Colorectal Omics and ofCS Proteoglycans (COCO)

Colorectal OmiCs and Oncofetal Chondroitin Sulfate-modified Proteoglycans

This observational study aims to test proteomics, metabolomics and proteoglycans as predictors of postoperative complications after colorectal surgery and as biomarkers of colorectal cancer.

The main questions to answer are:

• can these biomarkers predict anastomotic leakages
• can these biomarkers predict recurrence after colorectal cancer
• can these biomarkers be used as diagnostic tests for colorectal cancer
• can these biomarkers be identified in the tumor

Participants will undergo elective colorectal resection or stoma closure.

Study Overview

• Status: Not yet recruiting
• Conditions: Inflammatory Bowel Diseases; Colorectal Cancer; Diverticulitis, Colonic; Stoma Colostomy
• Intervention / Treatment: Procedure: Colorectal resection or stoma closure

Detailed Description

The prospective cohort study will include 1,000 patients undergoing elective colorectal resections or colostomy reversal at two colorectal centers in Denmark. Repeating study blood samples will be collected on each postoperative day (POD) 1-4 or until discharge. If the participants are diagnosed with cancer, blood sampling is planned 26-35 days after the index procedure, and after one, two, and three years, a tumor biopsy will be taken from the fresh specimen in the operation theatre.

Analyses of blood plasma and tissue for oncofetal chondroitin sulfate (ofCS) proteoglycans, proteomics, and metabolomics will be performed on those repeating blood samplings to:

• To investigate whether metabolomics, proteomics, and ofCS techniques can identify new biomarkers where charges in plasma levels can predict or detect subclinical AL (primary outcome) and other major postoperative complications after colorectal surgery and prediction of 90-day and three-year mortality.
• To investigate whether the APOE genotype is associated with the risk of AL and other major postoperative complications and long-term outcomes, i.e., recurrence and mortality, after colorectal surgery.
• To examine whether metabolomics and proteomics can identify new biomarkers predicting recurrence after colorectal cancer resections.
• To identify other potential biomarkers that might enable early cancer diagnosis.
• Whether proteoglycans can be used as a diagnostic test with a high degree of separability to identify tumor markers that are usable in a clinical setting (primary outcome). Participants with colorectal cancer will be compared with a control group of participants with benign conditions.
• Whether the level of proteoglycans measured correlates to the tumor load.
• Whether the proteoglycans and proteomics detected in plasma are presented in tumor tissue from the resected specimen.
• Whether the proteoglycans detected can be used as tumor markers with a high degree or measure of separability for monitoring recurrence after colorectal cancer in a clinical setting (primary outcome).

Postoperative and follow-up data will be collected prospectively for the electronic health records.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Nanna B Hupfeld, ph.d.; Phone Number: +4548292793; Email: nanna.baekvang.hupfeld.01@regionh.dk

Study Locations

• Denmark
  • Hillerød, Denmark, 3400
    • Nordsjaellands Hospital
    • Contact: Nanna B Hupfeld, MD; Phone Number: +4548292793; Email: nanna.baekvang.hupfeld.01@regionh.dk
    • Contact: Claus A Bertelsen, PhD; Phone Number: +4548295972; Email: claus.anders.bertelsen@regionh.dk
  • Viborg, Denmark, 8800
    • Regionshospitalet Viborg
    • Contact: Uffe S Løwe, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients planned for elective colorectal surgery

Description

Inclusion Criteria:

• Patients diagnosed or with suspicion of colorectal cancer or adenoma, inflammatory bowel disease, late complications to colon diverticulosis, colostomy reversal or other diagnoses requiring colorectal resection.
• Patients planned to undergo elective surgical procedures coded as KJFB20-KJFB99, KJFG30-37 or KJGB00-97 according to the Danish modification of the NOMESCO Classification of Surgical Procedures
• Able to speak Danish, English, or other languages where professional interpretation is available
• Able to give informed consent

Exclusion Criteria:

• Patients undergoing synchronous: liver resection (patients undergoing metastasectomies can be included); total gastrectomy or cardia resection; Whipple's procedure or another major pancreatic resection (resections of the pancreatic tail can be included); total or partial nephrectomies or cystectomy
• Patients previously included in the study
• Patients known to be pregnant (pregnancy test not required)
• Non-resident in Denmark

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study cohort; Patients undergoing elective colorectal resection or stoma closure	Procedure: Colorectal resection or stoma closure; Elective open or minimally invasive resection for colorectal cancer, IBD or other benign colorectal disorder, or stoma closure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of anastomotic leakage diagnosed by CT-scan or reoperation	Anastomotic leakage after colorectal resection with anastomosis or stoma closure	30 days
Rate of major postoperative complications	Major postoperative complication (Clavien-Dindo score 3B or higher, and DVT and pulmonary embolism) after colorectal resection with anastomosis or stoma closure	30 days
Short-term mortality	Postoperative mortality after colorectal resection with anastomosis or stoma closure	90 days
Recurrence after colorectal cancer	Recurrence after radical resection, diagnosed by imaging modalities or tissue biopsy	4 years
Diagnostic value of omics and other biomarkers detecting colorectal cancer	Identifying omics and chondroitin sulfate-modified proteoglycans that can be used i a clinical setting to identify colorectal cancer patients	30 days
Correlation between biomarker in plasma and tissue	Does presence of tumor markers in blood plasma correlate with the same tumor makers in the tumor tissue	30 days

Collaborators and Investigators

• Sponsor: Claus Anders Bertelsen, PhD, MD
• Collaborators: Viborg Regional Hospital
• Investigators: Study Chair: Claus A Bertelsen, PhD, Department of Surgery, Copenhagen University Hospital - North Zealand

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2032

Study Registration Dates

• First Submitted: February 22, 2024
• First Submitted That Met QC Criteria: February 29, 2024
• First Posted (Estimated): March 1, 2024

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Diverticular Diseases; Diverticulosis, Colonic; Inflammatory Bowel Diseases; Diverticulitis; Diverticulitis, Colonic
• Other Study ID Numbers: COCO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Results will be published by the investigators in academic journals. Sharing of generated study data will be carried out in several different ways. After acceptance from the participant and the ethics committee of the Capital Region of Denmark, individual participant data and blood plasma will be available to potential collaborators interested in colorectal disorders.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No