Neoplasms

Digestive System Diseases

All Conditions

Colonic Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Herbal and Botanical

All Drugs and Chemicals

Cola

Optional

In pre-training:

Biopsy performed during the digestive surgery procedure

Final evaluation (minimum 1 day and maximum 7 days after the last training session): biopsy performed in the digestive surgery department.

Muscle biopsies

3 sessions per week for 18 weeks. Duration: 1 hour Training on different strength training machines for the main muscle groups of the lower and upper limbs. The training load will be gradually increased over the sessions.

Muscle Strengthening

fasting blood sample taken at assessments 1, 2, 3 and 4 for patients and assessment 1 for controls

Blood and urine samples

3 sessions per week for 18 weeks. Duration: 1 hour Training on a "classic" pedal bicycle (called an ergocycle). The intensity and duration of the training will be gradually increased over the sessions and according to the patient's abilities.

Aerobic Training

Carried out at least 15 days before surgery

1. st visit:

   * Nutritional assessment
   * Body composition
   * Psychometric tests of quality of life + IPAQ Test
   * VO2pic
2. nd visit:

   * Neuromuscular tests
   * Functional tests

Evaluation 1 pre-surgery

1. st visit:

   * Body composition
   * Nutritional assessment
   * Psychometric tests of quality of life
2. nd visit:

   * neuromuscular tests
   * Functional tests
   * Familiarization with training equipment if patient participates in re-training

Evaluation 2 post-surgery

performed 9 weeks after the beginning of training Identical tests to evaluation 1 + TM6

Intermediate Evaluation 3

Final post-training evaluation 4

Anaïs GOUTERON

Vanessa COTTET

Colon cancer is a real public health problem with more than 46,000 new cases diagnosed per year in France and about 650 cases in Burgundy. Muscle deconditioning (MD), which is characterized by a loss of muscle mass and function, is a frequent consequence in cancer patients and conditions the prognosis. Therefore, it is essential to understand its complex etiology in oncology in order to address the real need for therapeutic countermeasures in clinical practice. DM is a multifactorial process that is exacerbated by therapies. It induces neurogenic and muscular alterations that can profoundly affect patients' quality of life.

Currently, analyses of this phenomenon in oncology have been limited essentially to a global evaluation of physical performance, neglecting the muscular and nervous nature of the adaptations responsible for it.

Most studies analyzing the therapeutic effects of physical activity (PA) have shown numerous physiological and psychological benefits of aerobic exercise. However, this form of PA is still not very effective in preserving muscle mass.

Only muscle strengthening can have an anabolic effect by accelerating the rate of protein synthesis.

Neuromuscular Deconditioning and Reconditioning in Colon Cancer Patients: an APA Muscle Rendorcement Program

Neuromuscular Deconditioning and Reconditioning in Colon Cancer Patients: A Pilot Study of an APA Muscle Rendorcement Program

Tolerance in terms of level of effort and pain will be tested at each session and will condition the continuation or not of the sessions and therefore acceptability

Centre Hospitalier Universitaire Dijon

Skin and Connective Tissue Diseases

Rare Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Oculocerebral Syndrome With Hypopigmentation

Participants will perform a combination of strength and endurance training with low-to moderate-intensity during (neo-) adjuvant treatment with chemotherapy, approximately 6 months. All strength training will be supervised while the endurance training is home-based and followed up by a coach.

Participants will perform a combination of strength and endurance training with high intensity during (neo-) adjuvant treatment with chemotherapy, approximately 6 months. All strength training will be supervised while the endurance training is home-based and followed up by a coach.

Combination of strength and endurance training with low- to moderate intensity during chemotherapy

Low- to moderate intensity strength and endurance training

Combination of strength and endurance training with high intensity during chemotherapy

High intensity strength and endurance training

Truls Raastad, Professor

(Neo-)adjuvant chemotherapy for breast cancer has deleterious effects on muscle tissue resulting in reduced skeletal muscle mass, muscle function, and cardiorespiratory fitness. Various exercise regimens during cancer treatment have been shown to counteract some of these side effects. However, no study has compared the effect of high intensity training vs. low-to moderate intensity training on muscle tissue cellular outcomes and function in breast cancer patients during chemotherapy. The present study aims to compare the effects of high vs. low-to moderate intensity training on its ability to counteract deleterious effects of chemotherapy on skeletal muscle in women diagnosed with breast cancer. Eighty newly diagnosed women with breast cancer planned to start (neo-)adjuvant chemotherapy will be randomized to either a group performing a combination of strength and endurance training with high intensity or a group performing training with low to moderate intensity. Muscle biopsies from m. vastus lateralis for assessment of muscular cellular outcomes will be collected and muscle function and cardiorespiratory fitness will be measured before the first cycle of chemotherapy (or, when not possible, one week after) (T0), halfway through chemotherapy (T1), and after completion of chemotherapy (T2). It is estimated that approximately 50% will be willing to take muscle biopsies. The study will give important information about the effects of different training intensities for breast cancer patients during treatment and will contribute with knowledge about how to refine exercise programs that are effective and compatible with multidisciplinary management of breast cancer.

