The Effect of GLP-1 on Postprandial Glucagon Secretion Independent of The Gastric Emptying Rate (ALFA-1)

The Effect of GLP-1 on Postprandial Glucagon Secretion During Prolonged and Intermittent Stimulation of the GLP-1 Receptor Independent of The Gastric Emptying Rate. A Randomized, Open-label Study in People With Type 1 Diabetes

Aim: To investigate the glucagonostatic effect of glucagon-like peptide-1 (GLP-1) independent of the gastric emptying rate.

Study Overview

• Status: Unknown
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Liraglutide; Drug: Exenatide; Procedure: Liquid meal test; Other: No drug (Baseline day)

Detailed Description

Aim: To investigate the glucagonostatic effects of glucagon-like peptide-1 (GLP-1) during prolonged and intermittent stimulation of the GLP-1 receptor independent of the gastric emptying rate. Glucagon concentrations will be measured following a liquid meal administered in duodenum at baseline and after exenatide, and liraglutide treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 1 Diabetes
• >18 years
• No residual beta-cell function (stimulated C-peptide < 60 pmol)

Exclusion Criteria:

• Pancreatitis
• gastroparesis
• history of alcohol and/or drug abuse
• pregnancy and lactation
• other medical or psychological condition that made the patient unsuitable for study participation according to the investigators´ assessment
• contraindications to gastroscopy
• cancer (unless in complete remission > five years)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liraglutide + Liquid meal test; Liraglutide 1.2 mg once daily for 14 days (0.6 mg/day for one week, escalated to 1.2 mg/day after one week)	Drug: Liraglutide; Procedure: Liquid meal test
Experimental: Exenatide + Liquid meal test; Exenatide 10 mcg twice daily for 14 days (5 mcg twice daily for one week, escalated to 10 mcg twice daily after one week)	Drug: Exenatide; Procedure: Liquid meal test
Other: Baseline + Liquid meal test; Baseline day with no additional medication	Procedure: Liquid meal test; Other: No drug (Baseline day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucagon concentration (postprandial)	glucagon area under the curve (AUC) (0-240 minutes) and baseline to peak increments will be calculated	4 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial glucose concentrations	glucose AUC (0-240 minutes) and baseline to peak increments will be calculated	4 hours
glucagon-like peptide-1 (GLP-1)	GLP-1 AUC (0-240 minutes) and baseline to peak increments will be calculated	4 hours
glucagon-like peptide-2 (GLP-2)	GLP-2 AUC (0-240 minutes) and baseline to peak increments will be calculated	4 hours
glucose-dependent insulinotropic polypeptide (GIP)	GIP AUC (0-240 minutes) and baseline to peak increments will be calculated	4 hours
Cholecystokinin (CCK)	CCKAUC (0-240 minutes) and baseline to peak increments will be calculated	4 hours
Peptide YY (PYY)	PYY AUC (0-240 minutes) and baseline to peak increments will be calculated	4 hours
Ghrelin	Ghrelin AUC (0-240 minutes) and baseline to peak increments will be calculated	4 hours
Gastrin	Gastrin AUC (0-240 minutes) and baseline to peak increments will be calculated	4 hours
Oxyntomodulin	Oxyntomodulin AUC (0-240 minutes) and baseline to peak increments will be calculated	4 hours
Free fatty acids (FFA)	FFA AUC (0-240 minutes) and baseline to peak increments will be calculated	4 hours
triacylglycerol (TAG)	TAG AUC (0-240 minutes) and baseline to peak increments will be calculated	4 hours

Collaborators and Investigators

• Sponsor: Hvidovre University Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Anticipated): November 1, 2015

Study Registration Dates

• First Submitted: August 6, 2015
• First Submitted That Met QC Criteria: October 21, 2015
• First Posted (Estimate): October 22, 2015

Study Record Updates

• Last Update Posted (Estimate): October 22, 2015
• Last Update Submitted That Met QC Criteria: October 21, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Incretins; Glucagon; Glukagon-like peptide-1 (GLP-1); GLP-1 receptor agonist (GLP-1RA)
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Liraglutide; Exenatide
• Other Study ID Numbers: H-3-2014-128