Исследование GAPSID: как аналоги GLP-1 предотвращают стероид-индуцированный диабет
Как аналоги GLP-1 предотвращают диабет, вызванный стероидами
TITLE: How GLP-1 Analogues prevent steroid-induced diabetes (The GAPSID Study)
DESIGN: A double-blind study evaluating how GLP-1 analogues, compared with metformin, prevent hyperglycaemia in response to a 7-day course of dexamethasone (DEX) 6 mg once daily. This is a mechanistic experimental medicine study.
AIMS: To evaluate the mechanisms by which GLP-1 analogues reduce steroid-induced hyperglycaemia compared to metformin.
OUTCOME MEASURES:
- Primary: Glucose tolerance in response to standardised mixed meal test (MMT) lasting for 240 minutes, measured in all participants at baseline and on day 7 DEX.
- Secondary: Indices of insulin resistance (M-value), beta-cell function (acute insulin response to glucose) and disposition, as measured by a combined IV glucose tolerance test and hyperinsulinaemic-euglycaemic clamp, performed at baseline and on day 7 DEX.
- Exploratory: Tissue specific changes in adipose AMPK determined from adipose and muscle biopsies, taken from a subset of approximately 8 individuals in each group.
ELIGIBILITY: People living with pre-diabetes or lifestyle controlled diabetes
STUDY DURATION: This study will take place over 3 weeks for each partcipant. Study procedures include 10 days of baseline continuous glucose monitoring (CGM) followed by 7 days of dexamethasone with GLP-1, metformin or placebo. Participants will attend a follow-up visit 3-5 days after completing the 7-day course of study drug. The study will run over a period of 3 years.
ANTICIPATED IMPACT: Mechanistic evidence for the use of GLP-1 analogues, compared with metformin, in the treatment of steroid-induced diabetes.
Обзор исследования
Статус
Вмешательство/лечение
Тип исследования
Регистрация (Оцененный)
Фаза
- Непригодный
Контакты и местонахождение
Контакты исследования
- Имя: Katharine Lazarus, MBChB, BSc
- Номер телефона: 07555717544
- Электронная почта: k.lazarus@imperial.ac.uk
Места учебы
-
-
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London, Соединенное Королевство
- Рекрутинг
- Imperial College Healthcare NHS Trust
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-
Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
Принимает здоровых добровольцев
Полы, имеющие право на обучение
Описание
Inclusion Criteria:
- Adults ≥ 18 years;
- Male or female;
- Pre-diabetes (HbA1c ≥42 and <47 mmol/mol, or lifestyle-controlled diabetes (HbA1c ≥48 and ≤52 mmol/mol); measurements within range on two separate occasions ≥90 days apart)
- Body mass index ≥22.5 kg/m2
Exclusion Criteria:
- Prior treatment with any diabetes medication within 90 days;
- Current or planned pregnancy, or current breastfeeding;
- Previous treatment with GC (topical, oral, injected) within 30 days or 90 days for extended-release injected GCs (e.g. Depo-Medrone);
- Continuing requirement for GC treatment (e.g. for steroid replacement, chronic inflammatory or immunological condition);
- Treatment with medications altering DEX pharmacokinetics (e.g. phenytoin, carbamazepine, ritonavir).
- History of pancreatitis, renal disease (eGFR <30), severe hepatic impairment, gallbladder disorders, or GI disease (e.g. IBD), heart failure, history of medullary thyroid cancer (MTC), or previous skin reactions.
- History of bleeding disorders of anticoagulant therapies (exclusion from the biopsy substudy only)
- History of giving blood or having taken part in another non-related study in the last three months
- History of any other medical, psychological condition, or use of any medications, which, in the opinion of the investigators, would either interfere with the study or compromise the safety of the participant.
