Clinical trial NCT01843608: Effect of Combined Exercise Post-treatment Intervention in Lean Mass Recovery in Breast Cancer Survival.
Official title: Effect of Combined Training Post-treatment Intervention in Lean Body Mass Recovery in Breast Cancer Survival. A Randomised Controlled Trial.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Sarcopenic Obesity in Breast Cancer Survival
Muscle Strength Quantitative Trait Locus 1
Cardiopulmonary Capacity
Quality of Life
Fatigue
Depression
Keywords: Physical treatment
Exercise prescription to breast cancer survival
Side cancer effect treatment
Lead sponsor: Universidad Politecnica de Madrid
Sponsor class: OTHER
First posted: 2013-04-30
Enrollment: 90
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Breast cancer survival it is affected by the side effects related to the illness, the treatments or even the behavioral factors (e.g. inadequate diet, sedentary behavior) that create in this women an important quantity of psychological and physical disorders. Prior systematic reviews and meta-analyses have demonstrate that supervised aerobic training is a safe, feasible, and effective adjunct therapy to improve a broad range of physiological and psychological outcomes in women with early breast cancer. However the vast majority of studies to date have focused on the efficacy of exercise to improve symptom control outcomes in breast cancer patients either during or following the completion of adjuvant therapy.

Most relevant consequences are found in women that have to undergo surgery as 16% to 43% of women with breast cancer suffer functional limitation in the shoulder, inflammation, pain or strength and flexibility reduction in upper body limbs one year after surgery with a high prevalence which is rising.

Weight gain is associated with decreased quality of life and increased risk for several comorbid conditions, such as cardiovascular disease and diabetes. The most of the cardiopulmonary problems are induced by chemotherapy or radiotherapy, because of the treatments effect in the heart and its consequences in cardiorespiratory fitness of these women.

These side effects become in important limitations to allow women return their normal life style. These limitations have a severe effect in decreasing of physical activity practice, which have visible consequences in increasing general fatigue and calcium deficiency in bones due to the age and some adjuvant treatments.

Previous studies found that patients with breast cancer who gained modest amounts of weight were significantly more likely to experience disease recurrence and die from breast cancer and other causes that those who were weight stable. In addition, two thirds of the studies that have assessed body composition change in relation to weight gain in this patient population observe no net gain in muscle mass or loss in muscle mass as body weight and adipose tissue increase. These changes are defined as sarcopenic obesity. This kind of obesity is characterized by weight gain in the presence of lean tissue loss or absence of lean tissue gain. In addition fat tissue gain is related with other health disorders such as diabetes, functional limitations and poor survival levels. Treatment for this unique pattern of weight gain is an exercise intervention, especially strength training.

Psychological effects have to be took account as cancer produce important aftermath. Large scientific evidence shows the psycho-emotional alterations in women diagnosed with breast cancer at some point in their life.

World Health Organization (WHO) defines quality of life as "individuals perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns. It is a broad ranging concept affected in a complex way by the person's physical health, psychological state, level of independence, social relationships, personal beliefs and their relationship to salient features of their environment." Following this definition numbered of researches have been developed, presenting interest in both physiological and psychological changes and improvements, as show different studies.

HYPOTHESIS The primary hypothesis of this study is that group exercise intervention, combining aerobic and strength training, will reduce lean mass and body fat tissue in breast cancer post treatment survival.

Secondary hypothesis of this clinical trial are follows:

1. Combined exercise intervention will increase maximal strength level of chest press and leg press.
2. Combined exercise intervention will increase maximal cardiopulmonary capacity, assessed by Peak Oxygen Consumption(VO2peak), which has been confirmed as an important value in survivals. In addition, ACSM propose this value as the Gold Standard to assess fitness level.
3. Combined exercise intervention will increase global Isometric Strength Index, assessed by Grip Strength Dynamometer.
4. Combined exercise intervention will improve range motion in upper-limbs.
5. Patients Reported Outcomes (PROs), such as quality of life (QoL), Health perception and depression.

