Creatine Supplementation and Resistance Training in Patients With Breast Cancer

Study Overview
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Brief Summary
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Background: Creatine supplementation is an effective ergogenic nutrient for athletes, as well as people for people starting a health or fitness program. Resistance training previously been identified as an important method of increasing muscle mass and strength among people, specially in people with cancer to avoid sarcopenia. The potential of creatine supplementation for adaptations produced by strength training in cancer patients are still unknown. Objective: the primary aim of this study is to evaluate the effectiveness of a 16-week supervised resistance training program intervention with and without creatine supplementation in patients with breast cancer. Methods: A multicentre, randomized, double-blind, placebo-controlled study designed to evaluate the effects of creatine supplementation in addition to resistance training in breast cancer patients. Patients will be randomly assigned to 3 groups: a control group (CG) and two experimental groups. The first resistance training group (RG) will perform resistance training, while the second resistance-creatine experimental group (RCG) will perform the same resistance training as the RG and will also receive a 5 g/day supplementation of creatine for the duration of the exercise the 16-week intervention. RG participants will follow the same daily dosing protocol, but in their case, with dextrose/maltodextrin. Resistance training will be a 16-week supervised workout that will consist of a series of resistance exercises (leg press, knee extension, knee bends, chest press, sit-ups, back extensions, pull-ups, and shoulder press) that involved the largest muscle groups of the body and will be performed three times a week on non-consecutive days. Both the RG and the RCG will receive a supplement of soluble protein powder (20-30 g) daily. Discussion: The results of this intervention will help to better understand the potential of non-pharmacological treatment for improving strength and wellbeing values in breast cancer patients with and without creatine supplementation.

Official Title
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Creatine Supplementation and Resistance Training in Patients With Breast Cancer (CaRTiC Study)

Conditions
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Breast Cancer, Supplementation, Resistance Training, Physical Performance, Quality of Life

