Colorectal CancerNCT07506187
The Role of Arginine in Oral Nutritional Supplementation in Preventing or Reducing Complications Following Colorectal Surgery in Patients Who Are Malnourished or at Risk of Malnutrition
A study testing Diaba plus®: A high-protein, high-calorie ONS with no generic equivalent and Atémpero®: An ONS enriched with arginine with no generic equivalent in people with Colorectal Cancer and Malnutrition or Risk of Malnutrition, run by University of Cadiz at 1 site in Spain.
Trial summary
The goal of this randomized controlled trial is to evaluate the role of a high-calorie, high-protein oral nutritional supplement enriched with arginine in the prevention or reduction of post-surgical complications in adult patients undergoing scheduled colorectal surgery who are malnourished or at risk of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Malnutrition or Risk of Malnutrition, Colorectal Surgery
- What is being tested?
- Diaba plus®: A high-protein, high-calorie ONS with no generic equivalent and Atémpero®: An ONS enriched with arginine with no generic equivalent
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteSpain
- Study dates
- 1 Oct 2022to 31 Jul 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged 18 years or over.
- Patients due to undergo colorectal surgery.
- Patients who are malnourished or at risk of malnutrition prior to surgery.
Who cannot join
- Limitations on oral intake (medical conditions, health status, etc.) or contraindications to oral administration.
- Digestive intolerance or allergy to any of the product's components.
- Emergency colorectal surgery.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Role of Arginine in Oral Nutritional Supplementation in Preventing or Reducing Complications Following Colorectal Surgery in Patients Who Are Malnourished or at Risk of Malnutrition: A Randomized Controlled Trial
The goal of this randomized controlled trial is to evaluate the role of a high-calorie, high-protein oral nutritional supplement enriched with arginine in the prevention or reduction of post-surgical complications in adult patients undergoing scheduled colorectal surgery who are malnourished or at risk of malnutrition.
The main questions it aims to answer are:
Read more
- Does the administration of an arginine-enriched enteral formula decrease the occurrence of post-surgical complications compared to a standard high-protein, high-calorie formula?
- Does the use of an arginine-enriched formula reduce the length of hospital stay and associated healthcare costs?
Researchers will compare a high-protein, high-calorie oral nutritional supplement (ONS) enriched with arginine, omega-3, and nucleotides (Atémpero®) to a standard high-protein, high-calorie ONS without arginine (Diaba plus®) to see if the arginine-enriched formula significantly reduces postoperative complications, such as surgical site infections and dehiscence, as well as the duration of hospital stay.
Participants will:
- Undergo a comprehensive nutritional and clinical assessment, including body composition analysis via bioelectrical impedance and handgrip strength tests.
- Receive individualized oral nutritional supplementation (either the arginine-enriched formula or the standard formula) as part of their preoperative preparation.
- Participate in five follow-up visits (baseline, 24 hours pre-surgery, 24 hours post-surgery, 5 days post-surgery, and 30 days post-surgery) for anthropometric, biochemical, and clinical monitoring.
Read the detailed description
Overview This randomized controlled trial (RCT) aims to investigate whether a specific nutritional strategy can improve recovery for adults undergoing scheduled colorectal surgery. Specifically, the study focuses on patients who are malnourished or at risk of malnutrition, a condition affecting 45% to 60% of individuals with colorectal cancer. Malnutrition is a significant concern in surgical settings because it often leads to increased postoperative complications, such as impaired wound healing and higher rates of infection, which ultimately result in longer hospital stays and increased healthcare costs.
Background Maintaining an optimal nutritional status is a critical component of modern surgical protocols, including Enhanced Recovery After Surgery (ERAS). While standard high-protein, high-calorie supplements are frequently used, there is ongoing debate within the medical community regarding the added benefits of "immunonutrients"-specialized ingredients like arginine. Arginine is an amino acid that plays a vital role in collagen synthesis and immune system activation, both of which are essential for proper healing and the prevention of infections. This study seeks to determine if adding arginine to a standard nutritional regimen provides superior outcomes compared to standard supplementation alone.
Methodology
To ensure rigorous results, participants are divided into three distinct groups:
- Control Group: Patients who are well-nourished and do not require specialized supplementation.
- Standard Intervention Group: Malnourished patients receiving a standard high-protein, high-calorie oral nutritional supplement (ONS).
- Arginine-Enriched Group: Malnourished patients receiving a high-protein, high-calorie ONS enriched with arginine, omega-3 fatty acids, and nucleotides.
All participants undergo a comprehensive clinical and nutritional assessment. This includes bioelectrical impedance analysis to measure body composition (such as muscle mass, fat percentage, and hydration levels) and handgrip strength tests to evaluate physical function and muscle quality. The study follows a structured timeline involving five key evaluation points:
- Baseline (Visit 0): Initial diagnosis of malnutrition and the start of the personalized nutritional intervention.
