The Impact of Lixisenatide on Postprandial Glucose Tolerance in Pancreatectomised Subjects (Px-Lixi)
The Impact of Lixisenatide on Postprandial Glucose Tolerance in Pancreatectomised Subjects -a Delineation of Extrapancreatic Effects
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.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Tipo di studio
Iscrizione (Effettivo)
Fase
- Non applicabile
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Scienza basilare
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione incrociata
- Mascheramento: Doppio
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Comparatore attivo: 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 |
single injection of 20 µg lixisenatide subcutaneously
Altri nomi:
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).
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Comparatore placebo: 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. |
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).
|
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Comparatore attivo: 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 |
single injection of 20 µg lixisenatide subcutaneously
Altri nomi:
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).
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Comparatore placebo: 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 |
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).
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Lasso di tempo |
|---|---|
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Escursioni PPG misurate come area sotto la curva incrementale (iAUC)
Lasso di tempo: -120,-45,-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minuti
|
-120,-45,-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minuti
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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differenze nello svuotamento gastrico, dosaggio dell's-paracetamolo
Lasso di tempo: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minuti
|
misurazione del tempo al picco e dell'area incrementale sotto la curva (iAUC)
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-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minuti
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dispendio energetico a riposo (REE)
Lasso di tempo: -90,30,150 minuti
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misurato con la calorimetria
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-90,30,150 minuti
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p-glucosio mmol/L
Lasso di tempo: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minuti
|
-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minuti
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food intake and appetite
Lasso di tempo: at time 0,30,60,90,120,150,180 minutes
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assessed by a visual analogue scale (VAS)
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at time 0,30,60,90,120,150,180 minutes
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p-C-peptide pmol/l
Lasso di tempo: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
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-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
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glucagon, gastrin, cholecystokinin, GIP, GLP-1, oxyntomodulin
Lasso di tempo: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
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-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
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Collaboratori e investigatori
Collaboratori
Investigatori
- Investigatore principale: Filip K Knop, Assoc. Prof., Center for Diabetes Research, Gentofte Hospital, Kildegaardsvej 28, 2900 Hellerup, Denmark
Pubblicazioni e link utili
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- H-15004078
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