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Trial record 5 of 61 for:    Lixisenatide

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

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ClinicalTrials.gov Identifier: NCT02640118
Recruitment Status : Completed
First Posted : December 28, 2015
Last Update Posted : June 21, 2019
Sponsor:
Collaborator:
MCM Vaccines B.V.
Information provided by (Responsible Party):
Filip Krag Knop, University Hospital, Gentofte, Copenhagen

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.


Condition or disease Intervention/treatment Phase
Diabetes After Total Pancreatectomy Drug: Lixisenatide Drug: Lixisenatide-Placebo Other: Standardized liquid meal Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: The Impact of Lixisenatide on Postprandial Glucose Tolerance in Pancreatectomised Subjects -a Delineation of Extrapancreatic Effects
Study Start Date : August 2015
Actual Primary Completion Date : July 2016
Actual Study Completion Date : July 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: 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

Drug: Lixisenatide
single injection of 20 µg lixisenatide subcutaneously
Other Name: Lyxumia

Other: 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 Comparator: 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.

Drug: Lixisenatide-Placebo
Other: 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).

Active Comparator: 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

Drug: Lixisenatide
single injection of 20 µg lixisenatide subcutaneously
Other Name: Lyxumia

Other: 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 Comparator: 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

Drug: Lixisenatide-Placebo
Other: 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).




Primary Outcome Measures :
  1. PPG excursions measured as incremental area under curve (iAUC) [ Time Frame: -120,-45,-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes ]

Secondary Outcome Measures :
  1. differences in gastric emptying, measurement of s-paracetamol [ Time Frame: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes ]
    measurement of time to peak and incremental area under the curve (iAUC)

  2. food intake and appetite [ Time Frame: at time 0,30,60,90,120,150,180 minutes ]
    assessed by a visual analogue scale (VAS)

  3. resting energy expenditure (REE) [ Time Frame: -90,30,150 minutes ]
    measured by calorimetry

  4. p-glucose mmol/L [ Time Frame: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes ]
  5. p-C-peptide pmol/l [ Time Frame: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes ]
  6. glucagon, gastrin, cholecystokinin, GIP, GLP-1, oxyntomodulin [ Time Frame: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02640118


Sponsors and Collaborators
University Hospital, Gentofte, Copenhagen
MCM Vaccines B.V.
Investigators
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Principal Investigator: Filip K Knop, Assoc. Prof. Center for Diabetes Research, Gentofte Hospital, Kildegaardsvej 28, 2900 Hellerup, Denmark

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Responsible Party: Filip Krag Knop, Associated Professor, MD, P.h.D., University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier: NCT02640118     History of Changes
Other Study ID Numbers: H-15004078
First Posted: December 28, 2015    Key Record Dates
Last Update Posted: June 21, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
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Acetaminophen
Lixisenatide
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antipyretics
Hypoglycemic Agents