- Pre-Surgery (Visit 1): A final check 24 hours before the operation to monitor blood markers and nutritional status.
- Early Post-Surgery (Visits 2 \& 3): Monitoring for immediate complications 24 hours and five days after the procedure.
- Long-term Follow-Up (Visit 4): A final assessment 30 days after surgery to evaluate overall recovery and quality of life.
Key Outcomes and Expected Impact The primary objective is to determine if the arginine-enriched formula significantly reduces surgical site infections, suture dehiscence (the reopening of a surgical wound), and other common postoperative issues. Furthermore, the research team is tracking the duration of hospital stays and associated healthcare expenses to evaluate if specialized nutrition is a cost-effective way to improve patient care. Ultimately, these findings could refine clinical guidelines, helping patients recover more quickly and effectively, thereby improving their overall quality of life.
- Being tested
- Diaba plus®: A high-protein, high-calorie ONS with no generic equivalent, Atémpero®: An ONS enriched with arginine with no generic equivalent
- Keywords
- Arginine-enriched oral nutritional supplementation, Immunonutrition, High-protein, high-calorie formula, Nutritional screening and diagnosis, Length of hospital stay
- Medical subject headings
- Colorectal Neoplasms, Malnutrition, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Diaba plus®: A high-protein, high-calorie ONS with no generic equivalentDietary supplement
It is a complete high-protein, high-calorie formula containing a blend of fibre, indicated for malnourished patients with stress-induced hyperglycaemia and/or diabetes who have increased protein and/or energy requirements. No risks have been identified during the administration of this formula. It is available in 200 mL bottles (vanilla, cocoa and coffee flavours).
Atémpero®: An ONS enriched with arginine with no generic equivalentDietary supplement
It is a complete, high-protein, high-calorie formula containing a fibre blend enriched with omega-3, L-arginine and nucleotides, and providing vitamin C and zinc. This formula is specifically designed for malnourished patients with wounds or in preparation for surgery. No risks have been identified during the administration of this formula, and it is in line with guidelines for the management of malnourished patients with wounds or those due to undergo colorectal surgery. It is available in a 200 mL format (vanilla flavour). The nutritional information is provided below.
| Study group | Role | What they receive |
|---|---|---|
| Arginine-Enriched Group | Experimental | Malnourished patients receiving a high-protein, high-calorie ONS enriched with arginine, omega-3 fatty acids, and nucleotides. Receives: Dietary Supplement: Atémpero®: An ONS enriched with arginine with no generic equivalent |
| Standard Intervention Group | Active comparator | Malnourished patients receiving a standard high-protein, high-calorie oral nutritional supplement (ONS). Receives: Dietary Supplement: Diaba plus®: A high-protein, high-calorie ONS with no generic equivalent |
| Control Group | No intervention | Patients who are well-nourished and do not require specialized supplementation. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Presence of Postoperative Complications
This dependent variable tracks whether a patient experiences any medical or surgical complications following colorectal surgery. It is recorded as a binary outcome (Yes/No) and serves as the main indicator of the intervention's success in improving patient recovery.
Measured: At 24 hours after the procedure and 30 days after surgery.
Surgical Site Infection
An infection occurring at the site of the surgical incision or in the surrounding tissues within the first 30 to 90 days after the procedure. It is assessed using standardized clinical criteria and recorded as Yes or No.
Measured: From the date of surgery to 30 or 90 days postoperatively, depending on the procedure.
Postoperative Intestinal Ileus
A temporary failure of the intestines to resume normal muscle contractions (peristalsis) after surgery, which prevents the passage of food and waste. It is recorded as Yes or No based on clinical observation.
Measured: At 24 hours after the procedure and 30 days after surgery.
Intra-abdominal Collection (Abscess)
A localized accumulation of pus within the abdominal cavity. It is confirmed by the presence of bacteria in a clinical smear or by positive growth in a bacterial culture. Dichotomous qualitative variable: Yes / No.
Measured: At 24 hours after the procedure and 30 days after surgery.
Intestinal Ischemia
A serious condition occurring when blood flow to the intestines is reduced due to a blockage in a blood vessel, typically an artery, which can lead to tissue damage or death. Dichotomous qualitative variable: Yes / No.
Measured: At 24 hours after the procedure and 30 days after surgery.
Intestinal Evisceration
The protrusion of internal abdominal organs (such as the intestines) through a surgical wound that has reopened across all layers of the abdominal wall following a laparotomy. Dichotomous qualitative variable: Yes / No.
Measured: At 24 hours after the procedure and 30 days after surgery.
Bacteremia
The clinical presence of viable bacteria in the patient's bloodstream, typically identified through blood cultures. Dichotomous qualitative variable: Yes / No.
