Pre-Surgical Immunonutrition's Effect on Colorectal Surgery

Impact of Pre-surgical Oral Immunonutrition on Plasma Levels of Branched-chain Amino Acids in Elective Colorectal Surgery Patients: a Randomized, Double-blind, Controlled, Clinical Trial

Colorectal surgery patients face excessive catabolism, increasing inflammation and immune compromise. The administration of nutritional supplements known as immunonutrition before gastrointestinal surgery has been shown to improve clinical outcomes; however, the mechanisms underlying these benefits remain inconclusive.

The objective of the study is to evaluate the effect of preoperative nutritional supplementation with an immunonutrient-enriched formula compared to an isocaloric and isoproteic formula on plasma BCAA concentration in patients undergoing elective colorectal surgery. A double-blind, randomized controlled clinical trial will be conducted. Patients will be required to drink the supplement daily for the 7 days preceding the surgical intervention. Patients in both groups will be instructed to maintain their usual food intake. During the study, there will be two patient assessments and a review of medical records to document the outcomes.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Surgery
• Intervention / Treatment: Dietary supplement: Preoperative oral immunonutrition formula; Dietary supplement: Preoperative oral Isocaloric and isoproteic polymeric formula

Detailed Description

Patients undergoing colorectal surgery, experience excessive and persistent catabolism, leading to skeletal muscle depletion, and increased inflammatory and immunological involvement, this results in greater malnutrition, mortality, and postoperative morbidity. Depletion of amino acids leads to an increased inflammatory response and diminished immunity. Guidelines of leading international societies in the field of clinical nutrition recommend the perioperative administration of oral formulas with immunonutrients in these patients. The administration of nutritional supplements known as immunonutrition (fortified with arginine, glutamine, branched-chain amino acids (BCAAs) and omega-3 polyunsaturated fatty acids) before gastrointestinal surgery has been shown to improve clinical outcomes, such as a reduction in post-surgical infectious, reduced risk of anastomotic leakage and fewer days of hospital stay; however, the mechanisms related to these benefits are not conclusive.

The aim of the study is to evaluate the effect of preoperative nutritional supplementation for 7 days with a formula enriched with immunonutrients compared to an isocaloric and isoproteic formula, on the plasma concentration of BCAAs in patients undergoing elective colorectal surgery. A randomized, double-blind, controlled trial will be conducted with 63 patients per group. The concentration of BCAAs will be measured prior to the 7 days of nutritional supplementation and will be repeated on the day of the surgical intervention before the procedure. The supplements for both groups will provide 500 calories, 41 g of protein, 60 g of carbohydrates, and 11 g of lipids; the supplement for the intervention group is additionally fortified with immunonutrients. Patients will be instructed to consume the supplement daily for the 7 days prior to the surgical intervention. Patients in both groups will be advised to maintain their usual food intake.

The investigators hypothesized that if an oral formula with immunonutrients is administered compared to an isocaloric and isoproteic formula without them for 7 days in the preoperative period in patients undergoing elective colorectal surgery, there will be an increase in the plasma concentration of BCAAs in the intervention group.

• Study Type: Interventional
• Enrollment (Estimated): 126
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Aurora E Serralde Zúñiga, MD, PhD; Phone Number: 2193 +52 5554870900; Email: aurozabeth@yahoo.com.mx

Study Locations

• Mexico
  • Tlalpan
    • Mexico City, Tlalpan, Mexico, 14080
      • Recruiting
      • Aurora E Serralde Zúñiga, MD, PhD
      • Sub-Investigator: Martha Guevara Cruz, MD, PhD
      • Contact: Aurora E Serralde Zúñiga, MD, PhD; Phone Number: 2193 +52 5554870900; Email: aurozabeth@yahoo.com.mx
      • Sub-Investigator: José F Estrada Moya, MSc
      • Sub-Investigator: Luis E González Salazar, PhD
      • Sub-Investigator: Adriana G Flores López, MSc
      • Sub-Investigator: Omar Vergara Fernández, MD
      • Sub-Investigator: Noel Salgado Nesme, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Both sexes
• Over 18 years of age
• Scheduled for elective colorectal surgery (Resection and intestinal reconnection)
• Obtaining patient consent

Exclusion Criteria:

• Consumption of nutritional supplements during the 2 weeks prior to patient enrollment
• Consumption of additional nutritional supplements during the 7 days corresponding to the study intervention period
• Patients diagnosed with chronic kidney disease
• Patients diagnosed with hepatic cirrhosis
• Documented allergy to any of the ingredients in the formulas under evaluation (milk and/or soy).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Arm; Preoperative oral supplementation (immunonutrition)	Dietary supplement: Preoperative oral immunonutrition formula; Intervention arm will daily receive, for 7 days, a preoperative oral formula with immunonutrients: 500 kcal of energy, 41 g of protein, 60 g of carbohydrates, 11 g of lipids, 5.7 g of glutamine, 7 g of arginine, 3.6 g of leucine, 2.7 g of isoleucine, 3.7 g of valine, and 0.35 g of omega 3
Active Comparator: Control Arm; Preoperative oral supplementation (polymeric)	Dietary supplement: Preoperative oral Isocaloric and isoproteic polymeric formula; Control arm will daily receive, for 7 days, an isocaloric and isoproteic preoperative oral formula: 500 kcal of energy, 41 g of protein, 60 g of carbohydrates, and 11 g of lipids

