Clinical trial NCT04586517: Effect of Heavy-load Resistance Training During Chemotherapy on Muscle Cellular Outcomes
Official title: Effects of Heavy-load Resistance Training During (Neo-)Adjuvant Chemotherapy on Muscle Cellular Outcomes in Women With Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Breast Cancer Female
Keywords: Breast cancer
Resistance training
Chemotherapy
Randomized controlled trial
Muscle biopsies
Cross-sectional fiber area
Lead sponsor: Uppsala University
Sponsor class: OTHER
Collaborators: name: Swedish Cancer Society
name: Norwegian Cancer Society
name: Norwegian School of Sport Sciences
name: University of Agder
name: Rigshospitalet, Denmark
name: Uppsala University Hospital
First posted: 2020-10-14
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel assignment
Primary purpose: TREATMENT

Brief summary: (Neo-)adjuvant chemotherapy for breast cancer is known to have a negative impact on muscle tissue resulting in reduced aerobic fitness, skeletal muscle mass and strength. Physical exercise during treatment may counteract some of these negative effects. However, the effects of resistance training alone have never been explored. The present study aims to investigate if heavy-load resistance training during (neo-)adjuvant chemotherapy counteracts negative effects on skeletal muscle in women diagnosed with breast cancer. The hypothesis is that (neo-)adjuvant treatment with chemotherapy will reduce muscle fiber size, impair mitochondrial function and increase indicators of cellular stress and that resistance training during treatment will counteract these negative effects. Fifty women recently diagnosed with breast cancer scheduled to start (neo-)adjuvant chemotherapy will be randomized to either an intervention group or a control group. The intervention group will perform supervised heavy-load resistance training twice a week over the course of chemotherapy (approximately 16-weeks) whereas the control group will be encouraged to continue with their usual activities. To increase interest in participation, controls will be invited to a 2-week introduction to the same resistance-training program as the intervention group following completion of chemotherapy. Muscle biopsies from m. vastus lateralis will be collected before the first cycle of chemotherapy, after chemotherapy, and 6 months later (6-month follow-up) for assessment of muscle cellular outcomes. Results from this intervention will provide further knowledge on how chemotherapy affects muscle tissue and how resistance training may counteract immediate and long-term treatment side effects. Results from this intervention will also contribute with knowledge about how to improve exercise programs that are effective for women undergoing chemotherapy against breast cancer.

Detailed description: The aim of this study is to investigate the effects of heavy-load resistance training on muscle cellular outcomes in women with breast cancer undergoing (neo-)adjuvant chemotherapy.

More specifically, the investigators' objectives are to

1. Investigate the effects of a heavy-load resistance training intervention on skeletal muscle fiber cross-sectional area.
2. Investigate the effects of a heavy-load resistance training intervention on regulators of muscle fiber size, muscle fiber function, cellular stress and mitochondrial function.
3. Investigate the effects of chemotherapy on skeletal muscle fiber cross-sectional area, regulators of muscle fiber size, muscle fiber function, cellular stress and mitochondrial function.
4. Explore the effects of heavy-load resistance training on the expression levels of myokines.

This study is a two-armed randomized controlled trial with follow-up at six months. With this design, the investigators can study the main effect and interactions between factors (groups). Participants will be randomized to either an intervention group or a control group.

Participants recently diagnosed with breast cancer will be recruited from Uppsala University Hospital. Based on power calculations, 50 participants will be included. Data will be collected before the first cycle of chemotherapy, after chemotherapy, and 6 months later (6-month follow-up.

Participants in the intervention group will perform supervised heavy-load resistance training twice a week from the week following the start of chemotherapy and throughout the course of treatment, approximately 16 weeks. Sessions will be performed at a public gym and led by trained coaches. The following six exercises will be included in the program: seated leg-press, seated chest press, seated leg-curl, seated row and seated leg-extension performed in machines and seated overhead-press using dumbbells. The first two weeks of the program represent familiarization to the training protocol and 1 RM (Repetition Maximum) tests. During this period, the participants will perform exercises at a light load. After the first 1 RM-test, training will progress in sets and training load before testing of 6- and 10 RM which will provide the participants with individualized loads. Rest periods between sets will be two (6 RM training load) and one minute (10 RM training load) for the two different sessions, respectively. The training load will be adjusted throughout the intervention period. Participants in the control group are encouraged to continue with their activity as usual i.e. maintain their habitual physical activity level and not initiate resistance training during chemotherapy. To increase interest in participation, controls will be invited to a 2-week introduction to the same resistance-training program as the intervention group following completion of chemotherapy and offered a 12-month membership at a local gym, free of charge.

