Dietary Supplement on the Intestinal Microbiota in Patients With Colon Cancer

Study Overview
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Brief Summary
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Effect of a dietary supplement with antioxidant and anti-inflamatory properties on the intestinal microbiota in patients with colon cancer. Ramdonized placebo controlled clinical trial. Teratrophic study

Detailed Description
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Introduction: The alteration in the microbiota plays a fundamental role in the promotion and progression of colon cancer due to various pathways such as inflammation and oxidative stress. The use of substances with anti-inflammatory and antioxidant effect could be useful for the treatment of this disease. Methodology: Prospective randomized clinical trial, with three parallel groups and double blind. Patients with stage II or III colon neoplasia who are going to receive post-surgical chemotherapy will be included. Patients will be randomized to one of the following groups: group 1 (25 patients): product with hydroxytyrosol extract; group 2 (25 patients): product with curcumin and selenium extract. Group 3 (25 patients): placebo. Before starting chemotherapy, stool and blood samples will be taken, and gastrointestinal symptoms, quality of life, symptoms of anxiety-depression and evaluation of nutritional status will be assessed. When starting chemotherapy, they will start with a daily intake of the assigned dietary supplement. At 3 months ± 2 weeks after starting chemotherapy (at least 2 weeks must have passed since the last chemotherapy of the fourth cycle), the same assessment will be made as in the initial visit, in addition to recording adherence to the intervention dietary supplement and new health problems that have appeared since the previous visit.

Official Title
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Effect of a Dietary Supplement With Antioxidant and Anti-inflammatory Properties on the Intestinal Microbiota in Patients With Colon Cancer. Randomized, Placebo-controlled Clinical Trial. TERATROPHO Study.

