Perioperative Immunonutrition in Colorectal Cancer Patients Undergoing Abdominal Surgery (PERIOP-02)

A Translational Clinical Trial of Perioperative Immunonutrition in Colorectal Cancer Patients Undergoing Abdominal Surgery: PERIOP-02

The immune system plays an important role in helping to kill and prevent cancers. Cells of the immune system, such as natural killer (NK) cells and T cells, do not work as well following surgery. Arginine, an amino acid, is fundamental in metabolic processes of the body. Surgery has shown to cause a reduction of arginine in the body. In turn, this deficiency causes NK cell suppression. In this study, we want to look at the effects of arginine supplementation before and after surgery on NK cell function in surgery patients. In this study, we will be using a nutritional supplement containing arginine and a placebo drink (provided by Enhanced Medical Nutrition) that will be taken by colorectal cancer patients 5 days before surgery and 5 days after surgery. Using patient blood samples, we will measure NK cell levels, arginine levels and also arginase activity.

Study Overview

• Status: Completed
• Conditions: ColoRectal Cancer
• Intervention / Treatment: Dietary supplement: Immunonutrition with arginine; Dietary supplement: Immunonutrition without Arginine

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with a diagnosis of a primary colorectal cancer and eligible for surgical resection.
• Patients > 18 years of age
• Eligible patients must have signed a consent for surgical resection of the malignancy.
• Ability to understand and provide a signed informed consent form (ICF) approved by the Research ethics board (REB).
• Adequate kidney function with Creatine clearance>30mL/min
• Hemoglobin level >90 mg/dL
• Ability to comply with protocol requirements.

Exclusion Criteria:

• Prior adjuvant chemotherapy or radiation within 8 weeks of planned surgery.
• Documented significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication (e.g. systemic corticosteroids, azathioprine, cyclosporin A). Subjects may be on physiologic doses of replacement prednisone or equivalent doses of corticosteroid (<7.5 mg daily).
• Subjects with resting hypotension (Blood pressure <90/50 at rest).
• History of autoimmune disease, such as but not restricted to, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis.
• Serious intercurrent chronic or acute illness, or other illness considered by the investigator as an unwarranted high risk for an investigational product.
• Active infection of any site and/or active herpes requiring ongoing treatment
• Known pregnancy or nursing mothers
• Subjects with a fish allergy.
• Subjects with severe asthma defined as asthma not controlled with inhaled corticosteroids and additional controllers or by oral corticosteroid treatment (arginine can cause allergic response or make swelling in airways worse).
• Subjects with a known inherited guanidinoacetate methyltransferase deficiency (due to an inability to convert arginine to creatine)
• Subject with known history of liver cirrhosis
• Subjects who have who have suffered a myocardial infarction or life-threatening arrhythmia within the last 6 months
• Subjects with cardiac failure or coronary artery disease causing unstable angina
• Subjects with a medical or psychological impediment to probable compliance with the protocol should be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Immunonutrition with arginine; Patients will receive the nutritional supplement for 5 days prior to surgery and for 5 days after. The drink will contain arginine.	Dietary supplement: Immunonutrition with arginine; Nutritional beverage containing supplemental arginine taken 3 times per day
PLACEBO_COMPARATOR: Immunonutrition without arginine; This group of patients will also receive a nutritional drink but containing no arginine for 5 days before surgery and for 5 days after surgery.	Dietary supplement: Immunonutrition without Arginine; Nutritional beverage without supplemental arginine taken 3 times per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
NK cell killing as measured on peripheral blood mononuclear cells (PBMC) between the control (placebo) and experimental cohorts, using a standard NK cell killing assay.	Baseline (before surgery), post-operative day 1

Secondary Outcome Measures

Outcome Measure	Time Frame
Decrease in postoperative serum arginine levels between the control (placebo) and experimental cohorts	Baseline (before surgery), post-operative day 1, 3, 5 and 35
Compliance with perioperative arginine supplementation	5 days preoperatively to 5 days postoperatively

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Investigators: Principal Investigator: Rebecca C Auer, MD, MSc, Ottawa Hospital Research Institute

Publications and helpful links

General Publications

• Angka L, Martel AB, Ng J, Pecarskie A, Sadiq M, Jeong A, Scaffidi M, Tanese de Souza C, Kennedy MA, Tadros S, Auer RC. A Translational Randomized Trial of Perioperative Arginine Immunonutrition on Natural Killer Cell Function in Colorectal Cancer Surgery Patients. Ann Surg Oncol. 2022 Nov;29(12):7410-7420. doi: 10.1245/s10434-022-12202-y. Epub 2022 Jul 25.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2017
• Primary Completion (ACTUAL): June 1, 2019
• Study Completion (ACTUAL): July 1, 2019

Study Registration Dates

• First Submitted: October 25, 2016
• First Submitted That Met QC Criteria: December 6, 2016
• First Posted (ESTIMATE): December 8, 2016

Study Record Updates

• Last Update Posted (ACTUAL): September 6, 2019
• Last Update Submitted That Met QC Criteria: September 3, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Surgery; Colorectal Cancer; Arginine Supplementation; Arginine depletion; Immune system dysfunction
• 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: 20160732-01H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

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