Clinical trial NCT02987296: Perioperative Immunonutrition in Colorectal Cancer Patients Undergoing Abdominal Surgery
Official title: A Translational Clinical Trial of Perioperative Immunonutrition in Colorectal Cancer Patients Undergoing Abdominal Surgery: PERIOP-02
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: ColoRectal Cancer
Keywords: Colorectal Cancer
Surgery
Arginine depletion
Immune system dysfunction
Arginine Supplementation
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
First posted: 2016-12-08
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: Baseline (before surgery), post-operative day 1
Secondary outcomes:
measure: Decrease in postoperative serum arginine levels between the control (placebo) and experimental cohorts
timeFrame: Baseline (before surgery), post-operative day 1, 3, 5 and 35
measure: Compliance with perioperative arginine supplementation
timeFrame: 5 days preoperatively to 5 days postoperatively
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Rebecca C Auer, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.