Colorectal Cancer (Diagnosis), Malnutrition or Risk of Malnutrition
Conditions
Keywords
Colorectal Cancer, Nutrition Support, Health Education, Patient-Reported Outcomes, Nutritional Risk, Cancer Rehabilitation, Randomized Controlled Trial
Brief summary
This clinical study aims to evaluate whether short-term personalized nutritional support, when combined with structured health education, can improve nutritional status, quality of life, and clinical outcomes in patients who have undergone surgery for colorectal cancer (CRC). Colorectal cancer is one of the most common cancers worldwide, and many patients experience malnutrition and poor physical condition during treatment, which can negatively affect recovery and long-term survival. In this multicenter, randomized, controlled clinical trial, approximately 360 postoperative CRC patients will be enrolled and randomly assigned to one of four groups: (A) nutritional enhancement combined with health education, (B) health education alone, (C) nutritional enhancement alone, or (D) standard care (control group). Nutritional support will include individualized diet counseling and oral nutritional supplements tailored to each patient's needs. Health education will be delivered using an Internet Plus approach, including weekly educational videos and expert consultations focusing on nutrition, physical activity, and mental health. The primary objectives are to determine whether these interventions can improve patients' short-term nutritional status and quality of life. Secondary outcomes include the impact of interventions on long-term survival, treatment-related side effects, patient adherence to nutrition recommendations, and psychological well-being. This study will also investigate the biological mechanisms underlying the clinical effects by analyzing changes in the gut microbiome, blood-based metabolic profiles, and immune responses. Blood, stool, and tumor tissue samples will be collected and analyzed using advanced techniques, including untargeted metabolomics, metagenomics, and single-cell sequencing. This trial is designed to provide evidence for the integration of nutritional strategies into routine cancer care, and to guide the development of more personalized, effective nutrition-based therapies for colorectal cancer patients. Participants will be followed for up to annually up to 5 years to evaluate both clinical outcomes and biological markers of response.
Detailed description
This is a prospective, multicenter, open-label, randomized controlled clinical trial designed to assess the effects and underlying mechanisms of short-term nutritional enhancement combined with health education on clinical outcomes in patients undergoing surgery for non-metastatic colorectal cancer (stages IIa, IIb, IIIa). The rationale is based on the high prevalence of malnutrition among CRC patients, which significantly impacts treatment tolerance, quality of life, and long-term prognosis. Eligible participants will be randomized into four parallel arms: (1) individualized nutritional enhancement plus structured health education; (2) structured health education alone; (3) individualized nutritional enhancement alone; and (4) standard care without additional intervention. Personalized nutrition plans will be developed based on energy and protein needs, supported by dietary counseling and the provision of oral nutritional supplements. Health education will be delivered through a digital platform, featuring weekly videos and interactive content on nutrition, exercise, and psychological well-being. The study includes a 14-day intervention phase and a 12-month follow-up period. Outcomes will be assessed at baseline, and at 1, 2, 3, 6, and 12 months, and annually up to 5 years to evaluate both clinical outcomes and biological markers of response.post-intervention. Key endpoints include improvements in nutritional status, patient-reported quality of life, and overall survival metrics. To investigate mechanisms, the study incorporates biological sampling and multi-omics analysis. Non-targeted serum metabolomics, gut microbiota metagenomics, and single-cell RNA sequencing of tumor and adjacent normal tissues will be used to characterize metabolic and immune changes associated with the interventions. The study also evaluates the role of inflammatory markers and immune cell profiles in mediating clinical effects. This trial is expected to generate high-quality evidence supporting the integration of nutrition and health education strategies into standard postoperative care for CRC patients. It may also identify novel metabolic or microbial biomarkers associated with treatment response and prognosis, contributing to the development of precision nutrition approaches in oncology.
Interventions
DIETARY_SUPPLEMENTPersonalized Oral Nutritional Supplementation
Participants receive individualized oral nutritional supplementation based on energy and protein requirements, calculated using the Harris-Benedict equation and body weight (1.2-1.5 g protein/kg/day). The supplement may include complete nutrition powder, whey protein powder, and compound multivitamins. The intervention is prescribed and monitored by a clinical nutrition team and adjusted every 3 days during the 14-day intervention phase. The goal is to ensure both energy and protein intake targets are met. Supplements are administered in addition to standard meals.
