The Impact of Lixisenatide on Postprandial Glucose Tolerance in Pancreatectomised Subjects

NCT ID: NCT02640118

Last Updated: 2020-05-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2016-07-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Pancreatectomised + Lixisenatide

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

Group Type: ACTIVE_COMPARATOR

Lixisenatide

Intervention Type: DRUG

single injection of 20 µg lixisenatide subcutaneously

Standardized liquid meal

Intervention Type: 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).

Pancreatectomized + lixisenatide-placebo

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.

Group Type: PLACEBO_COMPARATOR

Lixisenatide-Placebo

Intervention Type: DRUG

Standardized liquid meal

Intervention Type: 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

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

Group Type: ACTIVE_COMPARATOR

Lixisenatide

Intervention Type: DRUG

single injection of 20 µg lixisenatide subcutaneously

Standardized liquid meal

Intervention Type: 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-placebo

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

Group Type: PLACEBO_COMPARATOR

Lixisenatide-Placebo

Intervention Type: DRUG

Standardized liquid meal

Intervention Type: 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).

Interventions

Lixisenatide

single injection of 20 µg lixisenatide subcutaneously

Intervention Type: DRUG

Lixisenatide-Placebo

Intervention Type: DRUG

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).

Intervention Type: OTHER

Other Intervention Names

Lyxumia

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

MCM Vaccines B.V.

INDUSTRY

Sponsor Role: collaborator

University Hospital, Gentofte, Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Filip Krag Knop

Associated Professor, MD, P.h.D.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Filip K Knop, Assoc. Prof.

Role: PRINCIPAL_INVESTIGATOR

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

References

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.

Reference Type: DERIVED

PMID: 32394228 (View on PubMed)

Other Identifiers

H-15004078

Identifier Type: -

Identifier Source: org_study_id