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The Effect of Insulin-induced Hypoglycaemia on Gut-derived Glucagon Secretion (Px-Hypo)

Primary Purpose

Diabetes After Total Pancreatectomy

Status

Completed

Phase

Not Applicable

Locations

Denmark

Study Type

Interventional

Intervention

Oral glucose tolerance test

Clamp experiment

About this trial

This is an interventional basic science trial for Diabetes After Total Pancreatectomy focused on measuring glucagon

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Pancreatectomised patients

Caucasian above 30 years of age who have undergone total pancreatectomy
Blood haemoglobin >7.0 mmol/l for males and >6.5 mmol/l for females Non-diabetic control subjects
Normal fasting plasma glucose and normal HbA1c (according to the World Health Organization (WHO) criteria)
Normal blood haemoglobin
Caucasian above 30 years of age
BMI (body mass index) 17-30
Informed consent

Exclusion Criteria:

Pancreatectomised patients

Pancreatectomy within the last 3 months
Ongoing chemotherapy or chemotherapy within the last 3 months
Previous or ongoing treatment with GLP-1 receptor agonists or dipeptidyl peptidase 4 (DPP-4) inhibitors
Inflammatory bowel disease
Gastrointestinal resection (other than the gastro-duodenectomy performed in connection with total pancreatectomy) and/or ostomy
Nephropathy (eGFR<60 and/or albuminuria)
Known liver disease (excluding non-alcoholic fatty liver disease) and/or serum alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >3 × normal values)
Severe lung disease
Pregnancy and/or breastfeeding
Age above 85 years
Uncontrolled hypertension and/or significant cardiovascular disease
Any condition that the investigator feels would interfere with trial participation Non-diabetic control subjects
Diabetes or prediabetes (according to WHO criteria)
First-degree relatives with diabetes
Inflammatory bowel disease
Gastrointestinal resection and/or ostomy
Nephropathy (serum creatinine >150 µmol/l and/or albuminuria)
Known liver disease (excluding non-alcoholic fatty liver disease) and/or serum ALAT and/or serum ASAT >3 × normal values)
Severe lung disease
Pregnancy and/or breastfeeding
Age above 85 years
Uncontrolled hypertension and/or significant cardiovascular disease
Any condition that the investigator feels would interfere with trial participation

Sites / Locations

Center for Clinical Metabolic Research

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Totally pancreatectomized patients

Healthy controls

Arm Description

Oral glucose tolerance test + insulin-induced hypoglycaemic clamp followed by an oral glucose tolerance test

Outcomes

Primary Outcome Measures

p-glucagon

Plasma glucagon excursions measured as incremental area under the curve (iAUC)

Secondary Outcome Measures

p-glucose

plasma glucose excursions measured as incremental area under the curve (iAUC)

GIP, GLP-1, GLP-2, GIP, oxyntomodulin, ghrelin, peptide YY, gastrin

excursions in Gut hormones measured as incremental area under the curve (iAUC)

catecholamines

p-adrenaline and p-noradrenaline, excursions measured as incremental area under the curve (iAUC)

cortisol

p-cortisol excursions measured as incremental area under the curve (iAUC)

growth hormone

p-growth hormone excursions measured as incremental area under the curve (iAUC)

Full Information

NCT ID

NCT04064203

First Posted

August 16, 2019

Last Updated

August 19, 2019

Sponsor

University Hospital, Gentofte, Copenhagen

Collaborators

University of Copenhagen

1. Study Identification

Unique Protocol Identification Number

NCT04064203

Brief Title

The Effect of Insulin-induced Hypoglycaemia on Gut-derived Glucagon Secretion (Px-Hypo)

Official Title

The Effect of Insulin-induced Hypoglycaemia on Gut-derived Glucagon Secretion

Study Type

Interventional

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Completed

Study Start Date

July 5, 2017 (Actual)

Primary Completion Date

September 20, 2018 (Actual)

Study Completion Date

September 20, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University Hospital, Gentofte, Copenhagen

Collaborators

University of Copenhagen

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The overall objective of this study is to investigate whether hypoglycaemia (the most potent stimulus of pancreatic glucagon secretion) affects the secretion of gut-derived glucagon in totally pancreatectomized patients.

