MedDataX Logo

Dissection of the Gastrointestinal-mediated Glucose Disposal and Incretin Defect in Patients With Type 2 Diabetes

NCT ID: NCT02669524

Last Updated: 2016-10-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-10-31

Study Completion Date

2016-08-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

In patients with type 2 diabetes, the incretin effect is markedly reduced contributing to the relative insulin deficiency that characterizes these patients. This defect is believed to be due to a decreased effect of GLP-1 and an almost ceased effect of GIP. Nevertheless, the impact of the defect on glucose tolerance is not fully understood. The so-called gastrointestinal-mediated glucose disposal (GIGD) is a measure of glucose handling, which includes the incretin effect, but also other factors affecting glucose disposal (e.g. glucagon secretion). Interestingly, patients with type 2 diabetes exhibit elevated plasma glucagon levels in the fasting state, and glucagon concentrations fail to decrease appropriately and may even increase in response to ingestion of glucose and show exaggerated increases after a mixed meal. With the current project the investigators wish to elucidate how this paradoxical glucagon response observed in patients with type 2 diabetes affects the GIGD, the incretin effect and postprandial glucose excursions.

Ten patients with type 2 diabetes and 10 healthy matched control subjects will be enrolled in this randomised, placebo-controlled, double-blinded study. The aim is to examine the effect of a glucagon receptor antagonist (GRA) on gastrointestinal-mediated glucose disposal (GIGD), incretin effect and postprandial glucose excursions in patients with type 2 diabetes and healthy controls. Participants will attend two oral glucose tolerance tests (OGTT), two isoglycaemic iv glucose infusion (IIGI) and two standardised liquid meals.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Type 2 Diabetes

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

T2D + OGTT + LY2409021

Type 2 diabetes patients + 50 oral glucose tolerance test 4 hours + the human antagonist of the glucagon receptor.

Group Type ACTIVE_COMPARATOR

LY2409021

Intervention Type DRUG

OGTT

Intervention Type PROCEDURE

T2D + OGTT + placebo

Type 2 diabetes patients + 50 oral glucose tolerance test 4 hours + placebo comparator to the human antagonist of the glucagon receptor.

Group Type PLACEBO_COMPARATOR

LY2409021 placebo

Intervention Type DRUG

OGTT

Intervention Type PROCEDURE

T2D + IIGI + LY2409021

Type 2 diabetes patients + isoglycaemic iv glucose infusion + the human antagonist of the glucagon receptor.

Group Type ACTIVE_COMPARATOR

LY2409021

Intervention Type DRUG

IIGI

Intervention Type PROCEDURE

T2D + IIGI + placebo

Type 2 diabetes patients + isoglycaemic iv glucose infusion + placebo comparator to the human antagonist of the glucagon receptor.

Group Type PLACEBO_COMPARATOR

LY2409021 placebo

Intervention Type DRUG

IIGI

Intervention Type PROCEDURE

T2D + MEAL + LY2409021

Type 2 diabetes patients + Standardised liquid meal + the human antagonist of the glucagon receptor.

Group Type ACTIVE_COMPARATOR

LY2409021

Intervention Type DRUG

Standardised liquid meal

Intervention Type PROCEDURE

T2D + MEAL + placebo

Type 2 diabetes patients + Standardised liquid meal + placebo comparator to the human antagonist of the glucagon receptor.

Group Type PLACEBO_COMPARATOR

LY2409021 placebo

Intervention Type DRUG

Standardised liquid meal

Intervention Type PROCEDURE

CTRL + OGTT + LY2409021

Healthy controls + 50 oral glucose tolerance test 4 hours + the human antagonist of the glucagon receptor.

Group Type ACTIVE_COMPARATOR

LY2409021

Intervention Type DRUG

OGTT

Intervention Type PROCEDURE

CTRL + OGTT + placebo

Healthy controls + 50 oral glucose tolerance test 4 hours + placebo comparator of the human antagonist of the glucagon receptor.

Group Type PLACEBO_COMPARATOR

LY2409021 placebo

Intervention Type DRUG

OGTT

Intervention Type PROCEDURE

CTRL + IIGI + LY2409021

Healthy controls + isoglycaemic iv glucose infusion + the human antagonist of the glucagon receptor.

Group Type ACTIVE_COMPARATOR

LY2409021

Intervention Type DRUG

IIGI

Intervention Type PROCEDURE

CTRL + IIGI + placebo

Healthy controls + isoglycaemic iv glucose infusion + placebo comparator the human antagonist of the glucagon receptor.

Group Type PLACEBO_COMPARATOR

LY2409021 placebo

Intervention Type DRUG

IIGI

Intervention Type PROCEDURE

CTRL + MEAL + LY2409021

Healthy controls + Standardised liquid meal + the human antagonist of the glucagon receptor.

Group Type ACTIVE_COMPARATOR

LY2409021

Intervention Type DRUG

Standardised liquid meal

Intervention Type PROCEDURE

CTRL + MEAL + placebo

Healthy controls + Standardised liquid meal + placebo comparator of the human antagonist of the glucagon receptor.

Group Type PLACEBO_COMPARATOR

LY2409021 placebo

Intervention Type DRUG

Standardised liquid meal

Intervention Type PROCEDURE

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

LY2409021

Intervention Type DRUG

LY2409021 placebo

Intervention Type DRUG

OGTT

Intervention Type PROCEDURE

IIGI

Intervention Type PROCEDURE

Standardised liquid meal

Intervention Type PROCEDURE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

Patients with type 2 diabetes

* Caucasians above 35 years of age with diet or metformin treated type 2 diabetes for at least 3 month (diagnosed according to the criteria of the World Health Organization (WHO)
* Normal haemoglobin
* Informed consent

Healthy subjects

* Normal fasting plasma glucose (FPG) \<6.1 mmol/l and HbA1c \<42 mmol/mol (6.0%)
* Normal haemoglobin
* Age above 35 years
* Informed consent

Exclusion Criteria

Patients with type 2 diabetes

* Inflammatory bowel disease
* Intestinal resections
* Nephropathy (serum creatinine above normal range and/or albuminuria)
* Liver disease (serum alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) \>2×normal values)
* Treatment with medicine that cannot be paused for 12 hours
* Pregnancy and/or breastfeeding
* Family history of pancreatic islet tumours
* Age above 80 years

Healthy subjects

* Diabetes or prediabetes with reduced glucose tolerance: FPG \>6.0 mmol/l and/or HbA1c \>42 mmol/mol
* First degree relatives with type 2 diabetes
* Inflammatory bowel disease
* Intestinal resections
* Treatment with medicine that cannot be paused for 12 hours
* Pregnancy and/or breastfeeding
* Age above 80 years
Minimum Eligible Age

35 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Eli Lilly and Company

INDUSTRY

Sponsor Role collaborator

University Hospital, Gentofte, Copenhagen

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Sofie Hædersdal

MD, PhD student

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Center for Diabetes Research, Gentofte Hospital, Copenhagen University

Hellerup, , Denmark

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Denmark

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

H-15007312

Identifier Type: -

Identifier Source: org_study_id