Multidisciplinary Prehabilitation and Postoperative Rehabilitation in Patients Undergoing Resection of Colon Cancer

Study Overview
=================
Brief Summary
-----------------
ONCOFIT is a randomized clinical trial with a two-arm parallel design aimed at determining the influence of a multidisciplinary prehabilitation + postoperative program on post-surgery complications in patients undergoing resection of colon cancer. This intervention will include supervised physical exercise, dietary behavior change, and psychological support comparing its influence to the standard care.

Detailed Description
-----------------
Nowadays, colon cancer is one of the most common types of tumors worldwide being surgical resection the elective therapy for its curation. However, a surgery is a stressful procedure that may involve several postoperative complications. Risk factors for such undesirable events are closely related to lifestyle issues including decreased physical activity levels or dietary unhealthy habits. Recent studies have suggested that the implementation of multidisciplinary prehabilitation and postoperative interventions based on lifestyle habits may be a potential strategy for accelerate post-surgical recovery. To the best of our knowledge, the combined effect of a Prehabilitation + Postoperative Programs (PPP) on post-surgery complications and functional capacity of patients undergoing resection of colon cancer remains unclear. ONCOFIT is a randomized clinical trial with a two-arm parallel design aimed at determining the influence of a multidisciplinary PPP on post-surgery complications in patients undergoing resection of colon cancer. This intervention will include supervised physical exercise, dietary behavior change, and psychological support comparing its influence to the standard care. Primary and secondary endpoints will be assessed at baseline, at preoperative conditions, at the end of the PPP intervention and 1-year post-surgery, including: post-surgery complications, prolonged hospital length of stay, readmissions and emergency department call within 1-year after surgery, functional capacity, patient' reported outcome measures targeted, anthropometry and body composition, clinical markers, physical activity levels and sedentariness, dietary habits, others unhealthy habits, sleep quality and fecal microbiota diversity and composition. Considering the feasibility of the present intervention in a real-life scenario, ONCOFIT will contribute to the standardization of a cost-effective strategy for preventing and improving health-related consequences in patients undergoing resection of colon cancer with an important clinical and economic impact, not only in the scientific community but also in the clinical practice.

Official Title
-----------------
Multidisciplinary Prehabilitation and Postoperative Rehabilitation for Avoiding Complications in Patients Undergoing Resection of Colon Cancer: ONCOFIT Study

Conditions
-----------------
Colon Cancer, Postoperative Complications

Intervention / Treatment
-----------------
* Behavioral: Prehabilitation program (4 week before the surgery)
* Behavioral: Postoperative program (12 week after the surgery)
* Other: Usual Care