The aim of this study is to investigate the effects high and low-to-moderate exercise intensity on muscle cellular outcomes, muscle function, and cardiorespiratory fitness in breast cancer patients undergoing (neo-)adjuvant chemotherapy. We further aim to investigate if treatment including taxane treatment have larger negative effect on muscle than taxane-free treatment.

Our hypotheses are:

* Both high-intensity and low to moderate intensity strength and endurance training during (neo-)adjuvant chemotherapy will reduce negative treatment effects on muscle fiber size, mitochondrial function, cellular stress, and thus reduce the negative effect on cardiorespiratory fitness and muscle function. High-intensity training will be superior to low to moderate-intensity training in counteracting the negative treatments effects.
* Both high-intensity and low to moderate intensity strength and endurance training during (neo-)adjuvant chemotherapy will increase muscle and blood levels of potential anti-tumor myokines.
* Treatment including taxane administration will have larger negative effect on muscle fiber size, mitochondrial function, cellular stress, and thus cardiorespiratory fitness and muscle function than taxane free treatment regardless of training intensity.

This study is a two-group randomized controlled trial. The participants will be randomly allocated into two training groups; one group performing the combination of strength and endurance training with high intensity and the other group performing the training with low to moderate intensity during (neo-) adjuvant treatment for breast cancer. Power calculations indicate that 20 participants are sufficient in each group for our primary outcome muscle fiber cross-sectional area. As we estimate that approximately 50% of the participants will be willing to take muscle biopsies a total of 80 participants will be recruited leading to a total of 40 participants with muscle biopsies.

Before the training period (T0) muscle biopsies, questionnaires and blood samples will be taken before the first chemotherapy cure. The first 2-4 weeks after cure 1 will be used as a familiarization period for tests and exercises, and to complete the remaining T0 tests. Testing will include measurements of physical capacity, body composition, and physical activity levels. All measurements are repeated halfway into the treatment (T1) and after the completion of treatment (T2). Training will start between cures 2 and 3 and will last throughout the treatment period, approximately 6 months.

The strength training consists of two supervised sessions per week and includes the following exercises: seated leg-press, chest-press, seated leg-curl, seated-row, leg-extension, and standing overhead-press using dumbbells. The low-to-moderate intensity group will perform 12 repetitions for 3 sets at 50% of 6RM load in the first weekly session and 20 repetitions for 3 sets at 50% of 10RM load in the second weekly session. The high intensity group will perform 6 repetitions for 3 sets at 6RM load in the first weekly session and 10 repetitions for 3 sets at 10RM load in the second weekly session.

The endurance exercise is home-based and followed up by a coach. The low-to-moderate intensity group do continuous-based exercise (running, cycling, walking uphill or any other endurance-based activity) in bouts of at least 10 min at an exercise intensity of 40-50% of the heart rate reserve. The exercise frequency is recommended to be 2-4 times a week with the main aim to reach 150 min of moderate intensity endurance exercise per week. The high intensity group conduct high-intensity interval exercise. The sessions will consist of two-minute exercise intervals (running, cycling, walking uphill or any other endurance-based activity) at an exercise intensity of 80-90% of the heart rate reserve (at the end of the 3rd session) with two minutes of rest between intervals. During the first week after familiarization, each session will consist of 6 intervals. Thereafter, one bout will be added every fourth week until 10 bouts per session are reached as the maximum, corresponding to 75 min of high intensity per week.

The person performing all analyses on muscle tissue (primary outcome) is masked for intervention applied to the individuals and timepoint. The person doing the physical test is not masked.

Effects of Moderate and High-intensity Exercise During Chemotherapy on Muscle Cells in Women With Breast Cancer

Effects of Moderate and High-Intensity Exercise During (Neo-)Adjuvant Chemotherapy on Muscle Cellular Outcomes in Women With Breast Cancer: a Randomized Controlled Trial

Change from baseline (T0) to the 3 months time point (T1) and from baseline to the 6 months time point (T2) in blood lipids. This will be assessed in blood serum and plasma using ELISA methods.

Change from baseline (T0) to the 3 months time point (T1) and from baseline to the 6 months time point (T2) in C-reactive protein. This will be assessed in blood serum and plasma using ELISA methods.

Change from baseline (T0) to the 3 months time point (T1) and from baseline to the 6 months time point (T2) in creatine kinase. This will be assessed in blood serum and plasma using ELISA methods.

Change from baseline (T0) to the 3 months time point (T1) and from baseline to the 6 months time point (T2) in blood glucose. This will be assessed in blood serum and plasma using ELISA methods.

Change from baseline (T0) to the 3 months time point (T1) and from baseline to the 6 months time point (T2) in cortisol. This will be assessed in blood serum and plasma using ELISA methods.

Change from baseline (T0) to the 3 months time point (T1) and from baseline to the 6 months time point (T2) in hemoglobin. This will be assessed in whole blood using standard clinical measures.

