Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Human Intestinal Microbiome and Surgical Outcomes in Patients Undergoing Colorectal Cancer Surgery (Microbiota)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT04005118
Recruitment Status : Recruiting
First Posted : July 2, 2019
Last Update Posted : July 2, 2019
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

Intro: Recent studies on colorectal cancer surgery have been focusing on the role of intestinal microbiome on surgical outcomes. Standard perioperative cares, like mechanic bowel preparation (MBP), administration of antibiotics (ABT) and surgery-related stress and injury influence the microbiome composition and possibly induce a shift toward a microbiome dysbiotic state, which predisposes to complicated postoperative course. Microbiome composition changes and enhanced virulence factors may increase the risk of postoperative complications, such as anastomotic leakage (AL), surgical site infection (SSI), and postoperative ileus (PI), which are known to impact on patient's overall survival and cancer recurrence.

Objective: The primary objective is to investigate if a significant association might exist between the microbiome composition and the occurrence of postoperative complications at 90 days.

Methods: 3 different microbiome samples will be taken from all patients. Two fresh fecal samples for detection of LM and fecal water preparation: a) a day before the surgery before MBP and/or ABT (LM1), b) postoperatively after first bowel movement (LM2). One sample will be taken intra-operatively from the stapled resection lines of circular stapler used for forming a colorectal anastomosis, to detect the MAM and to perform immunohistochemistry staining for detection of HACE1 expression.

DNA analysis will be performed for all samples. IHC will be performed for detecting HACE1 expression in the tumor and colorectal anastomosis tissues using anti-HACE1 antibodies. .

For proliferation assessment, human colon carcinoma cell lines HT29 will be plated in monolayers and scratched with a single scratch. Monolayers will be incubated for 24 hours with fecal water from patients with surgical complications and matched control patients without complications.

Descriptive statistics will be performed to describe the study population. This project aim to describe microbiome composition and its impact on postoperative complications.


Condition or disease
Adenocarcinoma of the Colon Adenocarcinoma of the Rectum

Layout table for study information
Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Human Intestinal Microbiome and Surgical Outcomes in Patients Undergoing Colorectal Cancer Surgery
Actual Study Start Date : May 28, 2019
Estimated Primary Completion Date : April 1, 2020
Estimated Study Completion Date : April 1, 2020

Resource links provided by the National Library of Medicine


Group/Cohort
preoperative preparation on microbiome composition
Mechanical Bowel Preparation + oral antibiotics group: receiving mechanical bowel preparation only MBP will be prepared with 4 liters of Polyethylene glycol (PEG) solution to be started 24 hours before the planned surgery. 500mg of Metronidazole will be administrated 3 times one day before the surgery at 2 pm, 3 pm and 10 pm.



Primary Outcome Measures :
  1. Rate of anastomotic leakage [ Time Frame: 90 days after surgery ]
    detected by imaging techiques (CT scan or MRI)

  2. Rate of surgical site infection [ Time Frame: 90 days after surgery ]
    1)superficial and deep infection:clinical observation of purulent discharge from the wound and/or bacterial staining from the wound 2)organ or deep space infection: imaging techniques (CT, MRI, USS)

  3. Rate of prolonged postoperative ileuss [ Time Frame: 90 days after surgery ]
    detected by clinical observation of the first bowel movement after the surgery


Secondary Outcome Measures :
  1. microbiome composition [ Time Frame: 3 months after study start date ]
    The composition of luminal microbiome and mucosal-associated microbiome will be studied by DNA analyses from fresh fecal samples and surgical anastomosis material, accordingly

  2. microbiome composition [ Time Frame: 6 months after study start date ]
    The composition of luminal microbiome and mucosal-associated microbiome will be studied by DNA analyses from fresh fecal samples and surgical anastomosis material, accordingly

  3. impact of microbiome composition on length of hospitalization [ Time Frame: at the time of patient's discharge of the hospital ]
    length of hospitalization will be detected and analyzed in association with microbiome composition

  4. Correlation between detected bacterial OTUs (Operation Taxonomic Units) and the event of reintervention [ Time Frame: 90 days after surgery ]
    In the patient group with the event of reintervention, an abundance of specific OTUs will be analysed in compare with patients with no event of reintervention.