Measured: At 24 hours after the procedure and 30 days after surgery.
Suture Dehiscence
The failure or reopening of a surgical wound or an internal connection (anastomosis) where tissues were joined by sutures, allowing the edges to separate. Dichotomous qualitative variable: Yes / No.
Measured: At 24 hours after the procedure and 30 days after surgery.
Phlebitis
Inflammation of the walls of a vein, which can occur as a complication of intravenous therapy or the surgical process. Dichotomous qualitative variable: Yes / No.
Measured: At 24 hours after the procedure and 30 days after surgery.
Urinary Tract Infection
An infection occurring in the urinary system (urethra, bladder, or kidneys), common in surgical settings when bacteria enter the urinary tract. Dichotomous qualitative variable: Yes / No.
Measured: At 24 hours after the procedure and 30 days after surgery.
Pneumonia
An infection that inflames the air sacs in one or both lungs, which may fill with fluid or pus, often caused by bacterial or viral infection during the recovery period. Dichotomous qualitative variable: Yes / No.
Measured: At 24 hours after the procedure and 30 days after surgery.
Atelectasis
A complete or partial collapse of the lung or a section of the lung, which occurs when the small air sacs (alveoli) become deflated, frequently due to increased intra-abdominal pressure during surgery. Dichotomous qualitative variable: Yes / No.
Measured: At 24 hours after the procedure and 30 days after surgery.
Secondary outcomes (37)
Biological Sex
Classification of the participant as male or female.
Measured: At enrollment (baseline).
Age
The chronological age of the participant measured in years at the time of study entry.
Measured: At enrollment (baseline).
Clinical Judgment
A professional medical assessment of the patient's current health status. Nominal qualitative variable.
Measured: At enrollment (baseline).
Prior Pathologies
A record of pre-existing chronic conditions or previous illnesses. Nominal qualitative variable.
Measured: At enrollment (baseline).
Functional Independence
A validated tool (Barthel Index) used to measure a patient's performance in activities of daily living (ADLs). It assesses aspects such as eating, washing, dressing, toilet training and mobility. The score ranges from 0 (total dependence) to 100 (total independence).
Measured: At enrollment (baseline) and 30 days after surgery.
Handgrip Strength
A measure of upper body muscle strength and physical function, obtained using a calibrated hydraulic hand dynamometer.
Measured: At enrollment (baseline) and 30 days after surgery.
Nutritional status
A standardized screening tool (Malnutrition Universal Screening Tool, MUST) used to identify adults at risk of malnutrition based on Body Mass Index (BMI), unintentional weight loss, and the presence of acute disease.
Measured: At enrollment (baseline), 24 hours before the procedure, and 30 days after surgery.
Nutritional Control Index
An objective screening score used to identify the risk of malnutrition based on three laboratory parameters: serum albumin, total cholesterol, and total lymphocyte count. Discrete quantitative variable and categorical qualitative variable: risk of malnutrition (no risk, mild, moderate, severe).
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Malnutrition Diagnosis
A diagnostic framework for malnutrition that requires at least one phenotypic criterion (weight loss, low BMI, or reduced muscle mass) and one etiologic criterion (reduced food intake/assimilation or inflammation). Categorical qualitative variable: moderate malnutrition or severe malnutrition.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Fat mass percentage
An assessment of body tissues measured using an Akern BIA 101 device (50kHz), which calculates resistance to a low-intensity electrical current.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Fat-free mass percentage
An assessment of body tissues measured using an Akern BIA 101 device (50kHz), which calculates resistance to a low-intensity electrical current.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Total body water
An assessment of body tissues measured using an Akern BIA 101 device (50kHz), which calculates resistance to a low-intensity electrical current. Unit: L.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Phase Angle
A prognostic indicator of cellular health and integrity derived from bioelectrical impedance analysis.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Body Mass Index
A calculation of body fat based on the patient's height and weight, expressed in kg/m².
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Dietary Intake Percentage
A categorical estimation of the amount of prescribed food and supplements consumed, recorded as 25%, 50%, 75%, or 100%.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Intervention Adherence
A record of whether the patient consistently followed the prescribed oral nutritional supplement protocol (Yes/No).
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Type of diet
Diet followed by the participant. Nominal qualitative variable.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Hemoglobin
Measured in g/dL.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Glucose
Measured in mg/dL.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Urea
Measured in mg/dL.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Creatinine
Measured in mg/dL.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Total Cholesterol
Measured in mg/dL.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Triglycerides
Measured in mg/dL.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Total Proteins
Measured in g/dL.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Sodium
Measured in mg/dL.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Potassium
Measured in mg/dL.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Total Lymphocyte Count
Measured in cells/µl.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Serum Albumin
Specific biochemical marker used to evaluate protein status and monitor the effectiveness of nutritional support. Measured in g/dL.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Prealbumin
Specific biochemical marker used to evaluate protein status and monitor the effectiveness of nutritional support. Measured in mg/dL.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Hospital Length of Stay
The total number of days the patient remains hospitalized. Discrete numerical variable.
