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.
Обзор исследования
Статус
Вмешательство/лечение
Тип исследования
Регистрация (Действительный)
Фаза
- Непригодный
Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
Принимает здоровых добровольцев
Полы, имеющие право на обучение
Описание
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
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Фундаментальная наука
- Распределение: Рандомизированный
- Интервенционная модель: Назначение кроссовера
- Маскировка: Двойной
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
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Активный компаратор: 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
Другие имена:
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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Плацебо Компаратор: 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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Активный компаратор: 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
Другие имена:
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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Плацебо Компаратор: 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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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Временное ограничение |
|---|---|
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Экскурсии PPG, измеренные как приращение площади под кривой (iAUC)
Временное ограничение: -120,-45,-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 минут
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-120,-45,-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 минут
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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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различия в опорожнении желудка, измерение s-парацетамола
Временное ограничение: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 минут
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измерение времени до пика и дополнительной площади под кривой (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 минут
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Расход энергии в покое (REE)
Временное ограничение: -90,30,150 минут
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измеряется калориметрическим методом
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-90,30,150 минут
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р-глюкоза ммоль/л
Временное ограничение: -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 минут
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-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 минут
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food intake and appetite
Временное ограничение: 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
Временное ограничение: -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
Временное ограничение: -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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Соавторы и исследователи
Соавторы
Следователи
- Главный следователь: Filip K Knop, Assoc. Prof., Center for Diabetes Research, Gentofte Hospital, Kildegaardsvej 28, 2900 Hellerup, Denmark
Публикации и полезные ссылки
Даты записи исследования
Изучение основных дат
Начало исследования
Первичное завершение (Действительный)
Завершение исследования (Действительный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Оценивать)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Дополнительные соответствующие термины MeSH
Другие идентификационные номера исследования
- H-15004078
Планирование данных отдельных участников (IPD)
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