  5. impact of microbiome metabolites on intestinal epithelial cell proliferation and wound healing [ Time Frame: 6 months after study start date ]

    Monolayers of human colon cancer cell lines HT29 will be incubated for 24 hours with fecal water from patients with surgical complications and matched control patients without complications.

    Proliferation will be calculated in two manners: 1) The time of the closure of the scratch defect will be evaluated and compared in the two group., 2)Proliferation rate will be analyzed by immunohistochemistry marker Ki 67, expression of Ki 67 will be evaluated in cells at the borders of the scratch defect


  6. Expression intensity in cytoplasm of protein ligase HACE1 in tumoral and non-tumoral tissues [ Time Frame: 6 months after study start date ]
    Immunohistochemistry with anti-HACE1 antibodies will be used to detect expression levels in tumoral (colorectal cancer) and non-tumoral (anastomotic sample) tissues. In a case of decreased expression, tissues will be analyzed by methylation PCR to detect an aberrant methylation of HACE1 and its hypermethylation

  7. Expression intensity in cytoplasm of protein ligase HACE1 in tumoral and non-tumoral tissues [ Time Frame: 3 months after study start date ]
    Immunohistochemistry with anti-HACE1 antibodies will be used to detect expression levels in tumoral (colorectal cancer) and non-tumoral (anastomotic sample) tissues. In a case of decreased expression, tissues will be analyzed by methylation PCR to detect an aberrant methylation of HACE1 and its hypermethylation


Biospecimen Retention:   Samples With DNA
3 different microbiome samples will be taken from all patients. Two fresh fecal samples for detection of luminal microbiota (LM) and fecal water preparation: a) a day before the surgery before Mechanic Bowel Preparation (MBP) and/or antibiotics (ABT) (LM1), b) postoperatively after first bowel movement (LM2). One sample will be taken intra-operatively from the stapled resection lines of circular stapler used for forming a colorectal anastomosis, to detect the Mucosal Associated Microbiota (MAM) and to perform immunohistochemistry staining for detection of HACE1 expression.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patient with rectal or left colon adenocarcinoma
Criteria

Inclusion Criteria:

  • Adult ≥ 18 years old
  • With histologically confirmed rectal or left colon adenocarcinoma by biopsy material from colonoscopy
  • Having elective colorectal surgery after standardized bowel preparation
  • Affiliated to a social security system
  • Signature of informed consent

Exclusion Criteria:

  • Major surgery 30 days before scheduled colorectal surgery
  • Administration of systemic antibiotic therapy within 30 days prior to planned colorectal surgery
  • Presenting a contraindication to elective colorectal surgery
  • Patient protected by law
  • Pregnant or breastfeeding woman

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04005118


Contacts
Layout table for location contacts
Contact: Lelde Lauka, PHD 01 49 81 41 74 ext +33 lelde.lauka@aphp.fr

Locations
Layout table for location information
France
Dr Lelde Lauka Recruiting
Créteil, France, 94000
Contact: Lauka Lelde, PhD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Layout table for investigator information
Principal Investigator: Lelde Lauka, PHD APHP

Layout table for additonal information
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT04005118     History of Changes
Other Study ID Numbers: APHP190088
First Posted: July 2, 2019    Key Record Dates
Last Update Posted: July 2, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: DATAS ARE OWN BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Intestinal microbiome
colorectal cancer
mechanical bowel preparation
postoperative complications
anastomotic leakage

Additional relevant MeSH terms:
Layout table for MeSH terms
Colorectal Neoplasms
Rectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Colonic Diseases
Intestinal Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Digestive System Diseases
Gastrointestinal Diseases
Rectal Diseases
Carcinoma