The Effect of Colon Cancer on Muscle Gene Expression, Body Composition, Muscle Function, and Muscle Metabolism (COMUNEX)

Rationale: Cancer cachexia is a complex metabolic syndrome characterized by clinically relevant loss of muscle mass with or without loss of fat mass. To determine how treatment methods can be most effective, full insight in changes in gene expression, body composition, muscle function and muscle metabolism are of great importance.

Objective: Main aim of the study is to investigate the differences in gene expression, body composition, muscle function and muscle metabolism in colon cancer patients compared to controls.

Study design: Observational study Study population: 40 colon cancer patients undergoing a tumor resection (30 primary tumor and 10 liver metastases) and 15 control patients undergoing an inguinal hernia repair (♂, 10) or an abdominal hysterectomy (♀, 5).

Main study parameters/endpoints: Primary study parameter will be gene expression (transcriptomic and polymerase chain reaction analyses of muscle biopsies). Secondary parameters will be body composition (determined in available CT scans and bio impedance analysis and with DEXA), muscle function parameters (grip and knee flexion/extension strength and measured in a biopsy), metabolic markers (measured in fat and muscle biopsies), biochemical markers (measured in blood/serum) and gene expression of fat biopsies.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The investigators expect no additional risk for the subjects due to the proposed measurements. Biopsies will be taken during the planned operation and therefore is not expected to cause a significant increase in burden for the patient. All other measurements are non-invasive, observational measurements with no risk of any harmful side effects.

Study Overview

• Status: Recruiting
• Conditions: Cachexia; Cancer
• Intervention / Treatment: Other: Not applicable, observational study

• Study Type: Observational
• Enrollment (Anticipated): 55

Contacts and Locations

• Study Contact: Name: Klaske van Norren, PhD; Phone Number: +31317485790; Email: klaske.vannorrren@wur.nl

Study Locations

• Netherlands
  • Gelderland
    • Ede, Gelderland, Netherlands, 6716 RP
      • Recruiting
      • Gelderse Vallei Hospital
      • Contact: Dik Snijdelaar, md; Email: snijdelaarD@zgv.nl

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

40 colon cancer (CC) patients (♀ and ♂) undergoing primary tumor resection operation (30 patients) or liver metastases surgery (10 patients) and 15 control patients undergoing an inguinal hernia repair (♂, 10) or an abdominal hysterectomy (♀, 5) will be included in the study. Since the investigators do not know the number of patients in the colon cancer group willing to cooperate in the study, the investigators decided to take 5 patients of each control group (50% men and women). Note: during the study the investigators see more men than women joining the study so therefore the investigators raised the number of male controls to 10.

Description

Inclusion Criteria:

• CC patients:

In order to be eligible to participate in this study, a subject must meet all of the following inclusion criteria:

• Diagnosed with primary colon cancer (30) or liver metastases due to colon cancer(10)

• Eligible for a primary tumor or liver metastases resection procedure

  • Controls:
• Eligible for an inguinal hernia repair (♂, 10) or an abdominal hysterectomy (♀, 5)

Exclusion Criteria:

• CC patients:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

• Having had chemotherapy or an operational procedure of the abdomen in the past 6 months

• Suffering from malabsorption

  • Controls:
• Having had treatment for previous or current tumors

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Primary colon cancer	Other: Not applicable, observational study; Not applicable, observational study
Liver metastases	Other: Not applicable, observational study; Not applicable, observational study
Inguinal hernia (control)	Other: Not applicable, observational study; Not applicable, observational study
Abdominal hysterectomy (control)	Other: Not applicable, observational study; Not applicable, observational study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle gene expression	Muscle gene expression measured by microarray in a muscle biopsy taken from the rectus abdominis	Biopsy during surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body composition	Measured using single slice staining of CT scan made for diagnostic purposes.	Before surgery
Muscle function	Measured using hand-grip strength	Before surgery
Muscle protein metabolism	Measured in a muscle biopsy taken from the rectus abdominis	Biopsy during surgery
Adipose tissue gene expression	Adipose tissue gene expression measured using PCR or micro-array in abdominal and subcutaneous fat	Biopsy during surgery
Cytokine parameters in the blood	Blood plasma cytokine levels measured using multiplex or similar technique	Blood taken prior to surgery
Micro-nutrient parameters in the blood	Micro-nutrient levels in the blood measured using LCMS, ELISA or similar techniques	Blood taken prior to surgery
Cholesterol levels in the blood	Cholesterol levels in the blood measured by GCMS	Blood taken prior to surgery

Collaborators and Investigators

• Sponsor: Wageningen University
• Collaborators: Top Institute Food and Nutrition; Gelderse Vallei Hospital
• Investigators: Principal Investigator: Klaske van Norren, PhD, Wageningen University and Research

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2017
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: December 7, 2018
• First Submitted That Met QC Criteria: December 21, 2018
• First Posted (Actual): December 28, 2018

Study Record Updates

• Last Update Posted (Actual): June 29, 2021
• Last Update Submitted That Met QC Criteria: June 28, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Body Weight; Body Weight Changes; Emaciation; Weight Loss; Cachexia
• Other Study ID Numbers: NL58188.081.16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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