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.
Studieoversikt
Status
Intervensjon / Behandling
Studietype
Registrering (Faktiske)
Fase
- Ikke aktuelt
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Grunnvitenskap
- Tildeling: Randomisert
- Intervensjonsmodell: Crossover-oppdrag
- Masking: Dobbelt
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Aktiv komparator: 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
Andre navn:
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).
|
|
Placebo komparator: 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).
|
|
Aktiv komparator: 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
Andre navn:
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).
|
|
Placebo komparator: 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).
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
PPG-utflukter målt som inkrementelt areal under kurve (iAUC)
Tidsramme: -120,-45,-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutter
|
-120,-45,-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutter
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
forskjeller i magetømming, måling av s-paracetamol
Tidsramme: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutter
|
måling av tid til topp og inkrementelt areal under kurven (iAUC)
|
-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutter
|
|
hvileenergiforbruk (REE)
Tidsramme: -90,30,150 minutter
|
målt ved kalorimetri
|
-90,30,150 minutter
|
|
p-glukose mmol/L
Tidsramme: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutter
|
-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutter
|
|
|
food intake and appetite
Tidsramme: at time 0,30,60,90,120,150,180 minutes
|
assessed by a visual analogue scale (VAS)
|
at time 0,30,60,90,120,150,180 minutes
|
|
p-C-peptide pmol/l
Tidsramme: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
|
-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
|
|
|
glucagon, gastrin, cholecystokinin, GIP, GLP-1, oxyntomodulin
Tidsramme: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
|
-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
|
Samarbeidspartnere og etterforskere
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Filip K Knop, Assoc. Prof., Center for Diabetes Research, Gentofte Hospital, Kildegaardsvej 28, 2900 Hellerup, Denmark
Publikasjoner og nyttige lenker
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- H-15004078
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
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