Measured: From the day of hospital admission for surgery until discharge.
Healthcare Costs
The direct financial costs associated with their care, used to assess the economic impact of the nutritional intervention. Continuous quantitative variable: economic costs (€ and $).
Measured: From the day of hospital admission for surgery until discharge.
Extracellular water
An assessment of body tissues measured using an Akern BIA 101 device (50kHz), which calculates resistance to a low-intensity electrical current. Unit: L.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Intracellular water
An assessment of body tissues measured using an Akern BIA 101 device (50kHz), which calculates resistance to a low-intensity electrical current. Unit: L.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Cell mass
An assessment of body tissues measured using an Akern BIA 101 device (50kHz), which calculates resistance to a low-intensity electrical current. Unit: Kg.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Limb muscle mass
An assessment of body tissues measured using an Akern BIA 101 device (50kHz), which calculates resistance to a low-intensity electrical current. Unit: Kg.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Muscle mass index
An assessment of body tissues measured using an Akern BIA 101 device (50kHz), which calculates resistance to a low-intensity electrical current. Unit: Kg.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Moisture content percentage
An assessment of body tissues measured using an Akern BIA 101 device (50kHz), which calculates resistance to a low-intensity electrical current.
Measured: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2026
- Study start1 Oct 2022
- Primary completion30 Jun 2025
- Study completion31 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cadiz
- Sponsor type
- University, hospital or other
- Collaborators
- Andalusian Health Service, Universidad de Granada
- Responsible party
- Principal investigator, Antonio Jesús Marín Paz, University of Cadiz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07506187
- Sponsor's protocol ID
- PEIBA 0655-N-22
- Status last verified
- Mar 2026
- First submitted
- 26 Mar 2026
- Last updated
- 1 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The dataset containing the collected data, whilst ensuring the anonymity of the participants, will be made publicly available upon publication of the results.
Publications
Leon Sanz M. [A critical review of the GLIM criteria]. Nutr Hosp. 2021 Apr 12;38(Spec No1):29-33. doi: 10.20960/nh.03558. Spanish.
PubMed 33525881Gomes-Neto AW, van Vliet IMY, Oste MCJ, de Jong MFC, Bakker SJL, Jager-Wittenaar H, Navis GJ. Malnutrition Universal Screening Tool and Patient-Generated Subjective Global Assessment Short Form and their predictive validity in hospitalized patients. Clin Nutr ESPEN. 2021 Oct;45:252-261. doi: 10.1016/j.clnesp.2021.08.015. Epub 2021 Sep 3.
PubMed 34620325Osland E, Hossain MB, Khan S, Memon MA. Effect of timing of pharmaconutrition (immunonutrition) administration on outcomes of elective surgery for gastrointestinal malignancies: a systematic review and meta-analysis. JPEN J Parenter Enteral Nutr. 2014 Jan;38(1):53-69. doi: 10.1177/0148607112474825. Epub 2013 Feb 14.
PubMed 23411423Pan YP, Chang PH, Fan CW, Tseng WK, Huang JS, Chen CH, Chou WC, Wang CH, Yeh KY. Relationship between pre-treatment nutritional status, serum glutamine, arginine levels and clinicopathological features in Taiwan colorectal cancer patients. Asia Pac J Clin Nutr. 2015;24(4):598-604. doi: 10.6133/apjcn.2015.24.4.23.
PubMed 26693743Bistrian BR. The role of preoperative immune modulating nutrition. Hepatobiliary Surg Nutr. 2020 Apr;9(2):221-222. doi: 10.21037/hbsn.2019.09.16. No abstract available.
PubMed 32355685Fujiwara T, Kanazawa S, Ichibori R, Tanigawa T, Magome T, Shingaki K, Miyata S, Tohyama M, Hosokawa K. L-arginine stimulates fibroblast proliferation through the GPRC6A-ERK1/2 and PI3K/Akt pathway. PLoS One. 2014 Mar 20;9(3):e92168. doi: 10.1371/journal.pone.0092168. eCollection 2014.
PubMed 24651445Ellinger S, Stehle P. Efficacy of vitamin supplementation in situations with wound healing disorders: results from clinical intervention studies. Curr Opin Clin Nutr Metab Care. 2009 Nov;12(6):588-95. doi: 10.1097/MCO.0b013e328331a5b5.