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Фундаментальная наука
- Распределение: Рандомизированный
- Интервенционная модель: Параллельное назначение
- Маскировка: Четырехместный
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
|
Экспериментальный: Once daily semaglutide
Once daily semaglutide 3 mg (uptitrated to 3 mg twice daily after two days). |
Oral semaglutide 3mg once uptitrated to twice daily |
|
Активный компаратор: - Metformin
Metformin modified release tablets (500mg once daily for the first two days, then 500 mg twice daily). |
Metformin modified release tablets 500mg once daily uptitrated to twice daily). |
|
Плацебо Компаратор: Placebo
Placebo tablets |
Placebo tablets |
Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Difference in Glucose tolerance
Временное ограничение: Through study completion, on day 7 dexamethasone and study medication
|
Glucose tolerance as measured by glucose area under the curve (AUC), in response to standardised mixed meal test (MMT) lasting for 240 minutes. This will be measured in all participants at baseline and at the end of the study medication period (after 7 days of dexamethasone and study medication). |
Through study completion, on day 7 dexamethasone and study medication
|
Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Difference in insulin secretion
Временное ограничение: Day 6 of dexamethasone and study medication
|
This will be measured by the acute insulin response to glucose based on the incremental AUC for insulin during the first 10 minutes of an IVGTT and the second phase insulin response based on incremental AUC for insulin during +10 to +60 minutes. This will be measured in a subset of patients (10 from each randomisation group), performed at baseline and on day 6 of dexamethasone and study medication |
Day 6 of dexamethasone and study medication
|
|
Difference in insulin sensitivity
Временное ограничение: Day 6
|
This will be measured by the M value, based on the glucose infusion rate during the last 60 minutes of a hyperinsulinaemic-euglycaemic clamp. This will be measured in a subset of patients (10 from each randomisation group), performed at baseline and on day 6 of dexamethasone and study medication |
Day 6
|
|
Difference in insulin sensitivity
Временное ограничение: Day 6
|
This will be measured by the M/I index, calculated by the M value divided by the mean steady state insulin levels during the last 60 minutes of a hyperinsulinaemic-euglycaemic clamp. This will be measured in a subset of patients (10 from each randomisation group), performed at baseline and on day 6 of dexamethasone and study medication |
Day 6
|
|
Difference in insulin sensitivity
Временное ограничение: Day 6
|
This will be measured by the disposition index. This will be calculated as the product of the AIRg and M value during the combined IVGTT and hyperinsulinaemic-euglycaemic clamp. This will be measured in a subset of patients (10 from each randomisation group), performed at baseline and on day 6 of dexamethasone and study medication. |
Day 6
|
Другие показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Mean glucose and glycaemic variation by continuous glucose monitoring (CGM), using a validated blinded system (Dexcom G7).
Временное ограничение: Through study completion
|
A baseline recording will be made for 10 days prior to DEX. A second 10-day recording will be made covering the 7 days of DEX and for 3 days after. |
Through study completion
|
|
Changes in fasting gut hormones
Временное ограничение: Through study completion, on day 7 dexamethasone and study medication
|
Fasting glucose will be measured at baseline and after a 7-day course of DEX and treatment intervention. |
Through study completion, on day 7 dexamethasone and study medication
|
|
Changes in fasting gut hormones
Временное ограничение: Through study completion, on day 7 dexamethasone and study medication
|
Fasting insulin and c-peptide levels will be measured at baseline and after a 7-day course of DEX and treatment intervention. |
Through study completion, on day 7 dexamethasone and study medication
|
|
Changes in fasting gut hormones
Временное ограничение: Through study completion, on day 7 dexamethasone and study medication
|
Fasting glucagon levels will be measured at baseline and after a 7-day course of DEX and treatment intervention. |
Through study completion, on day 7 dexamethasone and study medication
|
|
Changes in fasting lipid profile
Временное ограничение: Through study completion, on day 7 dexamethasone and study medication
|
Fasting lipid profiles will be measured at baseline and after a 7-day course of DEX and treatment intervention. |
Through study completion, on day 7 dexamethasone and study medication
|
|
Changes in post prandial gut hormones
Временное ограничение: Through study completion, on day 7 dexamethasone and study medication
|
Post prandial insulin and c-peptide levels will be measured during the mixed meal test, performed at baseline and after a 7-day course of DEX and treatment intervention. |
Through study completion, on day 7 dexamethasone and study medication
|
|
Changes in post prandial gut hormones
Временное ограничение: Through study completion, on day 7 dexamethasone and study medication
|
Post prandial glucagon levels will be measured during the mixed meal test, performed at baseline and after a 7-day course of DEX and treatment intervention. |
Through study completion, on day 7 dexamethasone and study medication
|
|
Changes in anthropometrics
Временное ограничение: Through study completion, on day 7 dexamethasone and study medication
|
Anthropometric measurements of height and weight will be combined to report BMI kg/m2 before and after a 7-day course of DEX and treatment intervention. |
Through study completion, on day 7 dexamethasone and study medication
|
|
Changes in anthropometrics
Временное ограничение: Through study completion, on day 7 dexamethasone and study medication
|
Measurements of hip and waist circumference will be combined to calculate the waist:hip ratio before and after a 7-day course of DEX and treatment intervention. |
Through study completion, on day 7 dexamethasone and study medication
|
|
Tissue specific changes in AMPK determined from adipose and muscle biopsies
Временное ограничение: Through study completion, on day 7 dexamethasone and study medication
|
This will be taken from a subset of approximately 8 individuals in each group prior to, and at the end of a 7 day course of DEX. Depending on emerging data and participant uptake, this may be subject to change. |
Through study completion, on day 7 dexamethasone and study medication
|
Соавторы и исследователи
Спонсор
Следователи
- Главный следователь: Karim Meeran, Imperial College London
Даты записи исследования
Изучение основных дат
Начало исследования (Действительный)
Первичное завершение (Оцененный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
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
- 22HH8018
Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
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