Eligibility criteria: Inclusion Criteria:

* women diagnosed with stage I-III breast cancer
* literate in Swedish
* scheduled to undergo (neo-)adjuvant chemotherapy with a combination of taxanes and anthracyclines or only one of these treatments

Exclusion Criteria:

* unable to perform basic activities of daily living
* cognitive disorders or severe emotional instability
* other disabling comorbidities that might hamper physical training (e.g. severe heart failure, chronic obstructive pulmonary disease, orthopedic conditions, and neurological disorders)

Primary outcomes:
measure: Assessment of changes in muscle fiber cross-sectional area
timeFrame: From baseline to the 16 week time-point
Secondary outcomes:
measure: Assessment of changes in muscle fiber cross-sectional area
timeFrame: From baseline to 6-month follow-up
measure: Assessment of changes in satellite cell content in muscle fiber cross-sections
timeFrame: From baseline to the 16 week time-point and from baseline to 6-month follow-up
measure: Assessment of changes in myonuclei content in muscle fiber cross-sections
timeFrame: From baseline to the 16 week time-point and from baseline to 6-month follow-up
measure: Assessment of protein levels of regulators of muscle fiber size (proteins involved in muscle protein synthesis and protein degradation (e.i. mTOR, MuRF, S6K1, p70S6k)
timeFrame: From baseline to the 16 week time-point and from baseline to 6-month follow-up
measure: Assessment of changes in protein levels of regulators of muscle fiber cellular stress (Heat Shock proteins: Hsp 27, αB-crystalline, Hsp 60 and Hsp 70)
timeFrame: From baseline to the 16 week time-point and from baseline to the 6-month follow-up
measure: Assessment of changes in protein levels of regulators of mitochondrial function (Citric syntase, Cox 4 and HAD)
timeFrame: From baseline to the 16 week time-point and from baseline to the 6-month follow-up
measure: Assessment of changes in myokines with potential anti-tumor effects
timeFrame: From baseline to the 16 week time-point and from baseline to the 6-month follow-up
measure: Changes in muscle strength
timeFrame: From baseline to the 16 week time-point and from baseline to the 6-month follow-up
measure: Cardiorespiratory fitness
timeFrame: From baseline to the 16 week time-point and from baseline to the 6-month follow-up
Other outcomes:
measure: Assessment of changes fat free mass
timeFrame: From baseline to the 16 week time-point and from baseline to the 6-month follow-up
measure: Assessment of changes in fat mass
timeFrame: From baseline to the 16 week time-point and from baseline to the 6-month follow-up
measure: Assessment of blood lipids
timeFrame: From baseline to the 16 week time-point and from baseline to the 6-month follow-up
measure: Assessment of C-reactive protein
timeFrame: From baseline to the 16 week time-point and from baseline to the 6-month follow-up
measure: Assessment of creatine kinase-myocardial band
timeFrame: From baseline to the 16 week time-point and from baseline to the 6-month follow-up
measure: Assessment of blood glucose
timeFrame: From baseline to the 16 week time-point and from baseline to the 6-month follow-up
measure: Assessment of serum cortisol
timeFrame: From baseline to the 16 week time-point and from baseline to the 6-month follow-up
measure: Assessment of hemoglobin
timeFrame: From baseline to the 16 week time-point and from baseline to the 6-month follow-up
measure: Assessment of changes in quality of life
timeFrame: From baseline to the 16 week time-point and from baseline to the 6-month follow-up
measure: Assessment of changes in fatigue
timeFrame: From baseline to the 16 week time point and from baseline to the 6-month follow-up
measure: Assessment of physical activity, defined as minutes spent in moderate-to-vigorous intensity activity
timeFrame: Measurement at three time points, baseline, 16 weeks and 6-month follow-up
measure: Adverse events
timeFrame: Through study completion, an average of 1 year
Locations:
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
Study officials:
affiliation: Norweigan School of Sport Sciences
name: Truls Raastad, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Uppsala University
name: Karin Nordin, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Strandberg E, Vassbakk-Svindland K, Henriksson A, Johansson B, Vikmoen O, Kudren D, Schauer T, Lindman H, Warnberg F, Berntsen S, Demmelmaier I, Nordin K, Raastad T. Effects of heavy-load resistance training during (neo-)adjuvant chemotherapy on muscle cellular outcomes in women with breast cancer. Medicine (Baltimore). 2021 Mar 12;100(10):e24960. doi: 10.1097/MD.0000000000024960.