The Role of Glucose-Dependent Insulinotropic Polypeptide in the Pathological Glucose Homeostasis Of Type 1 Diabetes
Primary Purpose
Diabetes Mellitus, Type 1, Hypoglycemia
Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
GIP
Sponsored by
About this trial
This is an interventional basic science trial for Diabetes Mellitus, Type 1 focused on measuring Gastric Inhibitory Polypeptide, Diabetes Mellitus, Type 1, Hypoglycemia, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Glucagon, Incretin
Eligibility Criteria
Inclusion Criteria:
- Body mass index between 20 and 27 kg/m2
- T1D (diagnosed according to the criteria of the World Health Organization) with HbA1c <69 mmol/mol (<8.5%)
- Treatment with a stable insulin regimen ≥3 months
- T1D duration between 2 and 15years
- C-peptide negative (C-peptide ≤ 16 ng/ml)
- Informed consent
Exclusion Criteria:
- Anemia (hemoglobin outside normal range)
- Known liver disease and/or ALAT and/or ASAT > 2 times normal values
- Estimated glomerular filtration rate (eGFR) ≤60 ml/min/1.73 m2 or albuminuria
- Prior Cardiovascular events and/or abnormal heart rate/blood pressure
- Use of anti-diabetic medicine (other than insulin), corticosteroids or other drugs affecting glucose metabolism during the study period or within 30 days prior to randomization
- Any physical or psychological condition that the investigator feels would interfere with trial participation
Sites / Locations
- Steno Diabetes Center CopenhagenSteno Diabetes Center Copenhagen, Clinical Metabolic Physiology
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Glucose-Dependent Insulinotropic Polypeptide
Placebo
Arm Description
6-day continuous infusion of Glucose-Dependent Insulinotropic Polypeptide
Saline
Outcomes
Primary Outcome Measures
Blood glucose
Time spent in hypoglycemia, near-normoglycemia and hyperglycemia
Secondary Outcome Measures
Incretin hormones
Incretin hormones GLP-1 and GIP. Incremental and total area under the Concentration-Time Curve
Free fatty acids (FFA)
Incremental and total area under the Concentration-Time Curve
Fat mRNA
mRNA analysis of fat biopsies
Fat Protein content
Protein analysis of fat biopsies
Blood pressure
Changes in blood pressure, mm Hg
Pulse
Changes in pulse, beats per minute
Glucose regulatory hormones
Counter regulatory hormones: glucagon, noradrenalin, cortisol, somatotropin, and insulin/c-peptide. Incremental and total area under the Concentration-Time Curve
Number of symptomatic hypoglycemic events
Self-reported events
Full Information
NCT ID
NCT03734718
First Posted
October 22, 2018
Last Updated
January 23, 2020
Sponsor
Steno Diabetes Center Copenhagen
1. Study Identification
Unique Protocol Identification Number
NCT03734718
Brief Title
The Role of Glucose-Dependent Insulinotropic Polypeptide in the Pathological Glucose Homeostasis Of Type 1 Diabetes
Official Title
The Role of Glucose-dependent Insulinotropic Polypeptide in the Pathological Glucose Homeostasis of Type 1 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
June 1, 2019 (Actual)
Primary Completion Date
December 12, 2019 (Actual)
Study Completion Date
December 31, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
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
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
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 the daily life of participants with type 1 Diabetes
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1, Hypoglycemia
Keywords
Gastric Inhibitory Polypeptide, Diabetes Mellitus, Type 1, Hypoglycemia, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Glucagon, Incretin
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
placebo-controlled, double-blinded, cross-over study
Masking
ParticipantCare ProviderInvestigator
Masking Description
The peptides/placebo is prepared, in a randomized fashion, by a laboratory assistant.
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Glucose-Dependent Insulinotropic Polypeptide
Arm Type
Active Comparator
Arm Description
6-day continuous infusion of Glucose-Dependent Insulinotropic Polypeptide
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Saline
Intervention Type
Drug
Intervention Name(s)
GIP
Intervention Description
Infusion of Glucose-dependent insulinotropic peptide
Primary Outcome Measure Information:
Title
Blood glucose
Description
Time spent in hypoglycemia, near-normoglycemia and hyperglycemia
Time Frame
an average of 6 days
Secondary Outcome Measure Information:
Title
Incretin hormones
Description
Incretin hormones GLP-1 and GIP. Incremental and total area under the Concentration-Time Curve
Time Frame
Evaluated at experimental day 0,1 and 6 of each intervention
Title
Free fatty acids (FFA)
Description
Incremental and total area under the Concentration-Time Curve
Time Frame
Evaluated at experimental day 0,1 and 6 of each intervention
Title
Fat mRNA
Description
mRNA analysis of fat biopsies
Time Frame
At day 6, and 10 of the study
Title
Fat Protein content
Description
Protein analysis of fat biopsies
Time Frame
Evaluated at experimental day 0,1 and 6 of each intervention
Title
Blood pressure
Description
Changes in blood pressure, mm Hg
Time Frame
The first 24 hours of intervention and at experimental day 6
Title
Pulse
Description
Changes in pulse, beats per minute
Time Frame
The first 24 hours of intervention and at experimental day 6
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
Evaluated at experimental day 0,1 and 6 of each intervention
Title
Number of symptomatic hypoglycemic events
Description
Self-reported events
Time Frame
An average of 1 week
10. Eligibility
Sex
Male
Gender Based
Yes
Gender Eligibility Description
Caucasian men
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Body mass index between 20 and 27 kg/m2
T1D (diagnosed according to the criteria of the World Health Organization) with HbA1c <69 mmol/mol (<8.5%)
Treatment with a stable insulin regimen ≥3 months
T1D duration between 2 and 15years
C-peptide negative (C-peptide ≤ 16 ng/ml)
Informed consent
Exclusion Criteria:
Anemia (hemoglobin outside normal range)
Known liver disease and/or ALAT and/or ASAT > 2 times normal values
Estimated glomerular filtration rate (eGFR) ≤60 ml/min/1.73 m2 or albuminuria
Prior Cardiovascular events and/or abnormal heart rate/blood pressure
Use of anti-diabetic medicine (other than insulin), corticosteroids or other drugs affecting glucose metabolism during the study period or within 30 days prior to randomization
Any physical or psychological condition that the investigator feels would interfere with trial participation
Facility Information:
Facility Name
Steno Diabetes Center CopenhagenSteno Diabetes Center Copenhagen, Clinical Metabolic Physiology
City
Hellerup
ZIP/Postal Code
2800
Country
Denmark
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
34405256
Citation
Heimburger SMN, Hoe B, Nielsen CN, Bergmann NC, Hartmann B, Holst JJ, Vilsboll T, Dejgaard TF, Christensen MB, Knop FK. The effect of 6-day subcutaneous glucose-dependent insulinotropic polypeptide infusion on time in glycaemic range in patients with type 1 diabetes: a randomised, double-blind, placebo-controlled crossover trial. Diabetologia. 2021 Nov;64(11):2425-2431. doi: 10.1007/s00125-021-05547-8. Epub 2021 Aug 17.
Results Reference
derived
Learn more about this trial
The Role of Glucose-Dependent Insulinotropic Polypeptide in the Pathological Glucose Homeostasis Of Type 1 Diabetes
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