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of branched-chain amino acids	Plasma concentrations of branched-chain amino acids, expressed in micromoles per liter (µmol/L), will be quantified at two distinct time points during the study	The first measurement will be conducted 7 days prior to the surgical intervention (baseline measurement). The second measurement will be performed on the day of the surgical intervention, before the start of the procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of albumin	Serum concentrations of albumin, expressed in grams per deciliter (g/dL), will be quantified at two distinct time points during the study	The first measurement will be conducted 7 days prior to the surgical intervention (baseline measurement). The second measurement will be performed on the day of the surgical intervention, before the start of the procedure
Concentration of high-sensitivity C-reactive protein	Serum concentrations of high-sensitivity C-reactive protein, expressed in milligrams per deciliter (mg/dL), will be quantified at two distinct time points during the study	The first measurement will be conducted 7 days prior to the surgical intervention (baseline measurement). The second measurement will be performed on the day of the surgical intervention, before the start of the procedure
Mortality	The incidence of death within the study population will be recorded and reported throughout the study period following surgery	Mortality will be assessed within 30 days post-surgery
Length of stay	The number of days from the patient's hospital admission to discharge will be recorded and reported during the study period	Length of stay will be assessed within 30 days post-surgery
Hospital readmission	The necessity for rehospitalization after discharge following surgery will be recorded and reported during the study period	Hospital readmission will be assessed within 30 days post-surgery
Anastomotic dehiscence	Occurrence of anastomotic dehiscence within the study population following surgery	Anastomotic dehiscence will be assessed within 30 days post-surgery
Surgical site infection	Occurrence of surgical site infection within the study population following surgery	Surgical site infection will be assessed within 30 days post-surgery
Fistula	Occurrence of fistula within the study population following surgery	Fistula will be assessed within 30 days post-surgery
Paralytic ileus	Occurrence of paralytic ileus within the study population following surgery	Paralytic ileus will be assessed within 30 days post-surgery
Postoperative intestinal obstruction	Occurrence of postoperative intestinal obstruction within the study population following surgery	Postoperative intestinal obstruction will be assessed within 30 days post-surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight	Weight will be measured using a calibrated scale and quantified at two distinct time points during the study and will be reported in kg	The first measurement will be conducted 7 days prior to the surgical intervention (baseline measurement), and the second measurement will be performed on the day of the surgical intervention before the procedure begins
Height	Height will be assessed using a standardized automatic stadiometer and quantified once during the study and will be reported in cm	The measurement will be conducted 7 days prior to the surgical intervention
Body mass index	Body mass index (BMI) will be calculated from the measured weight and height, quantified at two distinct time points during the study and will be reported in kg/m2	The first measurement will be conducted 7 days prior to the surgical intervention (baseline measurement), and the second measurement will be performed on the day of the surgical intervention before the procedure begins
Muscle mass	Muscle mass will be evaluated using a standardized tetrapolar bioelectrical impedance analysis and quantified at two distinct time points during the study and will be reported in % of the body weight	The first measurement will be conducted 7 days prior to the surgical intervention (baseline measurement), and the second measurement will be performed on the day of the surgical intervention before the procedure begins
Fat mass	Fat mass will be evaluated using a standardized tetrapolar bioelectrical impedance analysis and quantified at two distinct time points during the study and will be reported in % of the body weight	The first measurement will be conducted 7 days prior to the surgical intervention (baseline measurement), and the second measurement will be performed on the day of the surgical intervention before the procedure begins
Phase angle	Phase angle will be evaluated using a standardized tetrapolar bioelectrical impedance analysis and quantified at two distinct time points during the study and will be reported in degrees (°)	The first measurement will be conducted 7 days prior to the surgical intervention (baseline measurement), and the second measurement will be performed on the day of the surgical intervention before the procedure begins
Muscle strength	Muscle strength will be measured in the dominant hand using a hand dynamometer following a standardized protocol and quantified at two distinct time points during the study and will be reported in kg	The first measurement will be conducted 7 days prior to the surgical intervention (baseline measurement), and the second measurement will be performed on the day of the surgical intervention before the procedure begins
Calf circumference	Calf circumference will be measured using a standardized, non-stretchable metallic tape with standard anthropometric techniques and quantified at two distinct time points during the study and will be reported in cm	The first measurement will be conducted 7 days prior to the surgical intervention (baseline measurement), and the second measurement will be performed on the day of the surgical intervention before the procedure begins
Mid-arm circumference	Mid-arm circumference will be measured using a standardized, non-stretchable metallic tape with standard anthropometric techniques and quantified at two distinct time points during the study and will be reported in cm	The first measurement will be conducted 7 days prior to the surgical intervention (baseline measurement), and the second measurement will be performed on the day of the surgical intervention before the procedure begins
Abdominal distension	Abdominal distension will be recorded through patient self-report and will be reported as presence or absence	The assessment will be conducted on the day of the surgical intervention before the procedure begins.
Abdominal pain	Abdominal pain will be recorded through patient self-report and will be reported as presence or absence	The assessment will be conducted on the day of the surgical intervention before the procedure begins
Diarrhea	The occurrence of diarrhea will be recorded through patient self-report and will be reported as presence or absence	The assessment will be conducted on the day of the surgical intervention before the procedure begins
Nausea	The occurrence of nausea will be recorded through patient self-report and will be reported as presence or absence	The assessment will be conducted on the day of the surgical intervention before the procedure begins
Vomiting	The occurrence of vomiting will be recorded through patient self-report and will be reported as presence or absence	The assessment will be conducted on the day of the surgical intervention before the procedure begins