Conditions
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Colon Cancer

Intervention / Treatment
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* Dietary Supplement: Experimental Treatment, DCOOP Product, Hydroxytyrosol extract
* Dietary Supplement: Experimental Treatment,Indukern product, Curcumin and selenium extract
* Other: Control Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of stage II or III colo neoplasia Indication of adjuvant chemotherapy according to the Protocols for the diagnosis and treatment of cancer of the Intercenter Clinical Management Unit Sign the informed consent Exclusion Criteria: Systemic autoimmune diseases (systemic lupus erythematosus, antiphospholipid syndrome, Sjögren's syndrome, progressive systemic sclerosis -scleroderma-, idiopathic inflammatory myopathies -myositis-, vasculitis, Behçet's disease, relapsing polychondritis, etc.) Mellitus diabetes type 1 Previous gastrointestinal resections, except for appendectomy or surgery required to treat colon neoplasia Chronic intestinal pathologies (inflammatory bowel disease, celiac disease, lymphangiectasias) Continued consumption of probiotics, with the exception of dairy products or other natural fermented foods Chronic and continued use of NSAIDs or corticosteroids Allergy to any component of the product under investigation Pregnancy Mean consumption of > 3 UBE of alcohol per day Previous or concomitant neoplasia, unless curative treatment was received and ≥5 years have passed free of disease ECOG scale greater than or equal to 3 at the start of the clinical trial Grade 3-4 neuropathy that limits the use of oxaliplatin. History of familial adenomatous polyposis mediated by the APC gene or by Lynch syndrome (mutations MLH1, MSH2, PMS2, MSH6). Patients with partial or complete deficiency of the enzyme dihydropyrimidine dehydrogenase (DPD), which causes poor metabolism and the use of fluoropyrimidines is contraindicated.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomized in a 1:1 ratio
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 (25 patients)<br>A product of the company DCOOP, with hydroxytyrosol extract | Dietary Supplement: Experimental Treatment, DCOOP Product, Hydroxytyrosol extract<br>* Intervention group will receive a nutritional formula from DCOOP (Spain).<br>|
| Experimental: Group 2 (25 patients)<br>A product of the company Indukern, with extract of curcumin and selenium | Dietary Supplement: Experimental Treatment,Indukern product, Curcumin and selenium extract<br>* Intervention group will receive a nutritional formula from Indukern (Spain).<br>|
| Placebo Comparator: Group 3 (25 patients)<br>Placebo | Other: Control Treatment<br>* Control group will receive a placebo (product loading substance)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the alpha diversity index (Shannon) | This diversity index is a quantitative indicator of the number of different bacteria that are present in a stool sample, taking into account the uniformity in the distribution of these bacteria in these species. Diversity index value increases both when the number of species increases and when evenness increases. The Shannon index is a well-known diversity index used in microecological studies. The higher the Shannon index value, the higher the community diversity. It is calculated as: H = -Σpi * ln(pi), where H is the Shannon Diversity Index. Σ is a Greek symbol that means sum. ln is natural log. pi is the proportion of the entire community made up of species i. The minimum value the Shannon diversity index can take is 0. Such a number would tell us that there is no diversity - only one species is found in that habitat. There is no upper limit to the index. | From baseline to 3 months about 2 weeks after starting chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in weight | Weight in kg | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Change in height | Height in m | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| BMI (body mass index) changes | Measured by body composition analysis | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Mediterranean diet adherence questionnaire | to evaluate adherence to a Mediterranean diet pattern. It consists of 14 items in which different components of the Mediterranean diet are evaluated (number of pieces of fruit consumed per day, number of portions of legumes consumed per week...). Each item is scored as 0 or 1. A total score of <9 indicates poor adherence, while a score of ≥9 indicates good adherence. | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Maximum and mean value of 3 measurements in dominant hand dynamometry | Measured in kg | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Maximum and mean value of 3 measurements in non dominant hand dynamometrydynamometry | Measured in kg | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Mean dominant arm circumference | Measured in cm | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Calf circumference in the dominant leg | Measured in cm | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Anteroposterior diameter of the rectus femoris of the quadriceps in the dominant thigh | Measured in cm | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Transverse diameter of the rectus femoris of the quadriceps in the dominant thigh | Measured in cm | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Cross-sectional area of the rectus femoris quadriceps in the dominant thigh | Measured in in cm² | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Transverse perimeter of the quadriceps rectus muscle in the dominant thigh | Measured in cm | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Mean value of 3 measurements of the anteroposterior diameter of abdominal subcutaneous adipose tissue | Measured in cm | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Mean value of 3 measurements of the anteroposterior diameter of abdominal visceral adipose tissue | Measured in cm | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Fat mass in bioimpedanciometry | Measured in kg | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Lean mass in bioimpedanciometry | Measured in kg | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Extracellular water in bioimpedanciometry | Measured in kg | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Phase angle 50 kHz in bioimpedance measurement | Measured in º | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Total cell mass in bioimpedance measurement | Measured in kg | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Appendicular muscle mass in bioimpedanciometry | Measured in kg | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Percentage of weight lost in the last 6 months | Measured in %. | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Percentage of weight lost in the last 12 months | Measured in %. | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Hemoglobin in blood | Measured in g/dl | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Mean corpuscular volume in blood | Measured in in fL | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Leukocytes