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

Sponsor

Steno Diabetes Center Copenhagen (Other)

Overall Status

Completed

CT.gov ID

NCT03556098

Collaborator

(none)

Enrollment

Location

Arms

11.6

Actual Duration (Months)

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: glucose-dependent insulinotropic peptide Drug: Glucose-Dependent Insulin-Releasing Hormone[3-30] Drug: Saline Solution	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Double blinded, randomized, cross-over studyDouble blinded, randomized, cross-over study

Masking:

Double (Participant, Investigator)

Masking Description:

The peptides/placebo is prepared, in a randomized fashion, by a laboratory assistant..

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Feb 22, 2019

Actual Primary Completion Date :

Feb 11, 2020

Actual Study Completion Date :

Feb 11, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: GIP Infusion of Glucose-dependent insulinotropic peptide	Drug: glucose-dependent insulinotropic peptide Infusion of GIP
Active Comparator: GIP[3-30] Infusion of GIP[3-30]	Drug: Glucose-Dependent Insulin-Releasing Hormone[3-30] Infusion of GIP antagonist GIP[3-30]
Placebo Comparator: Saline Infusion of saline	Drug: Saline Solution Infusion of Saline Other Names: Placebo

Arm

Intervention/Treatment

Active Comparator: GIP

Infusion of Glucose-dependent insulinotropic peptide

Drug: glucose-dependent insulinotropic peptide

Infusion of GIP

Active Comparator: GIP[3-30]

Infusion of GIP[3-30]

Drug: Glucose-Dependent Insulin-Releasing Hormone[3-30]

Infusion of GIP antagonist GIP[3-30]

Placebo Comparator: Saline

Infusion of saline

Drug: Saline Solution

Infusion of Saline

Other Names:

Placebo

Outcome Measures

Primary Outcome Measures

plasma glucose concentration [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]
plasma glucose excursions and plasma glucose nadir

Secondary Outcome Measures

Glucose regulatory hormones [At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days]
Counter regulatory hormones: glucagon, noradrenalin, cortisol, somatotropin, and insulin/c-peptide. Incremental and total area under the Concentration-Time Curve
Incretin hormones [At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days]
Incretin hormones GLP-1 and GIP. Incremental and total area under the Concentration-Time Curve
GIP[3-30] [At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days]
GIP[3-30]. Incremental and total area under the Concentration-Time Curve
Free fatty acids (FFA) [At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days]
Free fatty acids(FFA). Incremental and total area under the Concentration-Time Curve
Blood analysis of paracetamol as an assessment of gastric emptying [At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days]
Assessment of gastric emptying
Fat mRNA [At time 240 minute on study days]
Fat biopsy to evaluate changes in fat mRNA
Fat Lipoprotein lipase (LPL) [At time 240 minute on study days]
Fat biopsy to evaluate LPL changes in fat
Fat Perilipin 4 [At time 240 minute on study days]
Fat biopsy to evaluate Perilipin 4 changes in fat
Fat Fatty acid binding protein 4 (FABP4) [At time 240 minute on study days]
Fat biopsy to evaluate Fatty acid binding protein 4 (FABP4) changes in fat
Fat Hormonse-sensitive lipase (HSL) [At time 240 minute on study days]
Fat biopsy to evaluate Hormonse-sensitive lipase (HSL) changes in fat
Fat Vascular endothelial growth factor 4 (VEGF-A) [At time 240 minute on study days]
Fat biopsy to evaluate Vascular endothelial growth factor 4 (VEGF-A) changes in fat
Fat GIP receptor (GIPR) [At time 240 minute on study days]
Fat biopsy to evaluate GIP receptor (GIPR) changes in fat
Blood pressure [At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days]
Changes in blood pressure, mm Hg
Pulse [At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days]
Changes in pulse, beats per minute

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Male

Accepts 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