PubMed 19770648Liu P, Shen WQ, Chen HL. Efficacy of arginine-enriched enteral formulas for the healing of pressure ulcers: a systematic review. J Wound Care. 2017 Jun 2;26(6):319-323. doi: 10.12968/jowc.2017.26.6.319.
PubMed 28598762Mostafavinia A, Bidram M, Gomi Avili A, Mahmanzar M, Karimifard SA, Sajadi E, Amini A, Hadipour Jahromy M, Ghoreishi SK, Chien S, Bayat M. An improvement in acute wound healing in rats by the synergistic effect of photobiomodulation and arginine. Lab Anim Res. 2019 Dec 11;35:28. doi: 10.1186/s42826-019-0025-x. eCollection 2019.
PubMed 32257915Barchitta M, Maugeri A, Favara G, Magnano San Lio R, Evola G, Agodi A, Basile G. Nutrition and Wound Healing: An Overview Focusing on the Beneficial Effects of Curcumin. Int J Mol Sci. 2019 Mar 5;20(5):1119. doi: 10.3390/ijms20051119.
PubMed 30841550Ma C, Tsai H, Su W, Sun L, Shih Y, Wang J. Combination of arginine, glutamine, and omega-3 fatty acid supplements for perioperative enteral nutrition in surgical patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST): A prospective, randomized, double-blind study. J Postgrad Med. 2018 Jul-Sep;64(3):155-163. doi: 10.4103/jpgm.JPGM_693_17.
PubMed 29848836Hegazi RA, Hustead DS, Evans DC. Preoperative standard oral nutrition supplements vs immunonutrition: results of a systematic review and meta-analysis. J Am Coll Surg. 2014 Nov;219(5):1078-87. doi: 10.1016/j.jamcollsurg.2014.06.016. Epub 2014 Jun 27. No abstract available.
PubMed 25260681Gomez Sanchez MB, Garcia-Talavera Espin NV, Sanchez Alvarez C, Zomeno Ros AI, Hernandez MN, Gomez Ramos MJ, Parra Banos P, Gonzalez Valverde FM. [Perioperative nutritional support in patients with colorectal neoplasms]. Nutr Hosp. 2010 Sep-Oct;25(5):797-805. Spanish.
PubMed 21336438Adiamah 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.
PubMed 30817349Yeung SE, Hilkewich L, Gillis C, Heine JA, Fenton TR. Protein intakes are associated with reduced length of stay: a comparison between Enhanced Recovery After Surgery (ERAS) and conventional care after elective colorectal surgery. Am J Clin Nutr. 2017 Jul;106(1):44-51. doi: 10.3945/ajcn.116.148619. Epub 2017 May 3.
PubMed 28468890
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Arginine in Oral Nutritional Supplementation in Preventing or Reducing Complications Following Colorectal Surgery in Patients Who Are Malnourished or at Risk of Malnutrition: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07506187
- Acronym / sponsor ID
- PEIBA 0655-N-22
- Keywords
- Arginine-enriched oral nutritional supplementation, Immunonutrition, High-protein, high-calorie formula, Nutritional screening and diagnosis, Length of hospital stay
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- University of CadizUniversity, hospital or other
- Collaborators
- Andalusian Health Service, Universidad de Granada
- Study start
- 1 Oct 2022 (actual)
- Primary completion
- 30 Jun 2025 (actual)
- Study completion
- 31 Jul 2025 (actual)
- First posted
- 1 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this randomized controlled trial is to evaluate the role of a high-calorie, high-protein oral nutritional supplement enriched with arginine in the prevention or reduction of post-surgical complications in adult patients undergoing scheduled colorectal surgery who are malnourished or at risk of malnutrition.
The main questions it aims to answer are:
- Does the administration of an arginine-enriched enteral formula decrease the occurrence of post-surgical complications compared to a standard high-protein, high-calorie formula?
- Does the use of an arginine-enriched formula reduce the length of hospital stay and associated healthcare costs?
Researchers will compare a high-protein, high-calorie oral nutritional supplement (ONS) enriched with arginine, omega-3, and nucleotides (Atémpero®) to a standard high-protein, high-calorie ONS without arginine (Diaba plus®) to see if the arginine-enriched formula significantly reduces postoperative complications, such as surgical site infections and dehiscence, as well as the duration of hospital stay.
Participants will:
- Undergo a comprehensive nutritional and clinical assessment, including body composition analysis via bioelectrical impedance and handgrip strength tests.
- Receive individualized oral nutritional supplementation (either the arginine-enriched formula or the standard formula) as part of their preoperative preparation.
- Participate in five follow-up visits (baseline, 24 hours pre-surgery, 24 hours post-surgery, 5 days post-surgery, and 30 days post-surgery) for anthropometric, biochemical, and clinical monitoring.
