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The Endocrine Secretome After Gastric Bypass Surgery

2017年3月21日 更新者:Filip Krag Knop

Searching for Altered Gene Expression in the Endocrine Secretome Following Roux-en-Y Gastric Bypass Surgery

Examination of the molecular phenotype and composition of endocrine cells in the gastrointestinal tract correlated to analyses of blood for hormones/analytes before and after Roux-en-Y gastric bypass surgery in morbidly obese individuals both with and without type 2 diabetes

研究概览

详细说明

Enteroscopy was conducted during sedation with Propofol®. The pre-surgical sampling included biopsies retrieved from the stomach and at the expected site of anastomosis. During RYGB surgery, a ~1 cm gut tissue sample was removed at the site of anastomosis. The post-surgical enteroscopy ~3 months after RYGB surgery included biopsies taken from the gastric pouch, the alimentary limb, the biliopancreatic limb and common channel. One sample from each location was immersion-fixated in formalin for subsequent histological analyses and one sample was placed in a tube with RNA-preserving media for mRNA expression analysis. Remaining samples were snap-frozen and stored at -80°C until further processing.

Enteroendocrine cells were identified and isolated from biopsies obtained at several sites in the small intestine by using immunohistochemistry and laser capture technology. Isolated individual enteroendocrine cells were extensively characterised by next generation sequencing (Illumina NGS).

The participants also went through four mixed meal tests with blood sampling performed: before an 8 % diet-induced weight loss was initiated and one week before/one week after/3 months after RYGB surgery. Blood was sampled at several specific time points.

The plasma, serum and urine collected from study participants before and after RYGB surgery will be analysed for biomarkers/analytes and correlated with clinical data (weight, BMI, waist/hip ratio, blood pressure) and molecular phenotype found in gut samples.

To study changes in gut bacteria (microbiota) composition stool samples were collected during the study and will be analysed for microbiota composition by means of bacterial DNA sequencing.

研究类型

介入性

注册 (实际的)

28

阶段

  • 不适用

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 60年 (成人)

接受健康志愿者

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Obese subjects referred for assessment of eligibility for RYGB surgery
  • Age ≥25 and ≤ 60 years
  • Able to understand written patient information and obtained signed informed consent
  • Type 2 diabetes patients treated with lifestyle, metformin and/or sulfonylurea will be allowed participation.

Exclusion Criteria:

  • Diagnosis of diabetes mellitus type 1
  • Individuals being categorized as subjects with type 2 diabetes according to ADA 2014 criteria AND currently being treated with DPPIV inhibitors, GLP-1 agonists, insulin and/or SGLT2 inhibitors.
  • Co-morbidities that, in the discretion of the investigators, exclude study participation such as chronic obstructive pulmonary disease (COPD) stage III, significant cardiac arrhythmias etc.
  • Previous gastrointestinal surgery (excluding cholecystectomy and appendectomy).
  • Gastrointestinal conditions making the subject unsuitable to participate in the study such as ulcerative colitis, Crohn´s disease, clinically significant food allergies, candidiasis etc.
  • Chronic systemic inflammatory diseases (e.g,. rheumatoid arthritis) and other conditions significantly affecting inflammation status or immunoregulation (severe allergies, status post transplantation etc.)
  • Chronic, planned or likely-to-be-required parenteral or oral corticosteroid medication during the study period, or (parenteral or oral) corticosteroid medication <4 weeks prior to screening
  • Chronic infectious diseases such as hepatitis, HIV etc.
  • Anaemia with a haemoglobin value 6.2 mmol/L (<10 g/dL) for women and 7.4 mmol/L (< 12 g/dL) for men at time of screening
  • Clinically significant liver or kidney function impairment, or other laboratory findings leading to the diagnosis of clinically relevant disorders (severe thyroid dysfunction etc)
  • Planned elective surgery (other than bariatric surgery) during the study period with the exception of dermatosurgical, ENT (ear, nose, throat) or dental procedures not requiring general anaesthesia and/or perioperative antibiotic treatment
  • Abuse of alcohol and/or drugs, or any other co-existing conditions that will make the subject unsuitable to participate in the study, as deemed by the investigators
  • Pregnancy or desire to become pregnant during the study period

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:基础科学
  • 分配:不适用
  • 介入模型:单组作业
  • 屏蔽:无(打开标签)

武器和干预

参与者组/臂
干预/治疗
实验性的:Obesity
Enteroscopies with biopsy retrieval and mixed meal tests with blood sampling
Enteroscopies with biopsy retrieval and mixed meal tests with blood sampling before and after Roux-en-Y gastric bypass surgery

研究衡量的是什么?

主要结果指标

结果测量
大体时间
Altered gene expression in the endocrine secretome following Roux-en-Y gastric bypass surgery
大体时间:Each participant went through six study days (two mixed meal tests and one enteroscopy procedure before and after Roux-en-Y gastric bypass surgery, respectively)
Each participant went through six study days (two mixed meal tests and one enteroscopy procedure before and after Roux-en-Y gastric bypass surgery, respectively)

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

合作者

调查人员

  • 首席研究员:Filip Knop, MD, prof.、Gentofte Hospital, University of Copenhagen

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2014年12月12日

初级完成 (实际的)

2016年12月13日

研究完成 (实际的)

2016年12月13日

研究注册日期

首次提交

2017年3月12日

首先提交符合 QC 标准的

2017年3月21日

首次发布 (实际的)

2017年3月28日

研究记录更新

最后更新发布 (实际的)

2017年3月28日

上次提交的符合 QC 标准的更新

2017年3月21日

最后验证

2017年3月1日

更多信息

与本研究相关的术语

其他研究编号

  • H-6-2014-047

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

未定

药物和器械信息、研究文件

研究美国 FDA 监管的药品

研究美国 FDA 监管的设备产品

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