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出境医 / 临床实验 / Post-operative Ileus and Gut Microbiota

Post-operative Ileus and Gut Microbiota

Study Description
Brief Summary:
Postoperative ileus (POI) is a common clinical condition after abdominal surgical procedure, leading to increased patient morbidity and prolonged hospitalisation.The mechanism of POI is not very clear until now. At the end of the 20th century, the inflammatory-mediated ileus hypothesis was introduced. But the initial trigger of the inflammatory cascade is unclear.Previous study demonstrate a clear association between colonic transit time, gut microbiota composition and urinary metabolic phenotype. Here the investigators suggest that the perioperative gut microbiota may contribute to POI.

Condition or disease Intervention/treatment
Post-operative Ileus Other: Fecal and blood samples collection for analysis

Detailed Description:

Postoperative ileus (POI) is a common clinical condition after abdominal surgical procedure, leading to increased patient morbidity and prolonged hospitalisation.

The clinical manifestations include abdominal distension, nausea, vomiting and the inability to pass stools or tolerate a solid diet. In addition to the discomfort experienced by patients, postoperative ileus is also an important risk factor for complications such as wound dehiscence and pulmonary and thromboembolic complications. Ileus was found to be an important predictor of extended postoperative hospital stays and costs in patients undergoing colectomy.

The mechanism of POI is not very clear until now. At the end of the 20th century, the inflammatory-mediated ileus hypothesis was introduced. But the initial trigger of the inflammatory cascade is unclear The innate immune system recognises two large classes of macromolecules: first, those related to pathogens or pathogen-associated molecular patterns (PAMPs), and secondly, molecules released in response to cell damage or damage-associated molecular patterns (DAMPs). The prototype of PAMPs is lipopolysaccharide (LPS), a constituent of the Gram-negative bacterial cell wall. Translocation of microbial products into the intestinal tissue is a well-documented feature in POI. Previous study demonstrate a clear association between colonic transit time, gut microbiota composition and urinary metabolic phenotype. Here the investigators suggest that the perioperative microbiome may contribute to POI. This study apply NGS(next generation sequencing) technique to analyse the composition of the perioperative gut microbiota of CRC(colorectal cancer) patients, then analysis the relationship between the dynamic variation of gut microbiota and POI.

Study Design
Layout table for study information
Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Case-Control
Time Perspective: Retrospective
Official Title: Post-operative Ileus of Colorectal Cancer Patients Associated With Perioperative Gut Microbiota
Actual Study Start Date : April 1, 2019
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : December 31, 2020
Arms and Interventions
Group/Cohort Intervention/treatment
Delayed transit
CRC patients with delayed gut transit recovery( first time defecation >3 day )
Other: Fecal and blood samples collection for analysis
Fecal sample analysis will consist of the following procedure : Microbial DNA extraction, amplicon library construction, sequencing and analysis; Clustering "MiSeq" reads into operational taxonomic units (OTUs).

Normal transit
CRC patients with normal gut transit recovery( first time defecation <=3 day )
Other: Fecal and blood samples collection for analysis
Fecal sample analysis will consist of the following procedure : Microbial DNA extraction, amplicon library construction, sequencing and analysis; Clustering "MiSeq" reads into operational taxonomic units (OTUs).

Outcome Measures
Primary Outcome Measures :
  1. Change in gut microbiome dynamics in colorectal cancer patients during the perioperative period between two groups [ Time Frame: The day before operation day, the first to the 10th day after operation (everyday the patient's faeces will be collected for microbiome analysis, if the patient has no faeces,we will skip that day to next day for fecal collection) ]
    The diversity, structure of fecal microbiota and relative abundance of special bacterial taxa 16S rRNA gene sequencing will be performed.

  2. The time ranging from operation day to the day of first defecation [ Time Frame: Up to 10 days ]
    The recovery of gut transit can be indicated by the first defecation


Secondary Outcome Measures :
  1. Concentration of plasma i-FABP(intestinal fatty acid-binding protein) [ Time Frame: The day before operation day, every day from first to fifth post-operative day ]
    The detection of i-FABP is useful to determine localized changes in intestinal damage.

  2. Concentration of plasma LPS [ Time Frame: The day before operation day, every day from first to fifth post-operative day ]
    The presence of lipopolysaccharide (LPS) has been used as an indirect measurement of bacterial translocation and systemic exposure to bacteria.

  3. Concentration of fecal LPS [ Time Frame: The day before operation day, the first to the 10th day after operation (everyday the patient's faeces will be collected for microbiome analysis, if the patient has no faeces,we will skip that day to next day for fecal collection) ]
    LPS was derived from gram-negative bacteria in the intestinal tract, and LPS in blood was derived from feces.