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients older than 40 years Diagnostic of nonmetastatic colon cancer (i.e., including right, transverse, left, sigmoid, subtotal, total, and hemicolectomy) Not participating in a nutritional/ dietary intervention Being physical inactive (i.e., not to be participating in any physical exercise program in the last 3 months, or performing less than 600 metabolic equivalents (METS)/week of moderate-vigorous physical activity). To be capable and willing to provide informed consent Not to suffer from any specific condition that may impede testing of the study hypothesis or make it unsafe to engage in the multidisciplinary intervention (i.e., determined by the research staff). Exclusion Criteria: Medical contraindication for being engaged in an exercise or dietary program. Additional surgery planned within the 3-month intervention History of another primary invasive cancer Planning to receive adjuvant chemotherapy To be pregnant To present any of the following cardiac conditions: (i) myocardial infarction or coronary revascularization procedure within prior 3 months, (ii) uncontrolled hypertension (i.e., systolic ≥180 mmHg or diastolic ≥100 mmHg), (iii) uncontrolled arrhythmias (iv) valvular disease clinically significant, (v) decompensated heart failure or (vi) to suffer from known aortic aneurysm.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Usual Care/Control Group<br>Usual care group will follow the usual institutional pre-surgery care.. | Other: Usual Care<br>* Usual care group will follow the usual institutional pre-surgery care: (i) medication management, (ii) assessment of the surgery-derived risks, (iii) smoking cessation and peri-operative blood management. A trained nutritionist will evaluate the nutritional status of all patients at the baseline providing oral protein/vitamin supplementation, when necessary. Patients allocated to the control group will receive basic expert' advice on lifestyle changes.<br>|
| Experimental: Prehabilitation + Postoperative Programs (PPP) Group<br>PPP group will include 3 complementary modules: (i) supervised physical exercise, (ii) dietary behavior change, and (iii) psychological support. | Behavioral: Prehabilitation program (4 week before the surgery)<br>* This intervention will include 3 complementary modules: (i) supervised physical exercise: aerobic and strength High Intensity Interval Training (HIIT), 3 times per week (ii) dietary behavior change: nutritional talk + an informative brochure + a video summary, a session per week and (iii) psychological support: psychoeducation, written and verbal emotional expression, promotion of coping strategies, progressive muscle relaxation training, problem-solving and social skills, and self-efficacy enhancing, among others. This psychological component will also include counseling regarding smoking and alcohol cessation and sleep hygiene.<br>Behavioral: Postoperative program (12 week after the surgery)<br>* This intervention will include 3 complementary modules: (i) supervised physical exercise: aerobic and strength High Intensity Interval Training (HIIT), 3 times per week (ii) dietary behavior change: nutritional talk + an informative brochure + a video summary, a session per week and (iii) psychological support: psychoeducation, written and verbal emotional expression, promotion of coping strategies, progressive muscle relaxation training, problem-solving and social skills, and self-efficacy enhancing, among others. This psychological component will also include counseling regarding smoking and alcohol cessation and sleep hygiene. NOTE: Both preoperative and postoperative programs will be administer to the participants assigned to the intervention group.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-surgery complications. | Post-surgery complications determined by the Comprehensive Complication Index (CCI). Minimum value: 0 // Maximum value: no upper limit. Higher scores mean a worse outcome. | 1-year post-surgery (i.e., week 57) | 
| Post-surgery complications. | Post-surgery complications determined by the Comprehensive Complication Index (CCI). Minimum value: 0 // Maximum value: no upper limit. Higher scores mean a worse outcome. | 12 weeks after surgery (i.e., week 17) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Additional surgery-derived events. | Electronic medical records will be used to register data regarding primary and total prolonged hospital length of stay. | 1-year post-surgery (i.e., week 57). | 
| Additional surgery-derived events. | Electronic medical records will be used to register data regarding readmissions. | 1-year post-surgery (i.e., week 57). | 
| Additional surgery-derived events. | Electronic medical records will be used to register data regarding emergency department appointments. | 1-year post-surgery (i.e., week 57). | 
| Cardiorespiratory fitness | Cardiorespiratory fitness measured by the 6-minute walking test (6MWT) distance, expresed in total m. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Muscular strength | Muscular strength assessed by handgrip strength. Handgrip strength will be determined using a digital hand dynamometer and expressed as total kg. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Health-related quality of life. | The 36-Item Short Form Health Survey questionnaire (SF-36). Minimum value: 0 // Maximum value: 100. Higher scores mean a better outcome. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Self-scored depression inventory | The Beck Depression Inventory-II questionnaire. Minimum value: 0 // Maximum value: 63. Higher scores mean a worse outcome. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Trait and state anxiety | The State-Trait Anxiety Inventory (STAI). Minimum value: 20 // Maximum value: 80. Higher scores mean a worse outcome. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Dispositional level of optimism | The Life Orientation Test-Revised. Minimum value: 0 // Maximum value: 24. Higher scores mean a better outcome. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Positive and negative affect | The Positive and Negative Affect Schedule (PANAS). Positive affect: Minimum value: 10 // Maximum value: 50. Higher scores mean a better outcome. Negative affect: Minimum value: 10 // Maximum value: 50. Higher scores mean a worse outcome. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Satisfaction With Life | The Satisfaction With Life Scale. Minimum value: 5 // Maximum value: 35. Higher scores mean a better outcome. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Perceived emotional intelligence | The Trait Meta-Mood Scale (TMMS-24) is a 24-item self-report instrument with three subscales measuring three key aspects of perceived emotional intelligence: Attention, Clarity and Repair. Each of these three subscales consists of eight items with a 5-point Likert response format (ranging from 1 to 5). Subscale total scores are obtained by summing responses to all items and thus range from 8 to 40, with higher scores indicating greater level of the characteristic assessed. