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

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

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

Study Overview

• Status: Completed
• Conditions: Glucose Metabolism Disorders
• Intervention / Treatment: Drug: Acarbose; Drug: Placebo Oral Tablet; Drug: Exendin (9-39); Drug: Placebo Saline

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Hellerup, Denmark, 2900
    • Center for Diabetesresearch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Acarbose; 50 mg and 100 mg glucobay tablets. 2 weeks. Other name: Precose	Drug: Acarbose; Glucobay tablets on experimental day.; Other Names: Glucobay, Precose
PLACEBO_COMPARATOR: Placebo Oral tablets; 180 mg. 2 weeks.	Drug: Placebo Oral Tablet; Placebo tablets on experimental day.
EXPERIMENTAL: Exendin (9-39); Infusion of GLP-1 receptor antagonist as a study tool to block GLP-1 activity on experimental day.	Drug: Exendin (9-39); Infusion of GLP-1 receptor antagonist as a study tool to block GLP-1 activity on experimental day.; Other Names: Ex(9-39)
PLACEBO_COMPARATOR: Placbo Saline; 9 mg/ml placebo saline infusion on experimental day.	Drug: Placebo Saline; 9 mg/ml placebo saline infusion on experimental day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen
• Collaborators: University of Copenhagen
• Investigators: Study Director: Filip K Knop, MD, PhD, University Hospital, Gentofte, Copenhagen

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2017
• Primary Completion (ACTUAL): January 1, 2018
• Study Completion (ACTUAL): January 1, 2018

Study Registration Dates

• First Submitted: August 2, 2017
• First Submitted That Met QC Criteria: August 4, 2017
• First Posted (ACTUAL): August 7, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 26, 2020
• Last Update Submitted That Met QC Criteria: March 25, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: alpha-glucosidase inhibitor; acarbose; Glp-1
• Additional Relevant MeSH Terms: Metabolic Diseases; Glucose Metabolism Disorders; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Acarbose
• Other Study ID Numbers: H-17007893

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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