  4. Concentration of fecal calprotectin [ Time Frame: The day before operation day, the first to the 10th day after operation (everyday the patient's faeces will be collected for microbiome analysis, if the patient has no faeces,we will skip that day to next day for fecal collection) ]
    Fecal calprotectin is not only an indicator of intestinal inflammation, but also an indicator of intestinal mucosal barrier.


Biospecimen Retention:   Samples With DNA
Fecal sample analysis will consist of the following procedure : Microbial DNA extraction, amplicon library construction, sequencing and analysis; Clustering "MiSeq" reads into operational taxonomic units (OTUs).

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   35 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Study participants are patients need undergo an exhaustive colorectal cancer surgical resection in the First Affiliated Hospital of Harbin Medical University from May 1, 2018 to Dec 31, 2019.
Criteria

Inclusion Criteria:

  • Requirements of informed consent and assent of participant, parent or legal guardian as applicable
  • Patients with colorectal cancer scheduled for radical coloproctectomy and between the age of 35 and 80 years old without considering sex.
  • Patients with BMI= 18.5-23.9

Exclusion Criteria:

  • Patients with colorectal cancer with distant metastasis
  • Chronic renal diseases and hepatic cirrhosis
  • Chronic ischemic heart disease with unstable angina, chronic heart failure at class III or IV and acute myocardial infarction in the last 6 months
  • Individuals with a history of Chronic diarrhea
  • Individuals with a history of Diabetes mellitus
  • Individuals with a history of Hypertension
  • Individuals with a history of autoimmune diseases
  • Use of antibiotics and probiotics 3 mouth before samples collection
  • Individuals with a history of abdominal operation due to any reason
  • Individuals with any history of cancer other than colorectal cancer
  • Individuals with Inflammatory bowel disease
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Yunwei Wei, professor +86045185553099 hydwyw11@hotmail.com
Contact: Yang Liu, assistant research fellow +8618345180169 lyang712@icloud.com

Locations
Layout table for location information
China, Heilongjiang
First affiliated hospital of Harbin medical university Recruiting
Harbin, Heilongjiang, China, 150001
Contact: Yunwei Wei    +86-0451-85553099    hydwyw11@hotmail.com   
Sponsors and Collaborators
First Affiliated Hospital of Harbin Medical University
Investigators
Layout table for investigator information
Study Director: Yunwei Wei First Affiliated Hospital of Harbin Medical University
Tracking Information
First Submitted Date May 13, 2019
First Posted Date July 8, 2019
Last Update Posted Date July 8, 2019
Actual Study Start Date April 1, 2019
Estimated Primary Completion Date September 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 4, 2019)
  • Change in gut microbiome dynamics in colorectal cancer patients during the perioperative period between two groups [ Time Frame: The day before operation day, the first to the 10th day after operation (everyday the patient's faeces will be collected for microbiome analysis, if the patient has no faeces,we will skip that day to next day for fecal collection) ]
    The diversity, structure of fecal microbiota and relative abundance of special bacterial taxa 16S rRNA gene sequencing will be performed.
  • The time ranging from operation day to the day of first defecation [ Time Frame: Up to 10 days ]
    The recovery of gut transit can be indicated by the first defecation
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: July 4, 2019)
  • Concentration of plasma i-FABP(intestinal fatty acid-binding protein) [ Time Frame: The day before operation day, every day from first to fifth post-operative day ]
    The detection of i-FABP is useful to determine localized changes in intestinal damage.
  • Concentration of plasma LPS [ Time Frame: The day before operation day, every day from first to fifth post-operative day ]
    The presence of lipopolysaccharide (LPS) has been used as an indirect measurement of bacterial translocation and systemic exposure to bacteria.
  • Concentration of fecal LPS [ Time Frame: The day before operation day, the first to the 10th day after operation (everyday the patient's faeces will be collected for microbiome analysis, if the patient has no faeces,we will skip that day to next day for fecal collection) ]
    LPS was derived from gram-negative bacteria in the intestinal tract, and LPS in blood was derived from feces.
  • Concentration of fecal calprotectin [ Time Frame: The day before operation day, the first to the 10th day after operation (everyday the patient's faeces will be collected for microbiome analysis, if the patient has no faeces,we will skip that day to next day for fecal collection) ]
    Fecal calprotectin is not only an indicator of intestinal inflammation, but also an indicator of intestinal mucosal barrier.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Post-operative Ileus and Gut Microbiota
Official Title Post-operative Ileus of Colorectal Cancer Patients Associated With Perioperative Gut Microbiota
Brief Summary Postoperative ileus (POI) is a common clinical condition after abdominal surgical procedure, leading to increased patient morbidity and prolonged hospitalisation.The mechanism of POI is not very clear until now. At the end of the 20th century, the inflammatory-mediated ileus hypothesis was introduced. But the initial trigger of the inflammatory cascade is unclear.Previous study demonstrate a clear association between colonic transit time, gut microbiota composition and urinary metabolic phenotype. Here the investigators suggest that the perioperative gut microbiota may contribute to POI.
Detailed Description

Postoperative ileus (POI) is a common clinical condition after abdominal surgical procedure, leading to increased patient morbidity and prolonged hospitalisation.