Detailed description
Overview This randomized controlled trial (RCT) aims to investigate whether a specific nutritional strategy can improve recovery for adults undergoing scheduled colorectal surgery. Specifically, the study focuses on patients who are malnourished or at risk of malnutrition, a condition affecting 45% to 60% of individuals with colorectal cancer. Malnutrition is a significant concern in surgical settings because it often leads to increased postoperative complications, such as impaired wound healing and higher rates of infection, which ultimately result in longer hospital stays and increased healthcare costs.
Background Maintaining an optimal nutritional status is a critical component of modern surgical protocols, including Enhanced Recovery After Surgery (ERAS). While standard high-protein, high-calorie supplements are frequently used, there is ongoing debate within the medical community regarding the added benefits of "immunonutrients"-specialized ingredients like arginine. Arginine is an amino acid that plays a vital role in collagen synthesis and immune system activation, both of which are essential for proper healing and the prevention of infections. This study seeks to determine if adding arginine to a standard nutritional regimen provides superior outcomes compared to standard supplementation alone.
Methodology
To ensure rigorous results, participants are divided into three distinct groups:
- Control Group: Patients who are well-nourished and do not require specialized supplementation.
- Standard Intervention Group: Malnourished patients receiving a standard high-protein, high-calorie oral nutritional supplement (ONS).
- Arginine-Enriched Group: Malnourished patients receiving a high-protein, high-calorie ONS enriched with arginine, omega-3 fatty acids, and nucleotides.
All participants undergo a comprehensive clinical and nutritional assessment. This includes bioelectrical impedance analysis to measure body composition (such as muscle mass, fat percentage, and hydration levels) and handgrip strength tests to evaluate physical function and muscle quality. The study follows a structured timeline involving five key evaluation points:
- Baseline (Visit 0): Initial diagnosis of malnutrition and the start of the personalized nutritional intervention.
- Pre-Surgery (Visit 1): A final check 24 hours before the operation to monitor blood markers and nutritional status.
- Early Post-Surgery (Visits 2 \& 3): Monitoring for immediate complications 24 hours and five days after the procedure.
- Long-term Follow-Up (Visit 4): A final assessment 30 days after surgery to evaluate overall recovery and quality of life.
Key Outcomes and Expected Impact The primary objective is to determine if the arginine-enriched formula significantly reduces surgical site infections, suture dehiscence (the reopening of a surgical wound), and other common postoperative issues. Furthermore, the research team is tracking the duration of hospital stays and associated healthcare expenses to evaluate if specialized nutrition is a cost-effective way to improve patient care. Ultimately, these findings could refine clinical guidelines, helping patients recover more quickly and effectively, thereby improving their overall quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arginine-Enriched Group | Experimental | Dietary Supplement: Atémpero®: An ONS enriched with arginine with no generic equivalentMalnourished patients receiving a high-protein, high-calorie ONS enriched with arginine, omega-3 fatty acids, and nucleotides. |
| Standard Intervention Group | Active comparator | Dietary Supplement: Diaba plus®: A high-protein, high-calorie ONS with no generic equivalentMalnourished patients receiving a standard high-protein, high-calorie oral nutritional supplement (ONS). |
| Control Group | No intervention | –Patients who are well-nourished and do not require specialized supplementation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients aged 18 years or over.
- Patients due to undergo colorectal surgery.
- Patients who are malnourished or at risk of malnutrition prior to surgery.
Key exclusion criteria (3 listed)
- Limitations on oral intake (medical conditions, health status, etc.) or contraindications to oral administration.
- Digestive intolerance or allergy to any of the product's components.
- Emergency colorectal surgery.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Diaba plus®: A high-protein, high-calorie ONS with no generic equivalentIt is a complete high-protein, high-calorie formula containing a blend of fibre, indicated for malnourished patients with stress-induced hyperglycaemia and/or diabetes who have increased protein and/or energy requirements. No risks have been identified during the administration of this formula. It is available in 200 mL bottles (vanilla, cocoa and coffee flavours). | Dietary supplement | Standard Intervention Group |
| Atémpero®: An ONS enriched with arginine with no generic equivalentIt is a complete, high-protein, high-calorie formula containing a fibre blend enriched with omega-3, L-arginine and nucleotides, and providing vitamin C and zinc. This formula is specifically designed for malnourished patients with wounds or in preparation for surgery. No risks have been identified during the administration of this formula, and it is in line with guidelines for the management of malnourished patients with wounds or those due to undergo colorectal surgery. It is available in a 200 mL format (vanilla flavour). The nutritional information is provided below. | Dietary supplement | Arginine-Enriched Group |
Primary outcome
Presence of Postoperative Complications
Time frame: At 24 hours after the procedure and 30 days after surgery.
