Delineation of the Role of Glucagon-like Peptide-1 Signalling in Relation to Increased Carbohydrate Content in the Distal Small Intestines

Glucose Metabolism Disorders Clinical Trial

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Official title:

The Role of Glucagon-like Peptide-1 Receptor Signalling in the Glucose-lowering Effect of Increased Carbohydrate Content in the Distal Small Intestines After Meal Ingestion in Patients With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03241303
• Other study ID #: H-17007893
• Status: Completed
• Phase: N/A
• Start date: August 1, 2017
• Est. completion date: January 1, 2018

Study information

• Verified date: March 2020
• Source: University Hospital, Gentofte, Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Investigation of GLP-1 signalling in the glucose-lowering effect of increased carbohydrate content in the distal small intestines induced by alpha-glucosidase inhibition during meal ingestion in patients with type 2 diabetes

Description:

The primary aim of the study is to investigate whether GLP-1 released as a result of increased carbohydrate content in the distal and L cell-rich part of the small intestine after a meal affects postprandial plasma glucose levels in patients with type 2 diabetes. This will be done by applying an alpha-glucosidase inhibitor (to increase the postprandial carbohydrate content in the distal small intestine) and the specific GLP-1 receptor antagonist exendin(9-39) (to isolate any GLP-1-mediated effects) during meal tests in patients with type 2 diabetes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: January 1, 2018
• Est. primary completion date: January 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Type 2 diabetes for at least three months (diagnosed according to the criteria of the World Health Organization (WHO)) treated with metformin monotherapy

• Caucasian ethnicity

• Normal haemoglobin

• Age >18 years

• BMI >23 kg/m2 and <35 kg/m2

• Informed and written consent

Exclusion Criteria:

• Liver disease (alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >2 times normal values) or history of hepatobiliary disorder

• Gastrointestinal disease, previous intestinal resection, cholecystectomy or any major intra-abdominal surgery

• Reduced kidney function or nephropathy (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 (based on serum creatinine) and/or albuminuria

• Treatment with medicine that cannot be paused for 12 hours

• Intake of antibiotics two months prior to study

• Treatment with glucose-lowering drugs other than metformin

• Hypo- and hyperthyroidism

• Treatment with oral anticoagulants

• Active or recent malignant disease

• Any treatment or condition requiring acute or sub-acute medical or surgical intervention

• Lack of effective birth control in premenopausal women

• Positive pregnancy test on study days in premenopausal women

• Pregnancy

• Women who are breastfeeding

• Any condition considered incompatible with participation by the investigators

• If the subjects receive any antibiotic treatment while included in the study they will be excluded

Related Conditions & MeSH terms

• Glucose Metabolism Disorders
• Metabolic Diseases

Intervention

Drug:
• Acarbose
Glucobay tablets on experimental day.
• Placebo Oral Tablet
Placebo tablets on experimental day.
• Exendin (9-39)
Infusion of GLP-1 receptor antagonist as a study tool to block GLP-1 activity on experimental day.
• Placebo Saline
9 mg/ml placebo saline infusion on experimental day.

Locations

Country	Name	City	State
Denmark	Center for Diabetesresearch	Hellerup

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Gentofte, Copenhagen	University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma glucose	The primary outcome is the difference between the effect of increased carbohydrate content in the distal part of the small intestine (obtained by inhibiting alpha-glucosidase with acarbose) on postprandial glucose tolerance (as assessed by area under curve (AUC) for plasma glucose during a standardised liquid mixed meal test) with and without blockade of GLP-1 signalling by exendin(9-39).	240 min