DRUGPersonalized Parenteral Nutritional Supplementation
For participants unable to meet nutritional goals through oral intake, parenteral nutrition is administered intravenously. The formulation includes amino acids, glucose, lipids, electrolytes, trace elements, and vitamins. Dosages are aligned with those of the enteral nutrition group, ensuring a consistent intake of energy and protein (1.2-1.5 g/kg/day protein). Formulation and administration follow standardized hospital protocols and are supervised by the nutrition support team.
BEHAVIORALStructured Nutrition-Focused Health Education
Participants receive structured health education focused on nutrition, physical activity, and psychological well-being. The education is delivered over 14 days using a digital Internet Plus platform, featuring weekly videos, interactive Q&A sessions, and guidance from a multidisciplinary nutrition support team. Educational content covers dietary recommendations, exercise safety, stress management, and post-treatment recovery strategies. Materials are updated weekly, and participants may access them remotely via smartphone or tablet. This intervention aims to improve nutrition knowledge, adherence, and health behavior change.
Sponsors
Xiaoqin Luo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Masking description
Laboratory personnel conducting metabolomic, microbiome, and single-cell analyses will remain blinded to group allocation to reduce bias during data generation and interpretation.
Intervention model description
This is a prospective, multicenter, open-label, parallel-group randomized controlled trial involving four intervention arms. Participants are assigned in a 1:1:1:1 ratio to one of the following: (A) short-term nutritional enhancement combined with health education, (B) health education alone, (C) nutritional enhancement alone, or (D) standard care. Stratified randomization is performed based on baseline nutritional status and cancer stage to ensure group balance.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent * Age ≥ 18 years * Pathologically confirmed diagnosis of colon or rectal cancer * Mentally alert and capable of communication * Willing to participate in follow-up, with an estimated life expectancy of more than 6 months * Cancer stage IIa, IIb, or IIIa
Exclusion criteria
* Nutritional risk screening score of mPG-SGA \< 2 or NRS-2002 \< 3 * Diagnosed with AIDS * History of organ transplantation * Pregnant or breastfeeding women * Concurrent participation in another interventional clinical trial * Inability to care for oneself independently * Inability to engage in physical activity during the perioperative period * Severe comorbid conditions (e.g., uncontrolled cardiovascular disease, severe hepatic or renal dysfunction) * Known allergy or intolerance to components of the nutritional supplements used in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Global Health Status Score on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Assessment of patients' perceived overall health status using the global health subscale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Scores range from 0 to 100, with higher scores indicating better global quality of life. |
| Progression-Free Survival (PFS) in Cancer Patients | From date of enrollment until death or last follow-up (up to 5 years) | Progression-free survival is defined as the time from enrollment to the first documented disease progression or death from any cause, whichever occurs first. Patients without progression at the time of last follow-up will be censored. PFS will be analyzed using Kaplan-Meier estimates and Cox regression models, stratified by nutritional status. |
| Overall Survival (OS) in Cancer Patients | From date of enrollment until death or last follow-up (up to 5 years) | Overall survival is defined as the time from the date of enrollment to the date of death from any cause. Patients still alive at the last follow-up will be censored. Kaplan-Meier survival analysis and Cox proportional hazards regression will be used to estimate survival and explore associations with baseline and longitudinal nutritional status. |
| Change in Symptom Scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Assessment of symptom burden including fatigue, pain, nausea/vomiting, appetite loss, sleep disturbance, constipation, diarrhea, and financial difficulty using symptom subscales of the EORTC QLQ-C30. Each symptom is scored separately from 0 to 100, with higher scores indicating worse symptom severity. |
| Change in Nutritional Status Assessed by Modified Patient-Generated Subjective Global Assessment (mPG-SGA) | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Longitudinal assessment of nutritional status using the mPG-SGA, a validated tool composed of five sections (weight loss history, dietary intake, symptoms, function/activity, and age). Total scores range from 0 to ≥7 points, with higher scores indicating worse nutritional status. Patients will be classified as: 0-2 = Normal 3-6 = Mild malnutrition ≥7 = Moderate to severe malnutrition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Transferrin | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Serum transferrin concentration (g/L), a marker of protein status and iron metabolism. |