The clinical manifestations include abdominal distension, nausea, vomiting and the inability to pass stools or tolerate a solid diet. In addition to the discomfort experienced by patients, postoperative ileus is also an important risk factor for complications such as wound dehiscence and pulmonary and thromboembolic complications. Ileus was found to be an important predictor of extended postoperative hospital stays and costs in patients undergoing colectomy.

The mechanism of POI is not very clear until now. At the end of the 20th century, the inflammatory-mediated ileus hypothesis was introduced. But the initial trigger of the inflammatory cascade is unclear The innate immune system recognises two large classes of macromolecules: first, those related to pathogens or pathogen-associated molecular patterns (PAMPs), and secondly, molecules released in response to cell damage or damage-associated molecular patterns (DAMPs). The prototype of PAMPs is lipopolysaccharide (LPS), a constituent of the Gram-negative bacterial cell wall. Translocation of microbial products into the intestinal tissue is a well-documented feature in POI. Previous study demonstrate a clear association between colonic transit time, gut microbiota composition and urinary metabolic phenotype. Here the investigators suggest that the perioperative microbiome may contribute to POI. This study apply NGS(next generation sequencing) technique to analyse the composition of the perioperative gut microbiota of CRC(colorectal cancer) patients, then analysis the relationship between the dynamic variation of gut microbiota and POI.

Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Retrospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Fecal sample analysis will consist of the following procedure : Microbial DNA extraction, amplicon library construction, sequencing and analysis; Clustering "MiSeq" reads into operational taxonomic units (OTUs).
Sampling Method Non-Probability Sample
Study Population Study participants are patients need undergo an exhaustive colorectal cancer surgical resection in the First Affiliated Hospital of Harbin Medical University from May 1, 2018 to Dec 31, 2019.
Condition Post-operative Ileus
Intervention Other: Fecal and blood samples collection for analysis
Fecal sample analysis will consist of the following procedure : Microbial DNA extraction, amplicon library construction, sequencing and analysis; Clustering "MiSeq" reads into operational taxonomic units (OTUs).
Study Groups/Cohorts
  • Delayed transit
    CRC patients with delayed gut transit recovery( first time defecation >3 day )
    Intervention: Other: Fecal and blood samples collection for analysis
  • Normal transit
    CRC patients with normal gut transit recovery( first time defecation <=3 day )
    Intervention: Other: Fecal and blood samples collection for analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Unknown status
Estimated Enrollment
 (submitted: July 4, 2019)
40
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 31, 2020
Estimated Primary Completion Date September 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Requirements of informed consent and assent of participant, parent or legal guardian as applicable
  • Patients with colorectal cancer scheduled for radical coloproctectomy and between the age of 35 and 80 years old without considering sex.
  • Patients with BMI= 18.5-23.9

Exclusion Criteria:

  • Patients with colorectal cancer with distant metastasis
  • Chronic renal diseases and hepatic cirrhosis
  • Chronic ischemic heart disease with unstable angina, chronic heart failure at class III or IV and acute myocardial infarction in the last 6 months
  • Individuals with a history of Chronic diarrhea
  • Individuals with a history of Diabetes mellitus
  • Individuals with a history of Hypertension
  • Individuals with a history of autoimmune diseases
  • Use of antibiotics and probiotics 3 mouth before samples collection
  • Individuals with a history of abdominal operation due to any reason
  • Individuals with any history of cancer other than colorectal cancer
  • Individuals with Inflammatory bowel disease
Sex/Gender
Sexes Eligible for Study: All
Ages 35 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries China
Removed Location Countries  
 
Administrative Information
NCT Number NCT04009954
Other Study ID Numbers Yunwei Wei 2019-04-19
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party First Affiliated Hospital of Harbin Medical University
Study Sponsor First Affiliated Hospital of Harbin Medical University
Collaborators Not Provided
Investigators
Study Director: Yunwei Wei First Affiliated Hospital of Harbin Medical University
PRS Account First Affiliated Hospital of Harbin Medical University
Verification Date April 2019

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