Detailed Description

The investigators want to assess the plasma glucagon response to insulin-induced hypoglycaemia in totally pancreatectomised patients and at the same time evaluate whether hypoglycaemia affects a range of other products from endocrine cells in the gastrointestinal tract including ghrelin, gastrin, cholecystokinin (CCK), glucose-dependent insulinotropic polypeptide (GIP), GLP-1, glucagon-like peptide-2 (GLP-2), oxyntomodulin and peptide YY (PYY). Furthermore the investigators will evaluate how hypoglycaemia in these patients affects other counter-regulatory mechanisms including plasma responses of the hormones adrenaline, noradrenaline, growth hormone and cortisol as well as the rate of gastric emptying rate (which under normal circumstances accelerates during hypoglycaemia) during an oral glucose tolerance test (OGTT).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes After Total Pancreatectomy

Keywords

glucagon

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

12 totally pancreatectomized patients and 12 healthy control subjects

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Totally pancreatectomized patients

Arm Type

Experimental

Arm Description

Oral glucose tolerance test + insulin-induced hypoglycaemic clamp followed by an oral glucose tolerance test

Arm Title

Healthy controls

Arm Type

Experimental

Arm Description

Oral glucose tolerance test + insulin-induced hypoglycaemic clamp followed by an oral glucose tolerance test

Intervention Type

Other

Intervention Name(s)

Oral glucose tolerance test

Intervention Description

50 grams OGTT

Intervention Type

Other

Intervention Name(s)

Clamp experiment

Intervention Description

insulin-induced hypoglycaemic clamp followed by an 50 grams OGTT

Primary Outcome Measure Information:

Title

p-glucagon

Description

Plasma glucagon excursions measured as incremental area under the curve (iAUC)

Time Frame

-30, -15, 0, 15, 40, 50, 60, 70, 80, 90, 105, 120, 135, 150, 165, 180, 210, 240 minutes

Secondary Outcome Measure Information:

Title

p-glucose

Description

plasma glucose excursions measured as incremental area under the curve (iAUC)

Time Frame

-30, -15, 0, 15, 40, 50, 60, 70, 80, 90, 105, 120, 135, 150, 165, 180, 210, 240 minutes

Title

GIP, GLP-1, GLP-2, GIP, oxyntomodulin, ghrelin, peptide YY, gastrin

Description

excursions in Gut hormones measured as incremental area under the curve (iAUC)

Time Frame

-30, -15, 0, 15, 40, 50, 60, 70, 80, 90, 105, 120, 135, 150, 165, 180, 210, 240 minutes

Title

catecholamines

Description

p-adrenaline and p-noradrenaline, excursions measured as incremental area under the curve (iAUC)

Time Frame

-30, -15, 0, 15, 40, 50, 60, 70, 80, 90 minutes

Title

cortisol

Description

p-cortisol excursions measured as incremental area under the curve (iAUC)

Time Frame

-30, -15, 0, 15, 40, 50, 60, 70, 80, 90 minutes

Title

growth hormone

Description

p-growth hormone excursions measured as incremental area under the curve (iAUC)

Time Frame

-30, -15, 0, 15, 40, 50, 60, 70, 80, 90 minutes

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Pancreatectomised patients Caucasian above 30 years of age who have undergone total pancreatectomy Blood haemoglobin >7.0 mmol/l for males and >6.5 mmol/l for females Non-diabetic control subjects Normal fasting plasma glucose and normal HbA1c (according to the World Health Organization (WHO) criteria) Normal blood haemoglobin Caucasian above 30 years of age BMI (body mass index) 17-30 Informed consent Exclusion Criteria: Pancreatectomised patients Pancreatectomy within the last 3 months Ongoing chemotherapy or chemotherapy within the last 3 months Previous or ongoing treatment with GLP-1 receptor agonists or dipeptidyl peptidase 4 (DPP-4) inhibitors Inflammatory bowel disease Gastrointestinal resection (other than the gastro-duodenectomy performed in connection with total pancreatectomy) and/or ostomy Nephropathy (eGFR<60 and/or albuminuria) Known liver disease (excluding non-alcoholic fatty liver disease) and/or serum alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >3 × normal values) Severe lung disease Pregnancy and/or breastfeeding Age above 85 years Uncontrolled hypertension and/or significant cardiovascular disease Any condition that the investigator feels would interfere with trial participation Non-diabetic control subjects Diabetes or prediabetes (according to WHO criteria) First-degree relatives with diabetes Inflammatory bowel disease Gastrointestinal resection and/or ostomy Nephropathy (serum creatinine >150 µmol/l and/or albuminuria) Known liver disease (excluding non-alcoholic fatty liver disease) and/or serum ALAT and/or serum ASAT >3 × normal values) Severe lung disease Pregnancy and/or breastfeeding Age above 85 years Uncontrolled hypertension and/or significant cardiovascular disease Any condition that the investigator feels would interfere with trial participation

Facility Information:

Facility Name

Center for Clinical Metabolic Research

City

Hellerup

State/Province

Capital Region

ZIP/Postal Code

2900

Country

Denmark

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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The Effect of Insulin-induced Hypoglycaemia on Gut-derived Glucagon Secretion (Px-Hypo)

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