| C-Reactive Protein (CRP) | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Serum CRP (mg/L), a marker of systemic inflammation and acute-phase response. |
| Blood Glucose | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Fasting blood glucose (mmol/L), measured to assess metabolic function and risk of hyperglycemia. |
| Aspartate Aminotransferase (AST) | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | AST concentration (U/L), used as a liver function test and hepatotoxicity marker. |
| Alanine Aminotransferase (ALT) | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | ALT level (U/L), a liver enzyme measured to monitor hepatic injury. |
| Interleukin-1 (IL-1) | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | IL-1 concentration (pg/mL), a pro-inflammatory cytokine indicative of immune and inflammatory activity. |
| Tumor Necrosis Factor-alpha (TNF-α) | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Tumor Necrosis Factor-alpha (TNF-α) level (pg/mL) measured to assess systemic inflammation and cancer-related cachexia. |
| Serum Creatinine | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Serum creatinine (μmol/L), measured to evaluate kidney function and treatment-related nephrotoxicity. |
| Blood Urea Nitrogen | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Blood urea nitrogen (umol/L), used to monitor renal function and protein catabolism. |
| Total Bilirubin | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Blood urea nitrogen (umol/L), used to monitor renal function and protein catabolism. |
| Total Cholesterol | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Total cholesterol level (mmol/L), measured to assess lipid metabolism and nutritional status. |
| Triglycerides | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Serum triglyceride level (mmol/L), used to evaluate energy reserves and lipid metabolism. |
| High-Density Lipoprotein Cholesterol (HDL-C) | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | HDL-C (mmol/L), assessed as a marker of cardiovascular health and lipid status. |
| Low-Density Lipoprotein Cholesterol (LDL-C) | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | LDL-C (mmol/L), measured as a risk factor for cardiovascular disease and lipid status. |
| Interleukin-6 (IL-6) | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | IL-6 level (pg/mL), a pro-inflammatory cytokine measured to monitor systemic inflammation and cachexia. |
| Hemoglobin | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Hemoglobin concentration (\*10⁹/L), used to assess anemia and oxygen-carrying capacity. |
| White Blood Cell Count (Leukocytes) | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Total white blood cell count (\*10⁹/L), measured to monitor immune status and detect infection or myelosuppression. |
| Neutrophil Count | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Absolute neutrophil count (\*10⁹/L), used to assess infection risk and bone marrow suppression. |
| Lymphocyte Count | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Lymphocyte count (\*10⁹/L), measured to evaluate immune competence. |
| Red Blood Cell Count | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Red blood cell count (\*10¹²/L), used to assess erythropoiesis and anemia. |
| Platelet Count | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Platelet count (\*10⁹/L), measured to evaluate coagulation status and myelosuppression. |
| Height | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Standing height (cm) measured using a stadiometer with 0.5 cm precision. Values adjusted for presence of ascites, edema, or large tumors.ascites, systemic edema, and huge tumors. |
| Body Weight | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Body weight (kg) measured using a calibrated scale with 0.2 kg precision. Values adjusted if ascites or edema are present. |
| Body Mass Index (BMI) | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | BMI calculated as weight (kg) divided by height squared (m²), recorded to one decimal place. |
| Change in Anxiety Symptoms Assessed by Hospital Anxiety and Depression Scale (HADS-A) | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Assessment of anxiety using the HADS-A subscale of the Hospital Anxiety and Depression Scale. Scores range from 0 to 21, with higher scores indicating more severe anxiety symptoms. Results will be analyzed in relation to nutritional status (normal, mild, moderate malnutrition). |
| Change in Depression Symptoms Assessed by Hospital Anxiety and Depression Scale (HADS-D) | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Assessment of depressive symptoms using the HADS-D subscale of the Hospital Anxiety and Depression Scale. Scores range from 0 to 21, with higher scores indicating more severe depression. Results will be analyzed in relation to nutritional status (normal, mild, moderate malnutrition). |
| Functional Performance Measured by Karnofsky Performance Status (KPS) | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Functional performance will be evaluated using the Karnofsky Performance Status (KPS) scale, which ranges from 0 to 100. Higher scores indicate better functional ability and independence in daily activities. Longitudinal KPS changes will be assessed in relation to changes in nutritional status over time. |
