Characterization of Human Intestinal Macrophages in Metabolic Disease - iMAC (Pilot) Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Type and rate of subpopulations of intestinal macrophages
研究概览
简要总结
This is a prospective, observational study aiming at improving the understanding of the pathophysiology of metabolic disease. As inflammation has been recognized as a key characteristic of metabolic disease but its starting point is still unknown, the investigators' aim is to characterize intestinal macrophages from human gut biopsies taken in diagnostic endoscopies of the gastrointestinal tract or in bariatric surgeries for clinical reasons.
详细描述
Metabolic disease including obesity and diabetes has reached epidemic proportions in the past years. Besides classical risk factors such as unhealthy diet and physical inactivity, smoking and air pollution have also emerged as unexpected risk factors for type 2 Diabetes.
Inflammation has been reported as key characteristic of metabolic disease and is predictive of future cardiovascular events. However, the starting point of chronic low-grade inflammation is not known.
As the gastrointestinal tract first comes into contact with dietary components, but potentially also air pollution/ smoke particles ingested upon mucociliary clearance from the lung, the gut could be the starting point of inflammation in metabolic disease.
The aim of this study is to characterize intestinal macrophages in obese versus lean subjects and smokers versus non-smokers to translate the principal investigator's preclinical findings to human disease and assess whether an inflammatory shift prevails in human intestinal macrophages in metabolic disease. Additionally, to assess whether intestinal macrophage subpopulations can be altered deliberately by nutritional intervention, the investigators will assess intestinal macrophages from subjects scheduled for bariatric surgery that will be on a calorie-restricted diet during the last 2 to 4 weeks prior to surgery.
The macrophages originate from human gut samples. As patients will undergo diagnostic endoscopy of the gastrointestinal tract or bariatric surgery for clinical reasons and the standard of care will not be changed by the study, there will be no additional interventions to patients by their participation in the study. Additionally, three EDTA and one serum blood tube for the analysis of inflammatory cells and markers in the blood will be taken as well as a single stool sample. The investigators' goal is to recruit in total 150 patients as it will be a pilot study in a first step.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patient undergoing colonoscopy:
- •Obese (BMI > 32 kg/m2 ) and smoker (≥ 1 pack cigarettes/d)
- •Obese (BMI > 32 kg/m2 ) and non-smoker (control group)
- •Lean (BMI < 27 kg/m2 ) and smoker (≥ 1 pack cigarettes/d)
- •Lean (BMI < 27 kg/m2 ) and non-smoker (control group)
- •Patient undergoing gastroscopy:
- •Obese (BMI > 35 kg/m2 ) and non-smoker planned for bariatric surgery
- •Lean (BMI < 27 kg/m2 ) and non-smoker (control group)
排除标准
- •Inability to provide informed consent, e.g. mental impairment or insufficient knowledge of project language
- •Intake of corticosteroids
- •Anti-inflammatory/ immunosuppressive drugs
- •Clinical signs of current infection
- •Known anemia (e.g. hemoglobin < 110 g/L for males, < 100 g/L for females)
- •Known neutropenia (e.g. leukocyte count < 1.5 × 10^9/L or ANC < 0.5 × 10^9/L)
- •Known immunodeficiency, e.g. HIV
- •Known vasculitis, collagenosis
- •Known inflammatory bowel disease
- •Known adrenal insufficiency and/or substitution with glucocorticoids
- •Known clinically significant kidney or liver disease (e.g. creatinine > 1.5 mg/dL, AST/ALT > 2 × ULN, alkaline phosphatase > 2 × ULN, or total bilirubin [tBili] > 1.5 × ULN)
- •Risky daily alcohol consumption (> 24g/d for males, > 12g for females), known liver cirrhosis Child B or C
- •Known uncontrolled congestive heart failure
- •Known uncontrolled malignant disease
- •Currently pregnant or breastfeeding
结局指标
主要结局
Type and rate of subpopulations of intestinal macrophages
时间窗: 2 years
Quality (inflammatory versus non-inflammatory subpopulations) of intestinal macrophages in biopsies from the gastrointestinal tract in obese versus lean subjects and smokers versus non-smokers measured with flow cytometry.
Number of intestinal macrophages
时间窗: 2 years
Quantity (absolute and relative numbers) of intestinal macrophages in biopsies from the gastrointestinal tract in obese versus lean subjects and smokers versus non-smokers measured with flow cytometry.
次要结局
- Type and rate of subpopulations of other intestinal immune cells(2 years)
- Gene expression profile of intestinal macrophages(2 years)
- Number of other intestinal immune cells(2 years)
研究者
Claudia Cavelti
private lecturer
University Hospital, Basel, Switzerland