Response to Glucagon in Patients With Metabolic-associated Steatotic Liver Disease: a Feasibility Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 20
- 主要终点
- Standard deviation of glucose turnover
研究概览
简要总结
One in four adults worldwide have too much fat stored in the liver which is known as metabolic associated steatotic liver disease (MASLD). This was previously known as non- alcoholic fatty liver disease (NAFLD). This can lead to liver failure and death in severe cases. Unfortunately, there are no specific drugs to treat MASLD.
Glucagon is a natural hormone that controls how the body stores and uses fuel. Glucagon acts on liver cells to use protein and fat to make sugar. It decreases the amount of liver fat.
The investigators think that patients with MASLD may not respond to the actions of glucagon. This could contribute to the build-up of fat in the liver.
In this study the investigators will be investigating the effects of glucagon on protein breakdown and sugar production in patients with and without MASLD.
Healthy volunteers and patients with MASLD will attend for one study visit each which will last for 4-5 hours. During this time they will have infusions into a vein of glucagon and other hormones, amino acids (to mimic the fed state) and 'tracers'. From another vein they will have several blood samples during this period. By analysing these blood samples the investigators will be able to measure the effects of glucagon on protein and glucose turnover (metabolism), and whether this differs between healthy volunteers and those with MASLD.
If the investigators find that patients with MASLD are resistant to the actions of glucagon, this could help with the development of drugs to treat MASLD.
详细描述
This is a feasibility cohort-control experimental medicine study. Participants will attend for one study visit lasting 4-5 hours. The study will involve a maximum of 10 healthy volunteers and 10 patients with MASLD. All subjects will undergo an amino acid infusion and pancreatic clamp during which they will have stable isotope turnover of glucose and alanine measured in two steady state periods - firstly, with low-dose glucagon infusion and secondly, with high-dose glucagon infusion. The studies will take place in the Clinical Research Unit at Hammersmith Hospital, Imperial College.
Screening visit:
During this visit that will last around an hour, prospective participants will have a consultation with a study doctor. The doctor will assess medical history and explain the study. They will also perform a routine physical examination and take some blood tests. Women of child-bearing age will undergo urinalysis to exclude pregnancy. Participants will be contacted a couple of days later to let discuss blood test results, and if these are satisfactory they will be invited to attend for 1 study visit.
Study visit:
Participants will be asked to avoid alcohol and strenuous exercise for 24 hours before the study visit. They will be asked to fast (that is, consume nothing except water) for 10-14 hours before the visit. The visits will start at around 8 or 9am and finish at about 1 or 2pm.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Standard deviation of glucose turnover
时间窗: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Standard deviation of differences in glucose turnover between two steady state periods (low and high dose glucagon infusion) for use in a subsequent sample size calculation
Standard deviation of alanine turnover
时间窗: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Standard deviation of differences in alanine turnover between two steady state periods (low and high dose glucagon infusion) for use in a subsequent sample size calculation
次要结局
- Plasma free fatty acids(one study visit = 1 day per volunteer, 20 study visits, 3 months in total)
- Urine metabolite composition(one study visit = 1 day per volunteer, 20 study visits, 3 months in total)
- Plasma lipid composition(one study visit = 1 day per volunteer, 20 study visits, 3 months in total)
- Urine lipid composition(one study visit = 1 day per volunteer, 20 study visits, 3 months in total)
- Plasma lactate(one study visit = 1 day per volunteer, 20 study visits, 3 months in total)
- Plasma metabolite composition(one study visit = 1 day per volunteer, 20 study visits, 3 months in total)
- Plasma glucagon(one study visit = 1 day per volunteer, 20 study visits, 3 months in total)
- Plasma insulin(one study visit = 1 day per volunteer, 20 study visits, 3 months in total)
- Plasma total amino acids(one study visit = 1 day per volunteer, 20 study visits, 3 months in total)
- Plasma urea(one study visit = 1 day per volunteer, 20 study visits, 3 months in total)
- Microbiome composition of stool(one study visit = 1 day per volunteer, 20 study visits, 3 months in total)