Detailed description: This study will be a 3-month, two arms, randomized controlled exercise intervention trial, will be developed. After baseline measurements, participants will be randomized into the treatment and control groups by using a blocked randomization procedure.

This study will be developed through a collaboration between Technical University of Madrid (UPM) and Cancer Patients Spanish Group (GEPAC). This project will be carried out at the facilities of the Physical Activity and Sport Science (FCCAFD-INEF) and it was approved by the Ethical Committee of the UPM.

Women will be recruited from hospitals through posters and oncologist information and the diffusion of the project that GEPAC will do between their members. Women who present interest to be contacted will be phoned or mailed a study flyer and will be asked to fill in an initial questionnaire The intervention will be performed in a social framework. It will try to provide different skills to women, in order to improve self-trust and self-knowledge. Other important goal will be to give to women a space where they shared all their experiences and help women were going through the same situation.

The exercise program will be designed and conducted by qualified in Physical Activity and Sport Sciences. The exercise program will consist in a combined two days per week of supervised training program and one day per week of briskly walking by themselves, following a document, designed by the specialist trainer, which will be given at the beginning of the program. The intervention will have a duration of 12 consecutive weeks. The intensity will be increasing progressively from 65% to 85% of heart rate. The intensity will be controlled by heart rate monitor trademark POLAR FT7. Prescription intensity will be done using Karvonen equation, recommended method to work with risk population.

Every supervised session will have the same structure and will have a duration of 60 minutes. American College Sport Medicine (ACSM) Guidelines for Cancer Patients will be followed for the session design. Participants will be divided in groups of 15 per class to provide more individual attendance.

The first 10 minutes will be the warm up which will include joint mobilizations, different kinds of movements, briskly walking and running.

Next part will consist in aerobic exercise where the principal goal will be practice activities what will increase cardiopulmonary fitness and the functional capacity of the participants. Practiced activities will be "impact activities" which are the activities that weight is supported by the legs. They activate the bone regeneration and prevent osteoporosis. Interval training will be performed in this part, with 30 seconds of high intensity and 3 minutes of active recovery. Then, strength exercises with elastic band and activities where the women support the own weight will be developed to improve general strength and increase lean mass. The intensity will be quantified with the number of repetitions (from 8 to 15) and sets (from 2 to 3).

The last part will be stretching exercises dedicated to improve the joint mobility and the muscle flexibility of upper body limbs and the general muscles relax after training.

Women will be contacted 3 months after the project to know the real effect in adherence of the participant and in the global strength.

All adverse events that could occur during the intervention time will be register for the project coordinator contacting by phone with the patients.

These outcomes were assessed baseline and they were repeated after 12 weeks again.

Lean body mass and fat body mass Percentage of fat mass and percentage of muscle mas will be assessed by bio impedance, using TANITA BC-601F machine.

Demographics and clinical data Age, marital status, profession, quantity of physical activity before and after the disease, subtype of tumor, type of resection and type of endocrine medication will be recorded at baseline measurements.

Anthropometric assessments Weight, high, hip and waist circumferences and waist-hips ratio. Arm volumetries will be done to check that arm swelling did not increase.

Strength It will be assessed using two types of assessments. First type will be grip strength in hands, legs and back. Global strength will be assessed by Strength Index, which will be obtained adding all grip strength values and dividing de result by the participant weight. Grip Strength dynamomyter T.K.K.5401 to arms strength and T.K.K.5402 to legs and back strength will be used. Other studies will have used this method in order to obtain strength levels in breast cancer women demonstrating that is a feasible and safe method in this population. Second type of strength test will be 8 RM protocol to predict 1 Repetition Maximum (RM), following National Strength and Conditioning Association guidelines (NCSA 2008) and Mayhew formulae will be used to predict 1 RM. Test will be developed in PANATA machines.

Cardiovascular Capacity. It will be assessed by a submaximal cardiopulmonary exercise test following Prior to the start, women will have to complete the PAR-Q test to determine whether they are able to perform a graded exercise test.

