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

Primary Purpose

Glucose Metabolism Disorders

Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Acarbose
Placebo Oral Tablet
Exendin (9-39)
Placebo Saline
Sponsored by
University Hospital, Gentofte, Copenhagen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Glucose Metabolism Disorders focused on measuring Glp-1, alpha-glucosidase inhibitor, acarbose

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Center for Diabetesresearch

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Acarbose

Placebo Oral tablets

Exendin (9-39)

Placbo Saline

Arm Description

50 mg and 100 mg glucobay tablets. 2 weeks. Other name: Precose

180 mg. 2 weeks.

Infusion of GLP-1 receptor antagonist as a study tool to block GLP-1 activity on experimental day.

9 mg/ml placebo saline infusion on experimental day.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Full Information

First Posted
August 2, 2017
Last Updated
March 25, 2020
Sponsor
University Hospital, Gentofte, Copenhagen
Collaborators
University of Copenhagen
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1. Study Identification

Unique Protocol Identification Number
NCT03241303
Brief Title
Delineation of the Role of Glucagon-like Peptide-1 Signalling in Relation to Increased Carbohydrate Content in the Distal Small Intestines
Acronym
AlfaEx
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
August 1, 2017 (Actual)
Primary Completion Date
January 1, 2018 (Actual)
Study Completion Date
January 1, 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
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glucose Metabolism Disorders
Keywords
Glp-1, alpha-glucosidase inhibitor, acarbose

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Acarbose
Arm Type
Experimental
Arm Description
50 mg and 100 mg glucobay tablets. 2 weeks. Other name: Precose
Arm Title
Placebo Oral tablets
Arm Type
Placebo Comparator
Arm Description
180 mg. 2 weeks.
Arm Title
Exendin (9-39)
Arm Type
Experimental
Arm Description
Infusion of GLP-1 receptor antagonist as a study tool to block GLP-1 activity on experimental day.
Arm Title
Placbo Saline
Arm Type
Placebo Comparator
Arm Description
9 mg/ml placebo saline infusion on experimental day.
Intervention Type
Drug
Intervention Name(s)
Acarbose
Other Intervention Name(s)
Glucobay, Precose
Intervention Description
Glucobay tablets on experimental day.
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Intervention Description
Placebo tablets on experimental day.
Intervention Type
Drug
Intervention Name(s)
Exendin (9-39)
Other Intervention Name(s)
Ex(9-39)
Intervention Description
Infusion of GLP-1 receptor antagonist as a study tool to block GLP-1 activity on experimental day.
Intervention Type
Drug
Intervention Name(s)
Placebo Saline
Intervention Description
9 mg/ml placebo saline infusion on experimental day.
Primary Outcome Measure Information:
Title
Plasma glucose
Description
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).
Time Frame
240 min

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Filip K Knop, MD, PhD
Organizational Affiliation
University Hospital, Gentofte, Copenhagen
Official's Role
Study Director
Facility Information:
Facility Name
Center for Diabetesresearch
City
Hellerup
ZIP/Postal Code
2900
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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