Change from baseline (T0) to the 3 months time point (T1) and from baseline to the 6 months time point (T2) in physical activity. This will be assessed by the SenseWear Armband activity monitoring device. A SenseWear Armband is worn for 7 consecutive days each time point.

Change from baseline (T0) to the 3 months time point (T1) and from baseline to the 6 months time point (T2) in fatigue. This will be assessed using the Multi Dimensional Fatigue Inventory (MFI).

Change from baseline (T0) to the 3 months time point (T1) and from baseline to the 6 months time point (T2) in quality of life. This will be assessed using The European Organization for Research and Treatment of Cancer (EORTC)EORTC-QLQ30.

Change from baseline (T0) to end of intervention (end of training and treatment), approximately 6 months (T2) in muscle fiber cross-sectional area. This will be assessed by immunohistochemical staining of muscle fiber cross-sections for type 1 and type 2 muscle fibers and dystrophin (cell border).

Change from baseline (T0) to halfway into the intervention (halfway into training and treatment), approximately 3 months (T1) in muscle fiber cross-sectional area. This will be assessed by immunohistochemical staining of muscle fiber cross-sections for type 1 and type 2 muscle fibers and dystrophin (cell border).

Change from baseline (T0) to the 3 months time point (T1) and from baseline to the 6 months time point (T2) in satellite cell content in muscle fiber cross-sections. This will be assessed through immunohistochemical staining of satellite cells in muscle fiber cross-sections for type 1 and type 2 muscle fibers separately.

Change from baseline (T0) to the 3 months time point (T1) and from baseline to the 6 months time point (T2) in myonuclei content in muscle fiber cross-sections. This will be assessed through immunohistochemical staining of myonuclei in muscle fiber cross-sections for type 1 and type 2 muscle fibers separately.

Change from baseline (T0) to the 3 months time point (T1) and from baseline to the 6 months time point (T2) in protein levels of regulators of muscle fiber size (proteins involved in muscle protein synthesis and protein degradation \[e.i. mTOR, MuRF, S6K1, p70S6k\]). This will be assessed in muscle homogenate using Western blot analysis.

Change from baseline (T0) to the 3 months time point (T1) and from baseline to the 6 months time point (T2) in protein levels of regulators of muscle fiber cellular stress (Heat Shock proteins: Hsp 27, αB-crystalline, Hsp 60 and Hsp 70). This will be assessed in muscle homogenate using Western blot analysis.

Change from baseline (T0) to the 3 months time point (T1) and from baseline to the 6 months time point (T2) in protein levels of regulators of mitochondrial function (Citric syntase, Cox 4 and HADH). This will be assessed in muscle homogenate using Western blot analysis.

Change from baseline (T0) to the 3 months time point (T1) and from baseline to the 6 months time point (T2) in myokines with potential anti-tumor effects. This will be assessed in muscle homogenate using Western blot analysis.

Change from baseline (T0) to the 3 months time point (T1) and from baseline to the 6 months time point (T2) in maximal upper- and lower extremity muscle strength. This will be assessed as one repetition maximum in seated chest-press, seated single-leg press and knee extension.

Change from baseline (T0) to the 3 months time point (T1) and from baseline to the 6 months time point (T2) in cardiorespiratory fitness. This will be assessed as maximal oxygen uptake during maximal walking/running until exhaustion on a treadmill.

Change from baseline (T0) to the 3 months time point (T1) and from baseline to the 6 months time point (T2) in muscular endurance. This will be assessed as the number of repetitions on 30% of one-repetition maximum in knee extension.

Change from baseline (T0) to the 3 months time point (T1) and from baseline to the 6 months time point (T2) in fat free mass. This will be asses by dual dual energy X ray absorptiometry.

Change from baseline (T0) to the 3 months time point (T1) and from baseline to the 6 months time point (T2) in fat mass. This will be asses by dual dual energy X ray absorptiometry.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neuromuscular Deconditioning and Reconditioning in Colon Cancer Patients: an APA Muscle Rendorcement Program	NCT05099211	Colon Cancer Muscle Strength...	Muscle biopsies Muscle Strength... Blood and urine... Aerobic Trainin... Evaluation 1 pr... Evaluation 2 po... Intermediate Ev... Final post-trai...	18 Years - 80 Years	Centre Hospitalier Universitaire Dijon
Effects of Moderate and High-intensity Exercise During Chemotherapy on Muscle Cells in Women With Breast Cancer	NCT05218876	Breast Cancer F...	Low- to moderat... High intensity ...	18 Years -	Norwegian School of Sport Sciences
Neuromuscular Deconditioning and Reconditioning in Colon Cancer Patients: an APA Muscle Rendorcement Program	NCT05099211	Colon Cancer Muscle Strength...	Muscle biopsies Muscle Strength... Blood and urine... Aerobic Trainin... Evaluation 1 pr... Evaluation 2 po... Intermediate Ev... Final post-trai...	18 Years - 80 Years	Centre Hospitalier Universitaire Dijon

Spots Global Cancer Trial Database for muscle biopsies