Effects of Morbid Obesity and Bariatric Surgery on Brain Inflammation, Insulin Resistance and Activation of Central Reward System Studied Using PET- and MRI-imaging
试验速览
- 阶段
- 不适用
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Change in central inflammation
研究概览
简要总结
Background: Morbid obesity is associated with decreased brain µ-opioid receptor availability, possibly resulting in higher food intake needed to gain pleasure from eating. This decrease seems to normalize already 6 months after bariatric surgery, but the longer-term effects have not been studied. Obesity and insulin resistance result in significantly increased brain insulin-stimulated glucose uptake, whereas in every other tissue glucose uptake is lower. One possible explanation to this could be central inflammation and activation of brain glial cells, which has been shown to occur in animal models of obesity. Obesity has also been shown to associate with increased risk of Alzheimer's disease and cognitive decline in several studies.
Aims: The first objective of this study is to both study the effects of bariatric surgery as well as compare the effects of gastric bypass and sleeve gastrectomy on food-associated pleasure, extending the follow-up period to 2 years postoperatively. The second aim is to investigate the effect of morbid obesity and weight loss on brain inflammation and gliosis and its association with increased brain insulin-stimulated glucose uptake. Furthermore, association of obesity, insulin resistance, central inflammation and neurocognitive dysfunction are evaluated.
详细描述
Methods: A total of 60 morbidly obese subjects, 30 assigned for Roux-en-Y gastric bypass and 30 for sleeve gastrectomy according to routine treatment protocols will be recruited for this study. A control group of 30 healthy subjects will also be recruited. We will perform 1) structural MRI and MRS, 2) functional MRI during tasting and visual food cues, 3) PET imaging of µ-opioid receptor availability using [11C]-carfentanil, 4) PET imaging of cerebral inflammation and astrocyte activation using [11C]-PK11195, 5) measurement of whole-body and tissue insulin sensitivity by combining hyperinsulinemic, euglycemic clamp with [18F]-FDG-PET, 6) neuropsychological testing. The control group will only be studied once, whereas study procedures will be repeated for the morbidly obese before very-low calorie diet and 6, 12 and 24 months postoperatively.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（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
Change in central inflammation
时间窗: Controls: 0 months; Morbidly obese: preoperatively, 6 months postoperatively
Assessment of brain glial cell activation using \[11C\]-PK11195 tracer and positron emission tomography
次要结局
- Changes in brain μ-opioid receptor availability using PET imaging(Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months postoperatively)
- Changes in cognitive function studied with testing(Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months, 24 months postoperatively)
- Changes in tissue-specific insulin sensitivity using FDG-PET imaging(Controls: 0 months; Morbidly obese: preoperatively)
- Changes in central reward system using fMRI imaging(Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months, 24 months postoperatively)
- Changes in whole-body insulin sensitivity usign FDG-PET imaging(Controls: 0 months; Morbidly obese: preoperatively, 6 months postoperatively)
研究者
Pirjo Nuutila
professor
Turku University Hospital