NIMA-Colon Cancer Study

Colon cancer patients frequently present with nutritional impairment, systemic inflammation, and early loss of muscle mass even before surgical treatment. These conditions may be exacerbated by surgical stress, reduced intake, and postoperative physical inactivity, leading to delayed recovery, functional decline, and impaired quality of life. Interventions targeting nutritional and functional status across the perioperative period may help improve physiological reserve and support postoperative recovery.

The NIMA study (Nutritional, Inflammatory, and Muscular Assessment) is designed to evaluate the impact of perioperative nutritional care and postoperative physical activity strategies on recovery, muscle strength, nutritional status, inflammation, metabolic health, and gut microbiota in adults undergoing surgery for colon cancer. The study combines routine preoperative nutritional management with a structured postoperative intervention and follow-up period, allowing assessment of short- and medium-term changes during recovery.

Study Setting and Population: This study includes adult patients diagnosed with colon cancer stages I to III, (TNM classification) who undergo surgical treatment at the Hospital Universitario Virgen de la Victoria in Málaga, Spain. Participants are identified and recruited before surgery through standard clinical pathways. All participants provide written informed consent before enrollment. The study is conducted in accordance with ethical principles and has been approved by the appropriate ethics committee.

Prehabilitation Phase (Preoperative Nutritional Care): Approximately two weeks before surgery, patients undergo a prehabilitation phase integrated into routine clinical care provided by the Endocrinology and Nutrition Department. This phase includes assessment and optimization of nutritional status through clinical evaluation, follow-up, and oral hypercaloric and hyperproteic supplementation when indicated. The aim is to improve metabolic condition and physiological reserve prior to surgical stress.

Surgical Treatment and Standard Postoperative Care: All participants undergo standard surgical treatment and postoperative oncological management according to institutional clinical practice. Participation in the study does not modify surgical procedures, immediate postoperative care, or oncological treatment.

Postoperative Interventions(Factorial Design): Approximately one month after surgery, once initial postoperative recovery has been achieved, participants enter the intervention phase (baseline visit). Participants are randomly assigned to one of four study groups according to a 2×2 factorial design:

* Standard nutritional care + general physical activity recommendations * Standard nutritional care + supervised exercise program * Enhanced nutritional supplementation (beta-hydroxy beta-methylbutyrate \[HMB\] and vitamin D) + general physical activity recommendations * Enhanced nutritional supplementation (HMB and vitamin D) + supervised exercise program Enhanced nutritional supplementation consists of HMB combined with vitamin D (and calcium, when applicable), administered in addition to standard nutritional care.

The supervised physical activity program consists of structured, progressive resistance and functional exercises adapted to each participant's postoperative condition, targeting major muscle groups to improve muscle strength and functional capacity. Participants assigned to general physical activity receive standard recommendations according to routine clinical practice. Physical activity levels are objectively assessed using a wearable accelerometer.

Follow-up and Assessments: Approximately one month after surgery, once initial postoperative recovery has been achieved, participants enter the intervention and assessment phase (baseline visit) and are followed for approximately six months, with follow-up assessments at around 3 and 6 months. A comprehensive morphofunctional evaluation is performed at baseline and repeated at 6 months, including body composition, muscle strength, functional performance, and nutritional assessment using techniques such as bioelectrical impedance analysis, nutritional ultrasound, and standardized functional tests. Additional strength and resistance tests are also conducted as part of the study-specific evaluations. Biological samples (blood, urine, and stool) are collected at predefined time points to assess metabolic, inflammatory, and microbiota-related parameters. At the 3-month visit, a partial assessment is carried out, including selected clinical, functional, and questionnaire-based measures(including validated questionnaires assessing health status, quality of life, dietary intake, physical activity levels, and psychological well-being), allowing evaluation of both short- and medium-term changes during postoperative recovery. For participants assigned to the structured and supervised physical activity program, physical activity adherence, intensity, and patterns are objectively monitored using a wearable accelerometer, which is worn for 7 consecutive days monthly throughout the follow-up period, providing quantitative data on real-world physical activity behavior.

Study Relevance: By integrating perioperative nutritional care with structured postoperative interventions within a factorial design, the NIMA study aims to determine the independent and combined effects of nutritional supplementation and physical activity on recovery. The findings may contribute to optimizing perioperative care and improving functional outcomes in patients undergoing colon cancer surgery.

• Plasma concentration of inflammatory and metabolic biomarkers measured by multiplex immunoassay [Time frame: From baseline (first postoperative visit), 3 months and 6 months follow-up]
• Percentage of DNA methylation in peripheral blood mononuclear cells (PBMCs)by quantitative PCR [Time frame: Baseline (first postoperative visit) and 6 months follow-up]
• Change in urinary oxylipin concentrations by UHPLC-MS/MS [Time frame: Baseline (first postoperative visit) and 6 months follow-up]
• Change in relative abundance of gut microbiota taxa [Time frame: Baseline (first postoperative visit) and 6 months follow-up]
• Change in health-related quality of life score (EORTC QLQ-C30) [Time frame: Baseline (first postoperative visit), 3 months, and 6 months follow-up]