The Impact of Lixisenatide on Postprandial Glucose Tolerance in Pancreatectomised Subjects

Diabetes After Total Pancreatectomy Clinical Trial

— Px-Lixi  

Official title:

The Impact of Lixisenatide on Postprandial Glucose Tolerance in Pancreatectomised Subjects -a Delineation of Extrapancreatic Effects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02640118
• Other study ID #: H-15004078
• Status: Completed
• Phase: N/A
• Start date: August 2015
• Est. completion date: July 2016

Study information

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

Clinical Trial Summary

Postprandial glucose (PPG) excursions are not only determined by insulin-mediated glucose disposal and endogenous glucose production (regulated by insulin and glucagon); also the rate of gastric emptying constitutes an important determinant of PPG levels 1. The short-acting glucagon-like peptide-1 (GLP-1) receptor agonist lixisenatide is used in the treatment of type 2 diabetes. It increases glucose-dependent insulin secretion, suppresses glucagon secretion and reduces gastric emptying of meals 2. These three mechanisms most likely constitute the weightiest mechanisms behind the potent impact of lixisenatide on exaggerated PPG excursions in patients with type 2 diabetes - which often are normalised during lixisenatide treatment 3. However, the separate impact of lixisenatide-induced reduction of gastric emptying (independently of the pancreatic effects) has been difficult to determine. Importantly, treatment with lixisenatide also decreases appetite and food intake and may, like native GLP-1, increase energy expenditure 4. So far an exact demarcation of the pancreatic and extrapancreatic effects of lixisenatide in humans remains to be established.

The present project serves to determine whether effects of lixisenatide on gastric emptying, appetite, food intake and resting energy expenditure are dependent on the endocrine pancreas.

The study is a randomised, placebo-controlled, double-blinded, cross-over study.

12 healthy persons and 12 pancreatectomized patients (i.e. patients who have had their pancreata removed due to pancreatic cancer or severe chronic pancreatitis) will be subjected to two experimental days on which they will undergo a liquid meal test followed by a fasting period and finished off with an ad libitum meal with lixisenatide and placebo, respectively.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion criteria Pancreatectomised patients

• Caucasians above 18 years of age who have undergone total pancreatectomy

• Normal haemoglobin

• Informed consent Healthy subjects

• Normal fasting plasma glucose (FPG) and normal HbA1C (according to the World Health Organization (WHO) criteria)

• Normal haemoglobin

• Age above 18 years

• Informed consent

Exclusion criteria Pancreatectomised patients

• Inflammatory bowel disease

• Operation within the last 3 months

• Ongoing chemotherapy or chemotherapy within the last 3 months

• Ostomy

• Nephropathy (serum creatinine >150 µM and/or albuminuria)

• Severe liver disease (serum alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >3×normal values)

• Pregnancy and/or breastfeeding

• Age above 80 years

• Any condition that the investigator feels would interfere with trial participation Healthy subjects

• Diabetes mellitus (DM)

• Prediabetes (impaired glucose tolerance and/or impaired FPG)

• First degree relatives with DM

• Inflammatory bowel disease

• Intestinal resection and/or ostomy

• Nephropathy (serum creatinine >150 µM and/or albuminuria

• Liver disease (ALAT and/or serum ASAT >2×normal values)

• Pregnancy and/or breastfeeding

• Age above 80 years

• Any condition that the investigator feels would interfere with trial participation

Related Conditions & MeSH terms

• Diabetes After Total Pancreatectomy

Intervention

Drug:
• Lixisenatide
single injection of 20 µg lixisenatide subcutaneously
• Lixisenatide-Placebo

Other:
• Standardized liquid meal
standardized liquid meal (200 ml containing 1,650 kJ (394 kcal): carbohydrate 50%, protein 15%, fat 35%, consisting of glucose (48.4 g + 1.6 g [U-13C6]-glucose), rapeseed oil (14.1 g), whey protein (15.2 g) and 1.5 g paracetamol).

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Gentofte, Copenhagen	MCM Vaccines B.V.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PPG excursions measured as incremental area under curve (iAUC)		-120,-45,-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
Secondary	differences in gastric emptying, measurement of s-paracetamol	measurement of time to peak and incremental area under the curve (iAUC)	-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
Secondary	food intake and appetite	assessed by a visual analogue scale (VAS)	at time 0,30,60,90,120,150,180 minutes
Secondary	resting energy expenditure (REE)	measured by calorimetry	-90,30,150 minutes
Secondary	p-glucose mmol/L		-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
Secondary	p-C-peptide pmol/l		-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
Secondary	glucagon, gastrin, cholecystokinin, GIP, GLP-1, oxyntomodulin		-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes