Impact of Exercise and Hyperlipidic Meal on Free Circulating DNA in Patients With Metastatic Colonic Cancer and Healthy Subjects (ASRHACOLS)

Impact of Sport Practice and Hyperlipidic Meal on Free Circulating DNA in Patients With Metastatic Colonic Cancer and Healthy Subjects. Physiological Pilot Study

The study of circulating tumoral DNA makes it possible to study, without invasive procedures or pathological studies, the tumoral DNA circulating in the blood of a patient and its various alterations. In patients with colon-rectal cancer with resected tumor, circulating tumor DNA can be used as a predictive biomarker of metastatic relapse of cancer. However, the routine extension of circulating tumoral DNA remains limited due to several difficulties. One of the pifalls that circulating tumor DNA is greatly diluted by healthy circulating DNA from non-tumor cells. The amount of healthy circulating DNA has been described as being influenced by certain physiological parameters. The aim of the study is to increase knowledge on the influence of physiological factors associated with sports activity and meal on the release kinetics of circulating DNA.

Study Overview

• Status: Not yet recruiting
• Conditions: Colon Cancer
• Intervention / Treatment: Other: Moderate intensity physical effort; Other: Hyperlipidic meal; Diagnostic test: Measure of circulating DNA; Other: Low intensity physical effort

Detailed Description

20 subjects free of malignancy (Male-Female Ratio 2 to 1) the variation in the concentration of DNA circulating between the value measured on an empty stomach after 1 hour of rest, then at the end of each of the successive stages of moderate intensity physical effort: pedaling 15 minutes at 75 Watt then 100 Watt of the ergometer. Dosages will be repeated after 15, 30 and 60 minutes of recovery. After an hour of recovery, the subject will be asked to consume a meal rich in fat. The circulating DNA will be measured 2 hours after the end of the meal.

40 patients with colon cancer will be enrolled for a two visit study. The first visit will be planned at the first cycle of chemotherapy, before the chemotherapy. At this visit, the influence of exercise on plasma concentrations of circulating free DNA will also be studied in 40 patients with colon cancer. Free circulating DNA will be measured on an empty stomach after 1 hour of rest, then immediately after low-intensity physical effort : pedaling 3 minutes at the 30 Watt level of the ergometer) and after 15, 30 and 60 minutes of recovery. After an hour of recovery, the subject will be proposed to consume a meal rich in fat. The circulating DNA will be measured 2 hours after the end of the meal. The second visit will be planned at the first second of chemotherapy, before the chemotherapy. Free circulating DNA will be measured on an empty stomach after 1 hour of rest, then immediately after low-intensity physical effort : pedaling 3 min at the 30 Watt level of the ergometer, and after 15, 30 and 60 minutes of recovery.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Annie BERGERA; Phone Number: 33 1 44 84 17 24; Email: gestion-locale.drc@aphp.fr

Study Locations

• France
  • Île-de-France
    • Paris, Île-de-France, France, 75015
      • Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou
      • Contact: Pierre LAURENT-PUIG, MD-PHD; Phone Number: 331 76 53 43 81; Email: pierre.laurent-puig@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Subjects free of malignancy

   • men or women 40-70 yrs aged

2. Patients with colon cancer

   • men or women 18-85 yrs aged
   • Biopsy-proven colon cancer with indication to chemiotherapy
   • Chemiotherapy (first line or second line) not started

Exclusion Criteria:

1. All subjects

   • Ischemic cardiac history
   • known heart disease
   • blood hemoglobin concentration <8g / dl
   • Acute or chronic systemic illnesses, (apart from diabetes, essential or secondary hypertension for patients)
   • Pregnancy or breastfeeding or in progress

2. Subjects free of malignancy

   • Cardiovascular risk factor (active smoking or greater than 10 pack-years, diabetes, hypertension or known dyslipidemia not controlled by the diet)
   • Glomerular filtration rate estimated by the CKD epi (Chronic Kidney Disease - Epidemiology Collaboration) formula < 60 ml.min-1.1.73 m-²
   • Contraindication to exercise
   • Drug taking in progress (except estrogen-progestogen contraception)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subjects free of malignancy; Moderate intensity physical effort and meal (once)	Other: Moderate intensity physical effort; Pedaling 15 minutes at 75 Watt then 100 Watt of the ergometer; Other: Hyperlipidic meal; Eating an hyperlipidic meal 60 minutes after a physical effort; Diagnostic test: Measure of circulating DNA; Multiple measure of circulating DNA: on an empty stomach, at the end of the physical effort, after 15, 30 and 60 minutes of rest, 120 minutes after an hyperlipidic meal. An additional measure will occur for subjects free of malignancy during the effort.
Experimental: Patients with colon cancer; Low intensity physical effort and meal (visit 1, day of cycle 1 chemotherapy) and low intensity physical effort (visit 2, day of cycle 2 chemotherapy)	Other: Hyperlipidic meal; Eating an hyperlipidic meal 60 minutes after a physical effort; Diagnostic test: Measure of circulating DNA; Multiple measure of circulating DNA: on an empty stomach, at the end of the physical effort, after 15, 30 and 60 minutes of rest, 120 minutes after an hyperlipidic meal. An additional measure will occur for subjects free of malignancy during the effort.; Other: Low intensity physical effort; Pedaling 3 minutes at the 30 Watt level of the ergometer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in circulating DNA induced by moderate effort in subjects free of malignacy	Variation in the concentration of circulating DNA between the value measured after 1 hour of rest, during and at recovery of moderate intensity physical effort	0, 3, 15 minutes of exercise, 15, 30 and 60 minutes of recovery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in circulating DNA induced by hyperlipidic meal in subjects free of malignacy	Variation in the concentration of circulating DNA between the value measured before and after an hyperlipidic meal in subjects free of malignancy	0 minutes (before eating) and 120 minutes after eating
Change in circulating DNA induced by moderate effort in patients with colon cancer	Variation in the concentration of circulating DNA between the value measured after 1 hour of rest, during and at recovery of low intensity physical effort	0, 15, 30 and 60 minutes of recovery.
Change in circulating DNA induced by hyperlipidic meal in patients with colon cancer	Variation in the concentration of circulating DNA between the value measured before and after an hyperlipidic meal	0 minutes (before eating) and 120 minutes after eating

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Eurofins Biomnis
• Investigators: Principal Investigator: Pierre LAURENT-PUIG, MD-PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2023
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): June 1, 2024

Study Registration Dates

• First Submitted: November 15, 2021
• First Submitted That Met QC Criteria: December 6, 2021
• First Posted (Actual): December 7, 2021

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 14, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Exercise; colon cancer; Meal; circulating DNA
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms
• Other Study ID Numbers: APHP201461 (Other Identifier: AP-HP); IDRCB 2020-A02872-37 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared
• IPD Sharing Time Frame: Two years after the last publication

IPD Sharing Access Criteria

Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared Supporting Information: Study Protocol Informed Consent Form (ICF)

Time Frame:

Two years after the last publication

Access Criteria:

Data sharing must be accepted by the sponsor and the PI based on a scientific project and scientific involvement of the PI team. Collaboration will be fostered.

Data sharing must respect the agreements made with funders.

Teams wishing obtain IPD must meet the sponsor and IP team to present scientific (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contractual agreement.

Processing of shared data must comply with European General Data Protection Regulation (GDPR).

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

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