Effect of EPA on Aerobic Performance, Muscle, and Quality of Life in Colorectal Cancer Surgery Patients (EPA-colo)

Effect of EPA Nutritional Supplementation on Markers of Aerobic Performance, Lean Muscle Mass and Quality of Life on Patients Undergoing Curative Resection of Colorectal Cancer

Primary Aim is to test the Hypothesis: Nutritional supplementation with 960mg EPA three times a day positively affects muscle function and mass (assessed by muscle biopsies, assays of cellular aerobic function and DEXA scan) and inflammation (measuring cellular markers of inflammation) in patients undergoing resection of colorectal cancers.

The secondary aim is to evaluate aerobic performance assessed by cardiopulmonary exercise testing (CPEX) and perioperative outcome in patients with colorectal cancer post surgical resection.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer
• Intervention / Treatment: Other: Placebo; Dietary supplement: Experimental: Nutritional Supplementation with EPA

Detailed Description

Cancer is well documented to cause weight loss and cachexia (1). An inflammatory process driven by the presence of a tumour, can result in reduced food intake (2), increased metabolic output (3) and loss of skeletal muscle (1). They have reduced fitness and feeling of lethargy that affects activities of daily living and quality of life. The process explaining this is not well understood but thought to be due to diminished skeletal muscle mass and performance. When cancer patients undergo surgery, the trauma of surgery, entails an inflammatory process that furthermore leads to more of the above (4). Reducing this inflammatory insult would positively impact fitness, ability to respond to infections, affect length of stay in hospital, recovery from surgery and quality of life following surgery.

Eicosapentaenoic acid (EPA) is an omega-3-fatty acid, derived from fish oil and a commonly available nutritional supplement. It is believed to reduce the inflammatory effect of cancer and the trauma of surgery, in turn dampening the catabolic effect causing skeletal muscle loss. Studies on oesophageal cancer patients have previously suggested that EPA can preserve lean muscle mass (5). The investigators expect EPA to cause less lean muscle loss and improved aerobic performance. High dietary intake is not thought to have health risks (6) and EPA has recently been trialed in infant milk formulas with no adverse effects (7).

The investigators plan to recruit patients from colorectal clinic, who are due to have surgery for colorectal cancer, and give them EPA or placebo, from 5 days prior to surgery to up to 21 days following surgery. The investigators would like to measure markers of muscle function and inflammation, muscle mass, exercise performance on by cardiopulmonary exercise testing, muscle biopsy and muscle grip strength on a dynamometer.

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Derby, United Kingdom, DE22 3DT
    • Recruiting
    • School of Graduate Entry Medicine & Health, Royal Derby Hospital
    • Contact: John Williams, MD, FRCA; Phone Number: +44 1332 785566; Email: john.williams7@nhs.net
    • Principal Investigator: John Williams, MD, FRCA
    • Sub-Investigator: Tanvir Hossain, MbCHB, MRCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Colorectal cancer patients listed for open curative tumour resection by means of: Right Hemi Colectomy, Left Hemi-colectomy or Anterior Resection, not having neo-adjuvant chemotherapy.
• Aged 18 - 85 years old.

Exclusion Criteria:

• Strenuous exercise 48 hours before the preoperative assessment.
• Intramuscular injections within 48 hours of any study day.
• Known peripheral neuropathy or myopathy.
• Patients with mobility problems, wheelchair bound or have suffered a previous cerebro-vascular accident with residual impairment of mobility.
• Patients with major/ minor trauma (Motor vehicle accidents or ground falls, firearm injury, drowning, struck by and against injuries).
• Pregnant women. Pregnancy test will be done at the beginning of the study day.
• Patients without mental capacity to give signed consent.
• Patients already taking fish-oil derived nutritional supplement.
• Patients with impaired oral intake.
• Patients known to have metastatic disease.
• Patients having neoadjuvant chemotherapy prior to resection, which may confound results.
• Patients having laparoscopic procedures.
• Patients identified having cardiorespiratory comorbidity considered unsuitable for surgery: unstable angina, myocardial infarction within last 3 months, severe aortic stenosis, pulmonary hypertension, HOCM, acute myopericarditis, chronic heart failure New York Heart Association class 3 and above and impaired left ventricular ejection fraction (less than 43%). Respiratory contraindications include severe COPD, emphysema, fibrosing alveolitis, Interstitial lung disease and FEV1 less than 1.5.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Capsule form, 960 mg to be taken three times a day.
Experimental: Nutritional Supplementation with EPA; This arm will receive the nutritional supplementation of EPA 960mg Three times a day.	Dietary supplement: Experimental: Nutritional Supplementation with EPA; Capsule form, EPA, 960mg to be taken three times a day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nutritional supplementation with 960mg EPA three times a day positively affects muscle function and mass	Muscle function and mass will be assessed by muscle biopsies, assays of cellular aerobic function and DEXA scan and inflammation (measuring cellular markers of inflammation).	Baseline and 6 weeks post-op

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The secondary aim is to look at the aerobic performance.	The secondary aim is to look at the aerobic performance assessed by cardiopulmonary exercise testing (CPEX) and perioperative outcome in patients with colorectal cancer post surgical resection.	Baseline and 5 weeks post-op.

Collaborators and Investigators

• Sponsor: University of Nottingham
• Collaborators: University Hospitals of Derby and Burton NHS Foundation Trust
• Investigators: Principal Investigator: John Williams, University of Nottingham

Publications and helpful links

General Publications

• Hossain T, Phillips BE, Doleman B, Lund JN, Williams JP. A double-blind randomized controlled trial of the effects of eicosapentaenoic acid supplementation on muscle inflammation and physical function in patients undergoing colorectal cancer resection. Clin Nutr. 2020 Jul;39(7):2055-2061. doi: 10.1016/j.clnu.2019.09.009. Epub 2019 Oct 11.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Anticipated): December 1, 2012
• Study Completion (Anticipated): March 1, 2013

Study Registration Dates

• First Submitted: March 2, 2011
• First Submitted That Met QC Criteria: March 18, 2011
• First Posted (Estimate): March 22, 2011

Study Record Updates

• Last Update Posted (Estimate): December 4, 2012
• Last Update Submitted That Met QC Criteria: December 3, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 11005 (DAIDS ES Registry Number)