This dependent variable tracks whether a patient experiences any medical or surgical complications following colorectal surgery. It is recorded as a binary outcome (Yes/No) and serves as the main indicator of the intervention's success in improving patient recovery.
Surgical Site Infection
Time frame: From the date of surgery to 30 or 90 days postoperatively, depending on the procedure.
An infection occurring at the site of the surgical incision or in the surrounding tissues within the first 30 to 90 days after the procedure. It is assessed using standardized clinical criteria and recorded as Yes or No.
Postoperative Intestinal Ileus
Time frame: At 24 hours after the procedure and 30 days after surgery.
A temporary failure of the intestines to resume normal muscle contractions (peristalsis) after surgery, which prevents the passage of food and waste. It is recorded as Yes or No based on clinical observation.
Intra-abdominal Collection (Abscess)
Time frame: At 24 hours after the procedure and 30 days after surgery.
A localized accumulation of pus within the abdominal cavity. It is confirmed by the presence of bacteria in a clinical smear or by positive growth in a bacterial culture. Dichotomous qualitative variable: Yes / No.
Intestinal Ischemia
Time frame: At 24 hours after the procedure and 30 days after surgery.
A serious condition occurring when blood flow to the intestines is reduced due to a blockage in a blood vessel, typically an artery, which can lead to tissue damage or death. Dichotomous qualitative variable: Yes / No.
Intestinal Evisceration
Time frame: At 24 hours after the procedure and 30 days after surgery.
The protrusion of internal abdominal organs (such as the intestines) through a surgical wound that has reopened across all layers of the abdominal wall following a laparotomy. Dichotomous qualitative variable: Yes / No.
Bacteremia
Time frame: At 24 hours after the procedure and 30 days after surgery.
The clinical presence of viable bacteria in the patient's bloodstream, typically identified through blood cultures. Dichotomous qualitative variable: Yes / No.
Suture Dehiscence
Time frame: At 24 hours after the procedure and 30 days after surgery.
The failure or reopening of a surgical wound or an internal connection (anastomosis) where tissues were joined by sutures, allowing the edges to separate. Dichotomous qualitative variable: Yes / No.
Phlebitis
Time frame: At 24 hours after the procedure and 30 days after surgery.
Inflammation of the walls of a vein, which can occur as a complication of intravenous therapy or the surgical process. Dichotomous qualitative variable: Yes / No.
Urinary Tract Infection
Time frame: At 24 hours after the procedure and 30 days after surgery.
An infection occurring in the urinary system (urethra, bladder, or kidneys), common in surgical settings when bacteria enter the urinary tract. Dichotomous qualitative variable: Yes / No.
Pneumonia
Time frame: At 24 hours after the procedure and 30 days after surgery.
An infection that inflames the air sacs in one or both lungs, which may fill with fluid or pus, often caused by bacterial or viral infection during the recovery period. Dichotomous qualitative variable: Yes / No.
Atelectasis
Time frame: At 24 hours after the procedure and 30 days after surgery.
A complete or partial collapse of the lung or a section of the lung, which occurs when the small air sacs (alveoli) become deflated, frequently due to increased intra-abdominal pressure during surgery. Dichotomous qualitative variable: Yes / No.
37 secondary outcomes
Biological Sex
Time frame: At enrollment (baseline).
Age
Time frame: At enrollment (baseline).
Clinical Judgment
Time frame: At enrollment (baseline).
Prior Pathologies
Time frame: At enrollment (baseline).
Functional Independence
Time frame: At enrollment (baseline) and 30 days after surgery.
Handgrip Strength
Time frame: At enrollment (baseline) and 30 days after surgery.
Nutritional status
Time frame: At enrollment (baseline), 24 hours before the procedure, and 30 days after surgery.
Nutritional Control Index
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Malnutrition Diagnosis
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Fat mass percentage
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Fat-free mass percentage
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Total body water
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Phase Angle
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Body Mass Index
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Dietary Intake Percentage
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Intervention Adherence
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Type of diet
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Hemoglobin
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Glucose
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Urea
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Creatinine
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Total Cholesterol
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Triglycerides
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Total Proteins
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Sodium
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Potassium
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Total Lymphocyte Count
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Serum Albumin
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Prealbumin
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Hospital Length of Stay
Time frame: From the day of hospital admission for surgery until discharge.
Healthcare Costs
Time frame: From the day of hospital admission for surgery until discharge.
Extracellular water
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Intracellular water
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Cell mass
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Limb muscle mass
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Muscle mass index
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Moisture content percentage
Time frame: At enrollment (baseline), 24 hours before surgery, 5 days after surgery, and 30 days after surgery.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2026.
- Background: PubMed 33525881Leon Sanz M. [A critical review of the GLIM criteria]. Nutr Hosp. 2021 Apr 12;38(Spec No1):29-33. doi: 10.20960/nh.03558. Spanish.