Intervention / Treatment
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* Dietary Supplement: Creatine supplementation
* Other: Resistance training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage pTis-T1-T2-T3 pN0-1 M0 (early stage). Patients who have completed local treatment [surgery + radiotherapy (RT)] undergoing clinical follow-up in outpatient clinics with or without adjuvant hormone therapy treatment. Age: ≥18-60 years. ECOG Performance status from 0 to 1 (IK ≥80%). Body mass index above than 18.5. Without excessive alcohol consumption (men > 21 and women > 14 units/week). No current or previous illness or injury that may prevent participation and training. No recent systematic strength training. Not taking medications that are known to alter body composition (corticosteroids, metformin...). People who carry out some aerobic training will not be excluded (the activity carried out will be recorded weekly). Exclusion Criteria: Having received adjuvant or neoadjuvant chemotherapy. Metastatic carcinoma of the breast. Recurrence or second primary breast. History of previous cancer except previously treated basal cell carcinoma of the skin. Decompensated heart disease, uncontrolled hypertension (TAS>200 or TAD>110), heart failure (NYHA II or greater), heart failure or constrictive pericarditis, neutropenia, severe anemia (Hb<8.0 g/dl), blood count platelets <50,000 microL. Other health problems in which exercise is contraindicated Perform regular physical activity (150 min/week of moderate activity or 75 of vigorous activity), measured with the PVS questionnaire. Pregnancy. Criterion in the opinion of the investigator of inability to adequately understand the involvement and participation in this clinical study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control Group<br>They receive physical activity and nutrition recommendations. | |
| Experimental: Resistance training group<br>They will perform resistance training and placebo in the supplementation. | Other: Resistance training<br>* They will do resistance training. Resistance training will be a 16-week supervised workout that will consist of a series of resistance exercises (leg press, knee extension, knee bends, chest press, sit-ups, back extensions, pull-ups, and shoulder press) that involved the largest muscle groups of the body and will be performed three times a week on non-consecutive days.<br>|
| Experimental: Resistance training and creatine supplementation group<br>They will perform the same resistance training and will also receive creatine supplementation | Dietary Supplement: Creatine supplementation<br>* 5 g/day supplementation of creatine for the duration of the exercise the 16-week intervention. The RG and the RCG will receive a supplement of soluble protein powder (20-30 g) daily.<br>Other: Resistance training<br>* They will do resistance training. Resistance training will be a 16-week supervised workout that will consist of a series of resistance exercises (leg press, knee extension, knee bends, chest press, sit-ups, back extensions, pull-ups, and shoulder press) that involved the largest muscle groups of the body and will be performed three times a week on non-consecutive days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in maximal resistance (upper and lower body) | The maximal resistance in the upper and lower body will be measured in terms of the 5-repetition maximum test (5RM) (i.e. the maximum load that can be lifted five times) in chest and leg press exercises, respectively. Also a handgrip dynamometry test will be used to measure grip resistance. | 7 months follow up. Measures at 0, 2, 4 and 7 months. | 
| Genetic study | Saliva samples will be taken from the participants using buccal swabs (4N6FLOQSwab, Life Technologies, Carlsbad, CA). The genetic analysis will be performed using Biomark HD system microfluidic analysis technology (Fluidigm, South San Francisco, CA). From that analysis DNA will be extracted using the QIAmp DNA Mini kit (Qiagen, Hilden, Germany) and will be quantified fluorometrically using Qubit (LifeTechnologies). | Month 0 | 
| Change in Micro RNA (mRNA) | A 5/10 ml of urine will be collected in a 15 ml sterile plastic universal container tube kept at room temperature no more than 60 minutes, then stored at -20°C. Total RNA will be extracted from 400 μl of urine by using miRNeasy Serum/Plasma Kit (QIAGEN). | Month 0 and 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Physical function (walking) | Physical function is assessed by the 6 Minute Walk Test (6MWT) in a 20-meter corridor. Is a sub-maximal exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. | 7 months follow up. Measures at 0, 2, 4 and 7 months. | 
| Change in Physical function (sitting) | A 30-s chair test will be performed performed to measure functional capacity. The number of stands a person can complete in 30 seconds will be recorded. | 7 months follow up. Measures at 0, 2, 4 and 7 months. | 
| Change in Body composition | Body composition (percentages of type of tissue) will be measured using a bioelectrical impedance analysis (Inbody 770, In-Bldg). | 7 months follow up. Measures at 0, 2, 4 and 7 months. | 
| Change in dietary pattern | Habitual food consumption and nutrient intake will be evaluated using the dietary history questionnaire. | 7 months follow up. Measures at 0, 2, 4 and 7 months. | 
| Change in Gastrointestinal discomfort | The unidimensional Gastrointestinal Function questionnaire was used to assess gastrointestinal discomfort. This questionnaire consists of 9 items with a frequency scale of 4 response options [none (0 points), mild (1 point), moderate (2 points) and severe (3 points)]. | 7 months follow up. Measures at 0, 2, 4 and 7 months. | 
| Change in Quality of life (general) | The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) is used to assess general health-related quality of life status across physical functioning, physical role functioning, bodily pain, general health, vitality, social functioning, emotional role functioning, and mental health domains (higher scores indicating a greater quality of life). with scores for each of these scales (or dimensions) ranging from 0 to 100. Higher scores indicate higher quality of life. | 7 months follow up. Measures at 0, 2, 4 and 7 months. | 
| Change in Quality of life (cancer specific) | Cancer-specific quality of life is evaluated by the core quality of life (QLQ-C-30) questionnaire developed by the European Organization for Research and Treatment of Cancer (EORTC). This questionnaire includes five functional domains (physical, role, cognitive, emotional, and social, with higher scores representing greater function/quality of life) and three symptom scales (fatigue, pain, and nausea, with lower scores indicating greater quality of life/less symptom severity). | 7 months follow up. Measures at 0, 2, 4 and 7 months. | 
| Change in fatigue level | The cancer-related fatigue is assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale. For all FACIT scales and symptom indices, the higher the score the better the quality of life. | 7 months follow up. Measures at 0, 2, 4 and 7 months. |