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The Impact of Lixisenatide on Postprandial Glucose Tolerance in Pancreatectomised Subjects (Px-Lixi)

6. maj 2020 opdateret af: Filip Krag Knop, University Hospital, Gentofte, Copenhagen

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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

24

Fase

  • Ikke anvendelig

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 80 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ja

Køn, der er berettiget til at studere

Alle

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

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Grundvidenskab
  • Tildeling: Randomiseret
  • Interventionel model: Crossover opgave
  • Maskning: Dobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / 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
Medicin: Lixisenatide
single injection of 20 µg lixisenatide subcutaneously
Andre navne:
  • Lyxumia
Andet: 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).
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.
Andet: 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).
Medicin: Lixisenatide-Placebo
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
Medicin: Lixisenatide
single injection of 20 µg lixisenatide subcutaneously
Andre navne:
  • Lyxumia
Andet: 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).
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
Andet: 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).
Medicin: Lixisenatide-Placebo

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Tidsramme
PPG-udflugter målt som trinvis 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
Foranstaltningsbeskrivelse
Tidsramme
forskelle i mavetømning, måling af 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 af tid til top og trinvis 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
hvileenergiforbrug (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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

University Hospital, Gentofte, Copenhagen

Samarbejdspartnere

MCM Vaccines B.V.

Efterforskere

  • Ledende efterforsker: Filip K Knop, Assoc. Prof., Center for Diabetes Research, Gentofte Hospital, Kildegaardsvej 28, 2900 Hellerup, Denmark

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. august 2015

Primær færdiggørelse (Faktiske)

1. juli 2016

Studieafslutning (Faktiske)

1. juli 2016

Datoer for studieregistrering

Først indsendt

11. december 2015

Først indsendt, der opfyldte QC-kriterier

21. december 2015

Først opslået (Skøn)

28. december 2015

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

7. maj 2020

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

6. maj 2020

Sidst verificeret

1. maj 2020

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • H-15004078

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

UBESLUTET

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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