in blood | Measured in in x10^9/l | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Lymphocytes in blood | Measured in in x10^9/l | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Platelets in blood | Measured in in x10^9/l | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Creatinine in blood | Measured in in g/dl | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Glucose in blood | Measured in in mg/dl | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Sodium in blood | Measured in mEq/l | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Potassium in blood | Measured in mEq/l | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Chlorine in blood | Measured in mEq/l | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Calcium in blood | Measured in in mg/dl | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Phosphorus in blood | Measured in in mg/dl | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Magnesium in blood | Measured in in mg/dl | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Iron in blood | Measured in in mcg/dl | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Blood cholesterol | Measured in in mg/dl | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| HDL cholesterol in the blood | Measured in in mg/dl | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| LDL cholesterol in the blood | Measured in in mg/dl | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Blood triglycerides | Measured in in mg/dl | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| ALT in blood | Measured in U/L | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| GGT in blood | Measured in U/L | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Alkaline phosphatase in blood | Measured in U/L | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Bilirubin in blood | Measured in mg/dl | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Total protein in blood | Measured in g/dl | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Albumin in blood | Measured in g/dl | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Ferritin in blood | Measured in ng/ml | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| 25OH vitamin D in blood | Measured in ng/ml | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Prealbumin in blood | Measured in mg/dl | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| C-reactive protein in blood | Measured in mg/dl | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Normalized prothrombin time | Measured in in INR | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Degree in ECOG Performance Status Scale | This scale was developed by the Eastern Cooperative Oncology Group (ECOG), currently the ECOG-ACRIN Cancer Research Group. It was published in 1982. The scale describes the level of functioning of a patient in terms of her ability to take care of herself, perform daily physical activity and physical capacity (walk, work…). It was devised to use standard criteria between different centers to measure how the disease affects a patient's daily living abilities. The scale has a score from 0 to 5 in whole numbers. Lower score indicates better functional capacity. Score 0 refers to fully active patients, capable of carrying out all activities as before the onset of the disease. A score of 5 indicates the death of the patient. | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Assess the effect of supplementation on quality of life: EORTC QLQ-30 test. | The EORTC quality of life questionnaire (QLQ) is an integrated system to assess the quality of life of cancer patients participating in international clinical trials. The main questionnaire is the QLQ-C30. Version 3.0 is currently the standard version. The QLQ-C30 is made up of multiple-item and single-item scales. Five functionality scales, three symptom scales, a global health status/quality of life scale, and six individual items are included. Each of the multiple item scales includes a different set of items; no item appears on more than one scale. All single-item scales and measures range in score from 0 to 100. A high scale score represents a higher level of response. Thus, a high score for a functionality scale represents a high/healthy level of functionality, a high score for global health status/quality of life represents a high quality of life, but a high score for a scale or isolated items of symptoms represents a high level of symptoms/problems. | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Assess the effect of supplementation on quality of life: EORTC QLQ-CR29 test. | It is a supplemental questionnaire module to be used together with the QLQ-C30. The QLQ-CR29 incorporates 4 multi-item and 19 single-item scales. A variety of common symptoms and problems are assessed in colorectal cancer patients. The scoring approach is identical in principle to that of the scales or isolated items of functionality and symptoms of the QLQ-C30. All scales and single-item measures have a score range of 0 to 100. A high score on the functionality scale and the isolated items of functionality represents a high level of functionality, while a high score for the scales and isolated items represents a high level of functionality. of symptoms represents a high level of symptomatology or problems. | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Assess the effect of supplementation on symptoms of depression-anxiety | Hospital Anxiety and Depression Scale (HADS). Its objective is to detect depressive and anxious disorders in non-psychiatric hospital services, avoiding overlapping with symptoms due to physical illness, without taking into account the physical aspects that may accompany anxiety/depression, focusing only on emotional ones. It is a self-administered scale with 14 items divided into 2 subscales (anxiety and depression) whose maximum score is 21 points for each of them. Based on the score obtained, patients can be classified as normal (<7), doubtful (between 8 and 10) and potential clinical case (≥11). The score is referred to the last week. | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Assess gastrointestinal tolerance to supplementation and chemotherapy | Gastrointestinal symptoms questionnaire: an own questionnaire created for this study will be carried out in which the presence of nausea, vomiting, diarrhoea, constipation, acid reflux, early satiety, abdominal distension and abdominal pain will be evaluated. Each variable is evaluated on a scale with 4 possible responses: absent, mild, moderate, severe. | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Change in serum C-reactive protein | Measured in mg/l | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Change in serum Il-6 | Measured in pg/ml | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Change in serum TNF-alpha | Measured in pg/ml | From baseline to 3 months about 2 weeks after starting chemotherapy | 
| Change in stool calprotectin | Measured in mcg/g | From baseline to 3 months about 2 weeks after starting chemotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intestinal microbiota,, antioxidants, anti-inflammatories