| Changes in Sleep Quality Assessed by Pittsburgh Sleep Quality Index (PSQI) | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Sleep quality and disturbances will be evaluated using the Pittsburgh Sleep Quality Index (PSQI), a standardized questionnaire assessing seven components of sleep. Total scores range from 0 to 21, with higher scores indicating poorer sleep quality. PSQI scores will be analyzed in relation to nutritional risk categories and treatment phases. |
| Changes in Physical Activity Level During Cancer Treatment | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Assessment of leisure-time physical activity levels (mild, moderate, vigorous) and their relationship with nutritional status and cancer treatment response. |
| Changes in Nutrition-Related Knowledge, Attitudes, and Practices (KAP) | Baseline, after the intervention, 6 months after intervention; annually up to 5 years | Patients' dietary knowledge, attitudes, and practices will be assessed using a validated Nutrition KAP (Knowledge, Attitude, and Practice) questionnaire. The total score ranges from 0 to 104, with higher scores indicating better nutritional knowledge, more positive attitudes, and healthier dietary behaviors. Longitudinal changes in KAP scores will be evaluated in relation to treatment outcomes. |
| Healthcare Utilization and Cost of Nutrition-Related Care | From admission through 30-day post-discharge and annually for 5 years | Evaluation of healthcare utilization related to nutritional care, including total number of hospitalization days, number of ICU admissions, and direct costs associated with enteral and parenteral nutrition support. Metrics will be analyzed in relation to malnutrition risk at baseline and during treatment. |
| Incidence of Serious Adverse Events Related to Nutrition or Treatment | Continuously from enrollment through end of study follow-up (up to 5 years) | Tracking of serious adverse events potentially related to nutritional support or treatment, including infections, allergic reactions, gastrointestinal distress, and metabolic complications. |
| Change in Nutritional Risk Assessed by Nutritional Risk Screening 2002 (NRS-2002) | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Longitudinal evaluation of nutritional risk using the NRS-2002, which considers disease severity, nutritional impairment, and age. Total score ranges from 0 to ≥7 points. A score of ≥3 indicates nutritional risk and warrants intervention; \<3 indicates no immediate risk. |
| Serum Total Protein | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Serum total protein concentration (g/L), used to evaluate protein-energy nutritional status. Measured using standard biochemical assays. |
| Serum Albumin | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Serum albumin concentration (g/L), used to assess visceral protein status and systemic inflammation. |
| Serum Prealbumin | Baseline, after the intervention, 1, 2, 3, 6, and 12 months after intervention; annually up to 5 years | Serum prealbumin level (mg/L), an indicator of short-term changes in protein-energy nutritional status. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Predictive Value of Baseline Nutritional Indicators for 30-Day Clinical Events | Baseline to 30 days post-admission | Evaluation of whether baseline nutritional indicators-including mPG-SGA scores and laboratory biomarkers such as albumin, prealbumin, and CRP-predict 30-day clinical outcomes, including mortality, ICU admission, and significant unintentional weight loss (\>5%). Logistic regression will be used for model construction and discrimination. |
| Patient Adherence to Out-of-Hospital Nutritional Support | Baseline to 12 months post-treatment initiation | Evaluation of patient-reported adherence to prescribed oral nutritional supplements or enteral/parenteral support regimens after hospital discharge. Adherence data will be collected via structured interviews and compared with clinical outcomes and readmission rates. |
| Sociodemographic Determinants of Malnutrition | From baseline throughout study follow-up (up to 5 years) | Analysis of sociodemographic factors-including income level, education, employment status, and rural vs. urban residence-in predicting baseline malnutrition and nutritional deterioration over time. Multivariable models will be used to explore independent associations. |
| Agreement Between Nutritional Screening Tools (mPG-SGA vs. NRS-2002) | Baseline and each scheduled follow-up (up to 5 years) | Assessment of the diagnostic agreement, sensitivity, and specificity of two nutritional screening tools-modified Patient-Generated Subjective Global Assessment (mPG-SGA) and Nutritional Risk Screening 2002 (NRS-2002)-in detecting malnutrition risk. Agreement will be evaluated using Cohen's kappa and ROC curve analysis. |
| Nutritional Trajectory Typing and Clustering | From baseline to 12-month follow-up | Identification of distinct nutritional change trajectories over time using latent class growth analysis (LCGA) and hierarchical clustering based on serial measurements of mPG-SGA and anthropometric data. Trajectories will be used to classify patients into nutritional risk subgroups. |
Countries
China
Contacts
Primary ContactXiaoqin Luo, Ph.D
Backup ContactHexiang Yang, Ph.D
Outcome results
None listed