EDICT - Exercise inDuced Changes In Colorectal Cancer Tissues

Colorectal Cancer Clinical Trial

— EDICT  

Official title:

Clinical and Biological Effects of a Preoperative Exercise Programme in Colorectal Tumour and Skeletal Muscle Tissues (Exercise inDuced Changes In Colorectal Cancer Tissues)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02056691
• Other study ID #: ed-1
• Status: Completed
• Phase: N/A
• First received: February 5, 2014
• Last updated: March 9, 2018
• Start date: October 2014
• Est. completion date: October 30, 2017

Study information

• Verified date: March 2018
• Source: The Royal Bournemouth Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This pilot study looks to explore the biological effects of exercise on cancer and muscle cells using a two week exercise program (HIThigh intensity training) on 20 patients with newly diagnosed and operable colorectal cancer following diagnosis and prior to surgery. Maximal oxygen uptake will also be measured. The aim of this pilot is to assess the feasibility of recruiting participants to and carrying out a two week preoperative exercise program in patients with colorectal cancer.

Description:

Patients undergoing investigation for symptoms of colorectal cancer presenting to the hospital will undergo standard diagnostic procedures. Once resectable nonmetastatic cancer has been diagnosed (i.e. cancer that has not spread beyond the bowel), is amenable to surgical resection as decided by the colorectal multidisciplinary and if the patient fulfills the selection criteria, they will be asked if they wish to participate in the study. They will be given information regarding the study at the time of diagnosis. If they give their consent then a formal consenting process will take place at the next routine appointment.

During this appointment the patient will have the opportunity to ask questions. A member of the study team will explain the study in detail, answer any questions potential participants (and their partners/ carers) have. The patient is free to refuse participation or withdraw from the study at any time without this affecting their care, this is explained in the information and will be discussed further at the time of informed consent. If the patient agrees to participate in the trial, following the provision of informed consent and before embarking on the exercise programme they will need to fill in two questionnaires, the International Physical Activity Questionnaire (Long) and Dietary Intervention in Primary Care Questionnaire (DINE). They will be counseled to try and maintain their normal exercise level and their calorie intake. Blood samples will also be taken, analyzed and stored for further analysis including possible genetic analysis at a later stage before starting the exercise regime. They will have a muscle biopsy under local anaesthetic taken from the thigh, again for analysis and storage.

Participants will undergo an initial assessment of their baseline exercise ability and oxygen absorption using an upright exercise bike with concurrent ECG readings and breath analysis. The two week preoperative exercise regime will be planned depending on the patient's operation date. The exercise regime consists of 10 sessions of exercise against a constant load, each lasting 60s, separated by 60s of recovery eliciting 90% maximal heart rate.

The 6 sessions are held over a 2 week period. Each patients exercise ability and oxygen absorption will be remeasured at the end of the 2 week period and a second sample of blood taken for comparison. During the operation a sample of adipose tissue near the tumour site will be taken separately to the main sample. A muscle biopsy from the thigh will also be taken at the same time. As a standard of clinical care all patients are reviewed in the outpatient setting 6 weeks postoperatively. When patients attend this follow up appointment a final blood test and muscle biopsy (under local anaesthetic) will be taken to assess the longer term effects of the exercise program. Patient consent will be sought for this separately although it will be discussed at the initial introduction to the study.

Patients are free to withdraw from the study at any time and if there are any adverse events or concerns regarding the continuation of the study for a patient then they will be withdrawn.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: October 30, 2017
• Est. primary completion date: September 19, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Colorectal cancer confirmed by histology

• Considered fit for surgery by surgical and anaesthetic team

• Considered fit for physical activity programme by MDT

• Age = 18 years

• BMI = 26 kg/m2

• Not pregnant

• Non obstructing cancer

• Able to provide written informed consent

• Patients not having neoadjuvant chemotherapy

Exclusion Criteria:

• Receiving hormone therapy

• Patients with diabetes

• Patients currently on either a dietary or exercise programme reflective of the World Cancer Research Fund Guidelines.

• Cardiac or renal impairment

• Excessive use of laxatives

• History of eating disorders

• Patients with inflammatory bowel disorders/coeliac

• Strong family history/polyposis (i.e. more than one 1st degree relative <55yrs)

• Patients with previous or concurrent malignancies

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Procedure:
• Exercise programme
The exercise regime consists of 10 sessions of exercise against a constant load, each lasting 60 seconds, separated by 60 seconds of recovery eliciting 90% maximal heart rate. The 6 sessions are held over a 2 week period.
• Muscle biopsy
muscle biopsy under local anaesthetic taken from the thigh, again for analysis and storage 3 times: before, during and after the exercise programme

Locations

Country	Name	City	State
United Kingdom	The Royal Bournemouth Hospital	Bournemouth	Dorset
United Kingdom	Poole Hospital	Poole	Dorset

Sponsors (1)

Lead Sponsor	Collaborator
The Royal Bournemouth Hospital

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assess the feasibility of carrying out a two week preoperative exercise program in patients with colorectal cancer and assess the effects of preoperative exercise on the proliferation of colorectal cancer cells	To assess the feasibility of carrying out a two week preoperative exercise program in patients with colorectal cancer and to assess the effects of preoperative exercise on the proliferation of colorectal cancer cells by measuring the change in the percentage of cells staining positive for Ki67 (a measure of cell proliferation).	1 year
Secondary	Changes in molecular markers for the effects of exercise and/or diet on AMPK/ mammilian target of rapamycin signalling pathway	Measuring changes in molecular markers for the effects of exercise and/or diet on AMPK/mTOR signalling pathway (phosphorylated 4EBP1 (P4EBP1), phosphorylated protein kinase B (PPKB/AKT), and phosphorylated AMPK (PAMPK).	12 weeks
Secondary	Changes in AKT expression normal colonic tissue	Measuring changes in AKT expression normal colonic tissue - Intensity of AKT1/AKT2 staining, or AKT phosphorylation, a marker of insulin receptor signalling in cells.	12 weeks
Secondary	Assessing Apoptosis index	Assessing Apoptosis index - Percentage of tumour cells staining positive for DNA fragmentation, a marker of cells undergoing apoptosis and therefore cell death.	12 weeks
Secondary	Changes in molecular markers that may mediate or modify exercise/dietary effects in tumour tissues	Measuring changes in molecular markers that may mediate or modify exercise/dietary effects in tumour tissues (IR, IGF1R, p53 and its transcriptional target p21, ER, progesterone receptor, tumor necrosis factor-alpha converting enzyme and TIMP3).	12 weeks
Secondary	Assessing gene expression profiles	Assessing gene expression profiles focusing on gene associated with insulin resistance.	12 weeks
Secondary	Assessing the 11 gene signature	Assessing the 11 gene signature that help to predict maximal oxygen uptake gain in patients before and after exercise	12 weeks
Secondary	Blood methylation profiles.	Blood methylation profiles.	12 weeks
Secondary	Cortisol levels	Cortisol levels to evaluate levels of biological stress.	12 weeks
Secondary	Postoperative complications up to 30 days postoperatively	Postoperative complications up to 30 days postoperatively	30 days post op
Secondary	Moderator variables	Moderator variables including state of motivational readiness for exercise, weight change, depression and anxiety	12 weeks
Secondary	Irisin levels	Irisin levels before and after exercise	12 weeks