Perioperative Immunonutrition in Colorectal Cancer Patients Undergoing Abdominal Surgery

NCT02987296 | Completed DMC

• 1 other identifier: 20160732-01H
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

ColoRectal Cancer

Keywords

Colorectal Cancer; Surgery; Arginine depletion; Immune system dysfunction; Arginine Supplementation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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

Study Arms (2)

Immunonutrition with arginine

ACTIVE COMPARATOR

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

Immunonutrition without arginine

PLACEBO COMPARATOR

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

Interventions

Immunonutrition with arginine DIETARY_SUPPLEMENT

Nutritional beverage containing supplemental arginine taken 3 times per day

Immunonutrition with arginine

Immunonutrition without Arginine DIETARY_SUPPLEMENT

Nutritional beverage without supplemental arginine taken 3 times per day

Immunonutrition without arginine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (1)

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Related Publications (1)

• 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.

  PMID: 35879482 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Immunonutrition Diet; Arginine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Study Officials

• Rebecca C Auer, MD, MSc

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2016
• First Posted: December 8, 2016
• Study Start: March 1, 2017
• Primary Completion: June 1, 2019
• Study Completion: July 1, 2019
• Last Updated: September 6, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will share

Locations

CA (1)