PeRioperative Omega Three and the Effect on ImmuNity (PROTEIN)

A Randomized Controlled Trial of Standard or DHA/EPA Supplemented Enteral Nutrition in Patients Undergoing Laparoscopic Colorectal Surgery

Bowel cancer is the second most common cause of cancer-related death in the UK, with 50,000 new cases and over 15,000 deaths annually. Surgery is the mainstay of treatment and the most common complications are an infection of the wound or lungs. These can lengthen hospital stay, reduce the quality of life, and even increase the risk of death. Bowel cancer patients are often malnourished. Optimising nutrition with supplements such as fish-oils can improve the immune response of patients, helping prevent such complications, shorten hospital stay, improve quality of life and overall survival.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Sarcopenia; Surgery; Surgery--Complications; Surgical Site Infection; Nutritional Deficiency; Complication, Postoperative; Infected Wound; Phagocytic Dysfunction
• Intervention / Treatment: Dietary supplement: Omega-3

Detailed Description

Bowel cancer is the second most common cause of cancer-related death in the UK, with 50,000 new cases and over 15,000 deaths annually. Surgery is the mainstay of treatment and the most common complications are an infection of the wound or lungs. These can lengthen hospital stay, reduce the quality of life, and even increase the risk of death. Bowel cancer patients are often malnourished. Optimising nutrition with supplements such as fish-oils can improve the immune response of patients, helping prevent such complications, shorten hospital stay, improve quality of life and overall survival. We are increasingly familiar with the term BMI, body mass index, which we use to categorise obesity in healthcare. A newer term in this realm is that of sarcopenia, a low muscle mass relative to your size, unrelated to your weight or fat density. This can be measured in a number of ways, including on a scan performed routinely in bowel cancer care, a CT scan. Evidence shows that people with low muscle mass, irrespective of their overall weight, experience more complications than those who have healthier amounts of muscle. We hypothesise that patients supplemented with fish oils both before and after surgery will experience an enhancement of their immune response, and subsequently encounter fewer infectious complications, a shorter length of hospital stay and improved quality of life. We also predict fewer patients having extra nutrition before and after surgery will develop sarcopenia and avoid the risks associated with that condition. The trial will only take place in those with bowel cancer who are planned to have a keyhole operation, as this is now the most commonplace approach to surgery. We plan to recruit 40 patients, 20 to receive the supplement, and 20 to form a comparison or control group.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Surrey
    • Guildford, Surrey, United Kingdom, GU2 7WG
      • Royal Surrey County Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with colorectal cancer undergoing elective laparoscopic colorectal resection.
• Adult aged 18 or over.
• Capacity to consent

Exclusion Criteria:

• Pre-existing diagnosis of Diabetes mellitus, requiring medication.
• Consumption of > 3 alcoholic drinks/day
• Already on omega-3 supplementation
• Pregnant
• Patients on heparin infusion perioperatively
• Patients on immunosuppressive drugs
• Regular / Daily smokers
• Patients requiring a blood transfusion at any point day 7 pre-op to day 1 post operatively.
• Vegan or Vegetarian
• Allergy to cows milk or wheat

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Patients undergoing standard laparoscopic colorectal resection with no omega-3 enriched peri-operative nutritional support
Experimental: Omega-3; Patients in this group will receive 7 days pre and 7 days post surgery of a nutritional supplement enriched with 1.42g/dose of the fish oils EPA and DHA. The supplement is pre-mixed and will be taken twice daily for a total of 14 days.	Dietary supplement: Omega-3; 200ml, pre-mixed oral nutritional supplement supplying 1.42g per bottle of EPA and DHA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Phagocytosis of pathogens	Phagocytosis of E.Coli, S.Aureus and Candida measured with flow cytometry	Baseline [2-4 weeks before surgery], Day of Surgery [day 7 post nutritional supplementation], Day 1 post surgery [day 8 post supplementation].
Changes in cell membrane composition	Using gas chromatography, measuring the percentage of omega-3 within cell membranes	Baseline [2-4 weeks before surgery], Day of Surgery [day 7 post nutritional supplementation], Day 1 post surgery [day 8 post supplementation].

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infectious complications	Descriptions laid out in supplement 1 for diagnostic criteria	30 days
Non-infectious complications	Descriptions laid out in supplement 1 for diagnostic criteria	30 days
Length of hospital stay	Length of stay in days as per electronic discharge records	A maximum of 90 days
Sarcopenia	Changes in body composition measured on CT scan	Baseline [Pre-operative staging CT scan] and 6 month +/-2 months
Quality of Life (EORTC: QLQC30)	Quality of life questionnaire EORTC: QLQC30. A 30 element validated questionnaire. Symptoms are grouped into scales: Physical Function, Role Function, Emotional Function, Cognitive Function, and Social Function. In addition symptom scales including: Fatigue, Nausea, vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhoea, and financial difficulties. 28 of the scales range from 1 to 4, 4 being most symptomatic, 1 least so. The 2 remaining scales for overall health and quality of life are scaled 1-7, with 7 being the best and 1 the worst. The 30 questions can be combined for a global score, in which instance the 2 global scales are reversed so that 7 becomes the worst quality of life or health and 1 the best.	Baseline and 3 weeks post surgery +/- 7 days
Changes in Hand grip strength	Physical measurement of hand grip strength using hand dyanamometer to assist in diagnosis of sarcopenia / functional status.	Baseline [Pre-operative staging CT scan] and 6 month +/-2 months

Collaborators and Investigators

• Sponsor: Royal Surrey County Hospital NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2018
• Primary Completion (Actual): September 19, 2019
• Study Completion (Actual): September 19, 2019

Study Registration Dates

• First Submitted: July 3, 2018
• First Submitted That Met QC Criteria: July 24, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Actual): September 28, 2022
• Last Update Submitted That Met QC Criteria: September 26, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: omega 3 fatty acids; enhanced recovery; macrophages; perioperative nutrition
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Neurologic Manifestations; Hematologic Diseases; Nutrition Disorders; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Leukocyte Disorders; Muscular Atrophy; Atrophy; Wound Infection; Sarcopenia; Malnutrition; Postoperative Complications; Surgical Wound Infection; Phagocyte Bactericidal Dysfunction
• Other Study ID Numbers: 18SURN238410

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Ethical approval allows for sharing of anonymised data with collaborators at the University of Surrey.

Drug and device information, study documents

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