Collaborators and Investigators

• Sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Investigators: Principal Investigator: Aurora E Serralde Zúñiga, MD, PhD, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Publications and helpful links

General Publications

• Choudry HA, Pan M, Karinch AM, Souba WW. Branched-chain amino acid-enriched nutritional support in surgical and cancer patients. J Nutr. 2006 Jan;136(1 Suppl):314S-8S. doi: 10.1093/jn/136.1.314S.
• Finco C, Magnanini P, Sarzo G, Vecchiato M, Luongo B, Savastano S, Bortoliero M, Barison P, Merigliano S. Prospective randomized study on perioperative enteral immunonutrition in laparoscopic colorectal surgery. Surg Endosc. 2007 Jul;21(7):1175-9. doi: 10.1007/s00464-007-9238-4. Epub 2007 Mar 14.
• Yu K, Zheng X, Wang G, Liu M, Li Y, Yu P, Yang M, Guo N, Ma X, Bu Y, Peng Y, Han C, Yu K, Wang C. Immunonutrition vs Standard Nutrition for Cancer Patients: A Systematic Review and Meta-Analysis (Part 1). JPEN J Parenter Enteral Nutr. 2020 Jul;44(5):742-767. doi: 10.1002/jpen.1736. Epub 2019 Nov 11.
• Li P, Yin YL, Li D, Kim SW, Wu G. Amino acids and immune function. Br J Nutr. 2007 Aug;98(2):237-52. doi: 10.1017/S000711450769936X. Epub 2007 Apr 3.
• Slim K, Badon F, Vacheron CH, Dziri C, Marquillier T. Efficacy of perioperative immunonutrition in visceral surgery: an umbrella review protocol. BMJ Open. 2021 Sep 13;11(9):e053851. doi: 10.1136/bmjopen-2021-053851.
• Adiamah A, Skorepa P, Weimann A, Lobo DN. The Impact of Preoperative Immune Modulating Nutrition on Outcomes in Patients Undergoing Surgery for Gastrointestinal Cancer: A Systematic Review and Meta-analysis. Ann Surg. 2019 Aug;270(2):247-256. doi: 10.1097/SLA.0000000000003256.
• Niu JW, Zhou L, Liu ZZ, Pei DP, Fan WQ, Ning W. A Systematic Review and Meta-Analysis of the Effects of Perioperative Immunonutrition in Gastrointestinal Cancer Patients. Nutr Cancer. 2021;73(2):252-261. doi: 10.1080/01635581.2020.1749291. Epub 2020 Apr 14.
• Cangiano C, Laviano A, Meguid MM, Mulieri M, Conversano L, Preziosa I, Rossi-Fanelli F. Effects of administration of oral branched-chain amino acids on anorexia and caloric intake in cancer patients. J Natl Cancer Inst. 1996 Apr 17;88(8):550-2. doi: 10.1093/jnci/88.8.550. No abstract available.
• Wischmeyer PE, Carli F, Evans DC, Guilbert S, Kozar R, Pryor A, Thiele RH, Everett S, Grocott M, Gan TJ, Shaw AD, Thacker JKM, Miller TE, Hedrick TL, McEvoy MD, Mythen MG, Bergamaschi R, Gupta R, Holubar SD, Senagore AJ, Abola RE, Bennett-Guerrero E, Kent ML, Feldman LS, Fiore JF Jr; Perioperative Quality Initiative (POQI) 2 Workgroup. American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Nutrition Screening and Therapy Within a Surgical Enhanced Recovery Pathway. Anesth Analg. 2018 Jun;126(6):1883-1895. doi: 10.1213/ANE.0000000000002743.

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2023
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: March 7, 2025
• First Submitted That Met QC Criteria: March 12, 2025
• First Posted (Actual): March 19, 2025

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Enhanced Recovery After Surgery; Immunonutrition; Preoperative Care; Colorectal Surgery; Amino Acids Branched-Chain
• Other Study ID Numbers: 4475

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No