Cardio-respiratory exercise responses will be assessed in each participant using a graded exercise test (GXT) on a treadmill. The test will be a modification of the Bruce GXT which was designed for use in clinical and older populations since the submaximal portion of the test can be done with walking and because it begins at a reduced intensity.

The ACSM guidelines to performance Cardio Pulmonary Exercise Test (CPET) will be followed to develop or to stop it, if it will be necessary.

Patient Report Outcomes

Quality of Life It is a very important outcome with a large definition related different concepts such as physical and psychological health, individual independence and social relationships. It was assessed by FACT-B questionnaire suggested in a review to be used in this population. The questionnaire presents 38 items and patients have to choose between 5 options (0 totally disagree and 4 totally agree) to describe their grade of accordance with the specific item

Depression Grade of depression was assessed by Center of Epidemiology Studies - Depression (CES.D). It was used in previous studies in order to determine the same outcome in breast cancer population. This test is a Likert scale, which presents 20 items. Patient has to identify how many times felt in that way during the previous week (from 0 never to 3 always). A score equal to 16 will be regarded as a mild depressive disorder

Health Survey Short Form -36 of Health Survey (SF-36) test will be used to assess Health Survey. Health status scores are abstractions, which obtain meaning through knowledge of how the scores are related to other variables and have been already used in cancer patients population. It presents 36 items and they are divided in 7 dimensions that will be interpreted together and separately.

Physical Activity Adherence and physical activity that women practice out of the program was collected by the validate questionnaire Godin Leisure-Time Test which registers times per week and intensity of the activities that women usually do in a typical week.

All statistical analyses will be done using SPSS Statistics 20.0 program. Confidential interval will be of 95% and the significance value will be 0.05 to determine the significance of the results.

Baseline characteristics of participants across the intervention and control groups were compared using Student t-test for continuous outcomes.

Between women comparisons of those randomized to treatment versus control for changes in FACT-B, FACT-F, SF-36 and CES-D, scores across months 0-3 will be made using Student t-test, after determining that adjustment for potential confounders do not alter the results.

Confounders examined included postmenopausal status, BMI status, baseline levels of sport and leisure-time physical activity.

Pearson correlation coefficients were used to evaluate associations between changes in body composition and strength and cardio-pulmonary status and changes in PROs scores. All probability values will be tested with the 2-tailed test.

Follow up 4 months after intervention will be compared with baseline and post intervention measures using ANOVA test.

Eligibility criteria: Inclusion Criteria:

* Breast cancer diagnosed confirmed stage I-IIIA.
* Randomized disposition.
* Minimum of forty-five days and maximum of thirty-six months after finishing treatments (chemotherapy and radiotherapy).
* 0-1 in Eastern Cooperative Oncology Group (ECOG) scale (present the ability to walk briskly)
* Oncologist approval.
* Informed Consent signed.
* Community of Madrid inhabitant.

Exclusion Criteria:

* Metastasis presence
* Serious medical risk such as unstable cardiac condition or severe pulmonary disease and anticoagulants treatments.
* Oncology or primary care approval who verified the medical risk exclusion criteria.
* ECOG \> 1
* Pregnant

Primary outcomes:
measure: Lean mass percentage
timeFrame: 3 months
measure: Maximal Strength
timeFrame: 3 months
Secondary outcomes:
measure: Fat body mass
timeFrame: 3 months
measure: Cardiovascular capacity
timeFrame: 3 months
measure: Quality of Life
timeFrame: 3 moths
measure: Fatigue
timeFrame: 3 months
measure: Health Perception
timeFrame: 3 months
measure: Depression
timeFrame: 3 months
measure: Leisure-time exercise
timeFrame: 3 months
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Physical Activity and Sport Science Faculty
Study officials:
affiliation: Universidad Politecnica de Madrid
name: Javier Sampedro, Professor
role: STUDY_DIRECTOR
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