Synergic Effects of Physical Activity and Probiotic on Gut Immune System and Quality of Life of Breast Cancer Survivors.

Study Overview
=================
Brief Summary
-----------------
Physical exercise along with gut microbiota improvement -because of probiotic intake- can improve the quality of life and immune system in breast cancer survivors. This is achieved because exercise improves the muscle mass in cancer patients (often reduced by treatment and/or inactivity), together with the gut microbiota improvement, this stimulates the inmune system function, improving the quality of life of these patients.

Detailed Description
-----------------
The aim of this study is to determine the effects of physical exercise together with the supplementation of a probiotic on gut microbiota balance, the gut immune system and quality of life (intended as functional and muscular capacity, physical qualities and emotional state) in breast cancer survivors . A randomized controlled pilot study has been designed in three parallel groups. Breast cancer survivors will be randomly assigned to each of the 3 groups: a) probiotic supplementation + supervised combined physical exercise (PEF), b) probiotic supplementation and habitual sedentary lifestyle (P), and c) control group will follow their usual lifestyle and will receive a placebo (C). The exercise intervention will last 12 weeks. It will include three weekly sessions of programmed physical exercise of   60 min duration (combined training). The exercise program will be individualized and will follow the rules of the world reference institutions for aerobic training. Each session will be held in a qualified fitness center and it will be supervised and individualized for each subject by professional experts .The two supplemented groups will take 3 capsules (Lactobacillus rhamnosus, Lactobacillus paracasei, Lactobacillus acidophilus, Bifidobacterium bifidum) a day (at night before bedtime) for 12 weeks. The variables gut microbiota, fecal levels of immunoglobulin A, cardiorespiratory capacity, anthropometry variables, lifestyle, muscular capacity, quality of life, anxiety, depression and stress levels will be analized at the beginning (baseline dose) and after 12 weeks of intervention.

Official Title
-----------------
Physical Activity Along With a Probiotic for the Immune System and Quality of Life Improvement in Breast Cancer Survivor: A Randomised Controlled Pilot Study

Conditions
-----------------
Breast Cancer Females

Intervention / Treatment
-----------------
* Other: Physical Exercise and probiotic group
* Dietary Supplement: Probiotic group
* Dietary Supplement: Placebo group


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Breast Cancer Survivors <18 aged. No chemotherapy treatment or that at least three months have passed after the last chemotherapy treatment before the beginning of the study. Breast cancer status: I-IV status. ECOG scale: 0-1. Normal weight. Exclusion Criteria: Extreme Diet. Exercise practice (at least at the doses recommended by WHO) Presence of heart disease Uncontrolled blood hypertension: (>160/90 mmHg). Uncontrolled metabolic disease Infectious chronic disease Uncontrolled pain Pregnancy or breast feeding Gastrointestinal disease Alcoholism Any condition that contraindicates the exercise practice in survivors cancer (fractures risk, severe leukopenia , low platelet count) Antibiotics intake during the study.

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

Sexes Eligible for Study
-----------------
Female

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Physical Exercise and probiotic group<br>The subjects will receive 3 weekly sessions of combined exercise supervised by professionals in a specialized gym (60 minutes each one). The exercise will consist of a combination of aerobic and strength exercises involving the main muscle groups. They will take the probiotic supplementation at the established dose, 3 capsules/day before bedtime. Each probiotic capsule contains Lactobacillus rhamnosus, Lactobacillus paracasei, Lactobacillus acidophilus, Bifidobacterium bifidum. | Other: Physical Exercise and probiotic group<br>* The exercise intervention will last 12 weeks. It will include three weekly sessions of programmed physical exercise of   60 min duration (aerobic and strength combined training). The exercise sessions will be individualized and will follow the rules of the world reference institutions for aerobic training. Each session will be held in a authorized fitness center and it will be supervised and individualized for each subject by expert professionals.The probiotic will be taken (3 capsules/day) for 12 weeks. Each probiotic capsule contains Lactobacillus rhamnosus, Lactobacillus paracasei, Lactobacillus acidophilus, Bifidobacterium bifidum.<br>|
| Experimental: Probiotic group<br>Participants will follow their usual sedentary lifestyle (i.e to practice less than 3 days a week of physical exercise, as is specified in the inclusion criteria). They will take the probiotic supplementation at the established dose. Each probiotic capsule contains Lactobacillus rhamnosus, Lactobacillus paracasei, Lactobacillus acidophilus, Bifidobacterium bifidum | Dietary Supplement: Probiotic group<br>* Probiotic supplementation (3 capsules/day) will be taken before bedtime for 12 weeks.Each probiotic capsule contains Lactobacillus rhamnosus, Lactobacillus paracasei, Lactobacillus acidophilus, Bifidobacterium bifidum.<br>|
| Placebo Comparator: Placebo group<br>They will follow their sedentary lifestyle. Placebo probiotic will consist of a maltodextrin capsule. | Dietary Supplement: Placebo group<br>* Subjects will take 3 capsules/day of placebo capsules (maltodextrin) for 12 weeks<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Quality of life of breast cancer survivors | Breast cancer survivors quality of life will be analyzed with the quality of life questionnaire from The European Organization for Research and Treatment of Cancer EORTC QLQ BR-23 test (a specific module for breast cancer survivors) | Quality of life will be analyzed at the beginning (baseline dose) and after 12 weeks of intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Functional capacity | Dynamic fitness cardiorespiratory | Functional capacity and physical quality will be analyzed at the beginning (baseline dose) and after 12 weeks of exercise intervention | 
| Change in Body Composition | Body Mass Index | Functional capacity and physical quality will be analyzed at the beginning (baseline dose) and after 12 weeks of exercise intervention | 
| Change in Muscular Capacity | Pressure manual test will be determined | Muscular capacity will be analyzed at the beginning (baseline dose) and after 12 weeks of intervention. | 
| Change in Dietary habits | Food Frequency Questionnaire | Lifestyle will be analyzed at the beginning (baseline dose) and after 12 weeks of intervention | 
| Change in Physical activity level | Physical activity questionnaire (IPAQ) will be used | Lifestyle will be analyzed at the beginning (baseline dose) and after 12 weeks of intervention | 
| Change in Anxiety state | The State-Trait Anxiety Inventory (STAI) | Emotional state will be analyzed at the beginning (baseline dose) and after 12 weeks of intervention | 
| Change in Depression state | Depression inventory (IDER) | Emotional state will be analyzed at the beginning (baseline dose) and after 12 weeks of intervention | 
| Change Stress state | Stress coping questionnarie for oncology patients will be used | Emotional state will be analyzed at the beginning (baseline dose) and after 12 weeks of intervention | 
| Change in Gut Microbiota | Microbial diversity, bifidobacteria and lactobacillus percentage | Gut microbiota will be analyzed at the beginning (baseline dose) and after 12 weeks of intervention) | 
| Change in Immune system | Fecal immunoglobulin A levels | Immunoglobulin A levels will be analyzed at the beginning (baseline dose) and after 12 weeks of intervention | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Breast Cancer Survivor, Probiotic, Immune System, Physical Exercise, Quality of Life, Gut Microbiota