The Impact of Lixisenatide on Postprandial Glucose Tolerance in Pancreatectomised Subjects

NCT02640118 | Completed

• 1 other identifier: H-15004078
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Diabetes After Total Pancreatectomy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• differences in gastric emptying, measurement of s-paracetamol

  -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes

• food intake and appetite

  at time 0,30,60,90,120,150,180 minutes

• resting energy expenditure (REE)

  -90,30,150 minutes

• 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

• 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

Study Arms (4)

Pancreatectomised + Lixisenatide

ACTIVE COMPARATOR

During the experimental day the patient will ingest a 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). Before the meal a Lixisenatide-injection will be given subcutaneously

Drug: Lixisenatide; Other: Standardized liquid meal

Pancreatectomized + lixisenatide-placebo

PLACEBO COMPARATOR

During the experimental day the patient will ingest a 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). Before the meal a placebo-injection will be given subcutaneously.

Drug: Lixisenatide-Placebo; Other: Standardized liquid meal

Healthy + Lixisenatide

ACTIVE COMPARATOR

During the experimental day the subject will ingest a 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). Before the meal a Lixisenatide-injection will be given subcutaneously

Drug: Lixisenatide; Other: Standardized liquid meal

Healthy + lixisenatide-placebo

PLACEBO COMPARATOR

During the experimental day the subject will ingest a 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). Before the meal a placebo-injection will be given subcutaneously

Drug: Lixisenatide-Placebo; Other: Standardized liquid meal

Interventions

Lixisenatide DRUG

single injection of 20 µg lixisenatide subcutaneously

Also known as: Lyxumia

Healthy + Lixisenatide; Pancreatectomised + Lixisenatide

Lixisenatide-Placebo DRUG

Healthy + lixisenatide-placebo; Pancreatectomized + lixisenatide-placebo

Standardized liquid meal OTHER

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).

Healthy + Lixisenatide; Healthy + lixisenatide-placebo; Pancreatectomised + Lixisenatide; Pancreatectomized + lixisenatide-placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Gentofte, Copenhagen: lead
• MCM Vaccines B.V.: collaborator

Related Publications (1)

• Juel CTB, Lund A, Andersen MM, Hansen CP, Storkholm JH, Rehfeld JF, van Hall G, Hartmann B, Wewer Albrechtsen NJ, Holst JJ, Vilsboll T, Knop FK. The GLP-1 receptor agonist lixisenatide reduces postprandial glucose in patients with diabetes secondary to total pancreatectomy: a randomised, placebo-controlled, double-blinded crossover trial. Diabetologia. 2020 Jul;63(7):1285-1298. doi: 10.1007/s00125-020-05158-9. Epub 2020 May 11.

  PMID: 32394228 DERIVED

MeSH Terms

Interventions

lixisenatide

Study Officials

• Filip K Knop, Assoc. Prof.

  Center for Diabetes Research, Gentofte Hospital, Kildegaardsvej 28, 2900 Hellerup, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associated Professor, MD, P.h.D.

Study Record Dates

• First Submitted: December 11, 2015
• First Posted: December 28, 2015
• Study Start: August 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: May 7, 2020

Record last verified: 2020-05