- Background: PubMed 34620325Gomes-Neto AW, van Vliet IMY, Oste MCJ, de Jong MFC, Bakker SJL, Jager-Wittenaar H, Navis GJ. Malnutrition Universal Screening Tool and Patient-Generated Subjective Global Assessment Short Form and their predictive validity in hospitalized patients. Clin Nutr ESPEN. 2021 Oct;45:252-261. doi: 10.1016/j.clnesp.2021.08.015. Epub 2021 Sep 3.
- Background: PubMed 23411423Osland E, Hossain MB, Khan S, Memon MA. Effect of timing of pharmaconutrition (immunonutrition) administration on outcomes of elective surgery for gastrointestinal malignancies: a systematic review and meta-analysis. JPEN J Parenter Enteral Nutr. 2014 Jan;38(1):53-69. doi: 10.1177/0148607112474825. Epub 2013 Feb 14.
- Background: PubMed 26693743Pan YP, Chang PH, Fan CW, Tseng WK, Huang JS, Chen CH, Chou WC, Wang CH, Yeh KY. Relationship between pre-treatment nutritional status, serum glutamine, arginine levels and clinicopathological features in Taiwan colorectal cancer patients. Asia Pac J Clin Nutr. 2015;24(4):598-604. doi: 10.6133/apjcn.2015.24.4.23.
- Background: PubMed 32355685Bistrian BR. The role of preoperative immune modulating nutrition. Hepatobiliary Surg Nutr. 2020 Apr;9(2):221-222. doi: 10.21037/hbsn.2019.09.16. No abstract available.
- Background: PubMed 24651445Fujiwara T, Kanazawa S, Ichibori R, Tanigawa T, Magome T, Shingaki K, Miyata S, Tohyama M, Hosokawa K. L-arginine stimulates fibroblast proliferation through the GPRC6A-ERK1/2 and PI3K/Akt pathway. PLoS One. 2014 Mar 20;9(3):e92168. doi: 10.1371/journal.pone.0092168. eCollection 2014.
- Background: PubMed 19770648Ellinger S, Stehle P. Efficacy of vitamin supplementation in situations with wound healing disorders: results from clinical intervention studies. Curr Opin Clin Nutr Metab Care. 2009 Nov;12(6):588-95. doi: 10.1097/MCO.0b013e328331a5b5.
- Background: PubMed 28598762Liu P, Shen WQ, Chen HL. Efficacy of arginine-enriched enteral formulas for the healing of pressure ulcers: a systematic review. J Wound Care. 2017 Jun 2;26(6):319-323. doi: 10.12968/jowc.2017.26.6.319.
- Background: PubMed 32257915Mostafavinia A, Bidram M, Gomi Avili A, Mahmanzar M, Karimifard SA, Sajadi E, Amini A, Hadipour Jahromy M, Ghoreishi SK, Chien S, Bayat M. An improvement in acute wound healing in rats by the synergistic effect of photobiomodulation and arginine. Lab Anim Res. 2019 Dec 11;35:28. doi: 10.1186/s42826-019-0025-x. eCollection 2019.
- Background: PubMed 30841550Barchitta M, Maugeri A, Favara G, Magnano San Lio R, Evola G, Agodi A, Basile G. Nutrition and Wound Healing: An Overview Focusing on the Beneficial Effects of Curcumin. Int J Mol Sci. 2019 Mar 5;20(5):1119. doi: 10.3390/ijms20051119.
- Background: PubMed 29848836Ma C, Tsai H, Su W, Sun L, Shih Y, Wang J. Combination of arginine, glutamine, and omega-3 fatty acid supplements for perioperative enteral nutrition in surgical patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST): A prospective, randomized, double-blind study. J Postgrad Med. 2018 Jul-Sep;64(3):155-163. doi: 10.4103/jpgm.JPGM_693_17.
- Background: PubMed 25260681Hegazi RA, Hustead DS, Evans DC. Preoperative standard oral nutrition supplements vs immunonutrition: results of a systematic review and meta-analysis. J Am Coll Surg. 2014 Nov;219(5):1078-87. doi: 10.1016/j.jamcollsurg.2014.06.016. Epub 2014 Jun 27. No abstract available.
- Individual participant dataSharing planned: Yes. The dataset containing the collected data, whilst ensuring the anonymity of the participants, will be made publicly available upon publication of the results.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Diaba plus®: A high-protein, high-calorie ONS with no generic equivalent and Atémpero®: An ONS enriched with arginine with no generic equivalent in people with Colorectal Cancer and Malnutrition or Risk of Malnutrition, run by University of Cadiz at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Presence of Postoperative Complications (time frame: At 24 hours after the procedure and 30 days after surgery.). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07506187, which also lists 20 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2026.