
Assessment of gastric emptying
Time Frame
At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days
Title
Fat mRNA
Description
Fat biopsy to evaluate changes in fat mRNA
Time Frame
At time 240 minute on study days
Title
Fat Lipoprotein lipase (LPL)
Description
Fat biopsy to evaluate LPL changes in fat
Time Frame
At time 240 minute on study days
Title
Fat Perilipin 4
Description
Fat biopsy to evaluate Perilipin 4 changes in fat
Time Frame
At time 240 minute on study days
Title
Fat Fatty acid binding protein 4 (FABP4)
Description
Fat biopsy to evaluate Fatty acid binding protein 4 (FABP4) changes in fat
Time Frame
At time 240 minute on study days
Title
Fat Hormonse-sensitive lipase (HSL)
Description
Fat biopsy to evaluate Hormonse-sensitive lipase (HSL) changes in fat
Time Frame
At time 240 minute on study days
Title
Fat Vascular endothelial growth factor 4 (VEGF-A)
Description
Fat biopsy to evaluate Vascular endothelial growth factor 4 (VEGF-A) changes in fat
Time Frame
At time 240 minute on study days
Title
Fat GIP receptor (GIPR)
Description
Fat biopsy to evaluate GIP receptor (GIPR) changes in fat
Time Frame
At time 240 minute on study days
Title
Blood pressure
Description
Changes in blood pressure, mm Hg
Time Frame
At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days
Title
Pulse
Description
Changes in pulse, beats per minute
Time Frame
At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Caucasian men Body mass index between 20-27 kg/m^2 T1D (diagnosed according to the criteria of the World Health Organization) with HbA1c<69 mmol/l (<8,5%) T1D duration between 2-20 years Stimulated C-peptide ≤ 100 pmol/mL) Treatment with a stable basal bolus or insulin pump regimen ≥ 3 months Informed consent Exclusion Criteria: Anemia (hemoglobin below normal range) Liver disease (ALAT and/or ASAT >2 times normal values) or history of hepatobiliary disorder Nephropathy (serum creatinine above normal range and/or albuminuria) 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 fells would interfere with trial participation Treatment with any glucose-lowering drugs beside insulin
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Filip K Knop, MD, PhD
Organizational Affiliation
Steno Diabetes Center Copenhagen, Clinical Metabolic Physiology
Official's Role
Study Director
Facility Information:
Facility Name
Steno Diabetes Center Copenhagen, Clinical Metabolic Physiology
City
Hellerup
ZIP/Postal Code
2900
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Glucose-dependent Insulinotropic Polypeptide as a Safeguard Against Hypoglycemia in Patients With Type 1 Diabetes

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