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Weight | Weight measured with a scale (kg). | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Height | Height measured with a stadiometer (cm). | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Neck, waist and hip circumferences. | Neck, waist and hip circumferences will be assessed with an anthropometric tape measure (cm). | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Bone mineral density | Body composition assessment will be obtained through a full-body dual energy X-ray absorptiometry scanner. Bone mineral density in g/cm2. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Lean mass | Body composition assessment will be obtained through a full-body dual energy X-ray absorptiometry scanner. Lean mass in kg. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Fat mass | Body composition assessment will be obtained through a full-body dual energy X-ray absorptiometry scanner. Fat mass in kg. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Visceral adipose tissue | Body composition assessment will be obtained through a full-body dual energy X-ray absorptiometry scanner. Visceral adipose tissue in kg. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Glycemic profile | Blood samples will be drawn from patient' antecubital vein in a supine position during the morning after an overnight fasting to assess the glycemic profile. We will obtain plasma glucose (mg/dL) and insulin (mg/dL) levels. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Lipid profile | Blood samples will be drawn from patient' antecubital vein in a supine position during the morning after an overnight fasting to assess the lipid profile. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Hepatic transaminases | Blood samples will be drawn from patient' antecubital vein in a supine position during the morning after an overnight fasting to assess the hepatic transaminases levels. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Red cells | Blood samples will be drawn from patient' antecubital vein in a supine position during the morning after an overnight fasting to assess the red cells levels. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Immunological blood profiles | Blood samples will be drawn from patient' antecubital vein in a supine position during the morning after an overnight fasting to assess the immunological blood profiles. The following parameters will be obtained: Leukocytes (10*3 uL), Neutrophils (10*3 uL), Lymphocytes (10*3 uL), Monocytes (10*3 uL), Eosinophils (10*3 uL), Basophils (10*3 uL) and LUC cells (10*3 uL). | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Inflammatory factors | Blood samples will be drawn from patient' antecubital vein in a supine position during the morning after an overnight fasting to assess the inflammatory factors levels (PCR, leptin, adiponectin, resistin, IL 6, IL 10 and PAI 1; all of them expressed as pg/mL) | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Renal function parameters | Blood samples will be drawn from patient' antecubital vein in a supine position during the morning after an overnight fasting to assess the renal function parameters (creatinine and urea; both will be expressed in mg/dL) | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Tumour markers | Blood samples will be drawn from patient' antecubital vein in a supine position during the morning after an overnight fasting to assess the tumour markers levels (CA 19-9, CA 242, CA 72-4, TPA and TPS; all will be expressed as pg/mL)) | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Hormones | Blood samples will be drawn from patient' antecubital vein in a supine position during the morning after an overnight fasting to assess the hormones levels (T3, T4, testosterone, cortisol, estrogens and DHEAs; all will be expressed as pg/mL)) | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Blood pressure. | The investigators will also asses systolic and diastolic blood pressure in the right arm at rest. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| HOMA index. | The investigators will calculate the homeostatic model assessment of insulin resistance index (HOMA). HOMA index was calculated as follows: (fasting glucose(mg/dl) x fasting serum insulin (μU/mL))/405. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| FLI index. | The investigators will calculate the fatty liver index (FLI) as a validated surrogate marker of non-alcoholic fatty liver disease. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Cardiometabolic risk. | The investigators will calculate a cardiometabolic risk score based on the International Diabetes Federation (IDF) criteria. The cardiometabolic risk score is a continuous variable with a mean of 0 and a standard deviation of 1 by definition, with lower scores denoting a more favorable profile. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Physical activity and sedentariness. | The International Physical Activity Questionnaire (IPAQ) will be used to evaluate the current physical activity level of the participants. The survey validity and reliability studies have been conducted in Turkey by Ozturk. The survey consists of 27 questions and 5 parts. Minimum value = 0 min/day of physical activity // Maximum value = 1440 min/day of physical activity. Higher scores imply a more physically active pattern. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Dietary habits. | A food frequency questionnaire (FFQ) conducted by a trained nutritionist. Based on dietary data from the FFQ, the investigators will calculate the Mediterranean Diet Score. Minimum value: 0 // Maximum value: 14. Higher scores mean a better outcome. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Others unhealthy habits. | A seven-day self-reported tobacco and alcohol consumption logs will be used to determine smoking and alcohol intake registering total number of cigarettes and alcoholic units/day, time and situation in which both are consumed and cigarette type of alcoholic drink. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Nicotine dependence. | The Fagerström Test for Nicotine Dependence will be used to measure patients' nicotine dependence. Minimum value: 0 // Maximum value: 10. Higher scores mean a worse outcome. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Sleep quality. | Sleep quality will be determined by the Pittsburgh Sleep Quality Index (PSQI) scale. PSQI global score ranges from 0 to 21, with a score higher than 5 indicating poor sleep quality | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 
| Fecal microbiota analysis | A fecal sample (50-60 g) will be obtained and analyzed. | Baseline (week 0), at preoperative conditions (week 5), at the end of the PPP intervention (week 17) and 1-year post-surgery (week 57). | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Post-surgery complications, Multidisciplinary intervention, Exercise, Dietary behaviour, Psychological support