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

Sponsor

University Hospital, Gentofte, Copenhagen (Other)

Overall Status

Completed

CT.gov ID

NCT03241303

Collaborator

University of Copenhagen (Other)

Enrollment

Location

Arms

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
Glucose Metabolism Disorders	Drug: Acarbose Drug: Placebo Oral Tablet Drug: Exendin (9-39) Drug: Placebo Saline	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

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

Actual Study Start Date :

Aug 1, 2017

Actual Primary Completion Date :

Jan 1, 2018

Actual Study Completion Date :

Jan 1, 2018

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

Plasma glucose [240 min]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Center for Diabetesresearch	Hellerup		Denmark	2900

Sponsors and Collaborators

University Hospital, Gentofte, Copenhagen
University of Copenhagen

Investigators

Study Director: Filip K Knop, MD, PhD, University Hospital, Gentofte, Copenhagen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Niels Bjørn Dalsgaard, Bachelor of Science, University Hospital, Gentofte, Copenhagen

ClinicalTrials.gov Identifier:

NCT03241303

Other Study ID Numbers:

H-17007893

First Posted:

Aug 7, 2017

Last Update Posted:

Mar 26, 2020

Last Verified:

Mar 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Niels Bjørn Dalsgaard, Bachelor of Science, University Hospital, Gentofte, Copenhagen

Glp-1

alpha-glucosidase inhibitor

acarbose

Additional relevant MeSH terms:

Metabolic Diseases

Glucose Metabolism Disorders

Acarbose

Study Results

No Results Posted as of Mar 26, 2020