Breast Cancer
Conditions
Brief summary
Exercise training has beneficial effects in cancer survivors to minimize some of the side effects of cancer and its treatment and improve long-term prognosis, but there are numerous hurdles for individuals diagnosed with, and being treated for, cancer to participate in exercise programs. The goal of this research study is to begin to evaluate whether exercise training via neuromuscular electrical stimulation (NMES) has beneficial effects on skeletal muscle size and function in cancer survivors.
Interventions
DEVICENeuromuscular electrical stimulation
Neuromuscular electrical stimulation will be performed 5 times/week for one hour each day for 2 months.
Sponsors
University of Vermont
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. stage I, II or III breast cancer 2. receiving neoadjuvant or adjuvant chemotherapy with or without radiation 3. a body mass index \<35 kg/m2.
Exclusion criteria
1. metastatic disease, a prior history of cancer, excluding non-melanoma skin cancer, or prior receipt of chemotherapy 2. autoimmune, vascular or neuromuscular disease that could alter skeletal muscle 3. prior knee or hip replacement 4. contraindications for use of neuromuscular electrical stimulation, including an implanted cardiac defibrillator or pacemaker, lower extremity blood clot or coagulopathy 5. pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximal Calcium-activated Tension Single Muscle Fiber Tension | Difference between values at baseline at 2 months | Tension (force per unit muscle fiber cross-sectional area) from segments of chemically-skinned single human muscle fibers will be assessed under maximal calcium-activated condition, with muscle fiber type determined post-measurement by gel electrophoresis |
| Cross-sectional Area of Skeletal Muscle Fibers | Difference between values at baseline at 2 months | Cross-sectional area of skeletal muscle fibers will be evaluated using immunohistochemistry, with specification of all relevant muscle fiber types |
| Intermyofibrillar Mitochondrial Content | Difference between values at baseline at 2 months | Area fraction of intermyofibrillar mitochondria will be assessed by electron microscopy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Single Muscle Fiber Contractile Velocity | Difference between values at baseline at 2 months | Single muscle fiber contractile velocity assessed using isotonic load clamps, with muscle fiber type determined post-measurement by gel electrophoresis. The velocity of contraction is expressed relative to the length of the muscle fiber segment evaluated (as measured using a eyepiece micrometer during assessments) per second. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NMES Neuromuscular electrical stimulation (NMES) group
Neuromuscular electrical stimulation: Neuromuscular electrical stimulation will be performed 5 times/week for one hour each day for 2 months. | 12 |
| Control Control group | 10 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lost to Follow-up | 3 | 1 |
Baseline characteristics
| Characteristic | Total | NMES | Control |
|---|---|---|---|
| Age, Continuous | 54.5 years STANDARD_DEVIATION 7.1 | 53.7 years STANDARD_DEVIATION 5.5 | 55.5 years STANDARD_DEVIATION 8.8 |
| Appendicular skeletal muscle mass | 25.0 kilograms STANDARD_DEVIATION 4.4 | 25.3 kilograms STANDARD_DEVIATION 3.9 | 24.7 kilograms STANDARD_DEVIATION 5.2 |
| Fat-free mass | 41.4 kilograms STANDARD_DEVIATION 5.7 | 41.5 kilograms STANDARD_DEVIATION 5.4 | 41.3 kilograms STANDARD_DEVIATION 6.4 |
| Fat mass | 30.2 kilograms STANDARD_DEVIATION 9.8 | 31.9 kilograms STANDARD_DEVIATION 10.6 | 28.3 kilograms STANDARD_DEVIATION 8.8 |
| Height | 162.6 centimeters STANDARD_DEVIATION 8.8 | 163.4 centimeters STANDARD_DEVIATION 10.5 | 161.6 centimeters STANDARD_DEVIATION 6.9 |
| Percentage of body fat | 41.3 percent STANDARD_DEVIATION 6.5 | 42.4 percent STANDARD_DEVIATION 7 | 39.9 percent STANDARD_DEVIATION 5.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 11 Participants | 9 Participants |
| Region of Enrollment United States | 22 participants | 12 participants | 10 participants |
| Sex: Female, Male Female | 22 Participants | 12 Participants | 10 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Weight | 73.2 kilograms STANDARD_DEVIATION 14.5 | 75.0 kilograms STANDARD_DEVIATION 15.1 | 71.2 kilograms STANDARD_DEVIATION 14.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 10 |
| other Total, other adverse events | 0 / 12 | 1 / 10 |
| serious Total, serious adverse events | 0 / 12 | 1 / 10 |
Outcome results
Primary
Cross-sectional Area of Skeletal Muscle Fibers
Cross-sectional area of skeletal muscle fibers will be evaluated using immunohistochemistry, with specification of all relevant muscle fiber types
Time frame: Difference between values at baseline at 2 months
Population: The sample sizes reflect the number of volunteers with paired data at both baseline and 2-month testing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NMES | Cross-sectional Area of Skeletal Muscle Fibers | Baseline testing | 2432 micrometers^2 | Standard Error 246 |
| NMES | Cross-sectional Area of Skeletal Muscle Fibers | Post-intervention testing | 2694 micrometers^2 | Standard Error 246 |
| Control | Cross-sectional Area of Skeletal Muscle Fibers | Baseline testing | 2320 micrometers^2 | Standard Error 261 |
| Control | Cross-sectional Area of Skeletal Muscle Fibers | Post-intervention testing | 2381 micrometers^2 | Standard Error 260 |
Primary
Intermyofibrillar Mitochondrial Content
Area fraction of intermyofibrillar mitochondria will be assessed by electron microscopy
Time frame: Difference between values at baseline at 2 months
Population: The sample sizes reflect the number of volunteers with paired data at both baseline and 2-month testing and the fact that electron microscopy measures could not be completed on one volunteer because of insufficient muscle tissue.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NMES | Intermyofibrillar Mitochondrial Content | Baseline testing | 2.72 percentage of image area | Standard Error 0.24 |
| NMES | Intermyofibrillar Mitochondrial Content | Post-intervention testing | 2.75 percentage of image area | Standard Error 0.25 |
| Control | Intermyofibrillar Mitochondrial Content | Baseline testing | 2.62 percentage of image area | Standard Error 0.26 |
| Control | Intermyofibrillar Mitochondrial Content | Post-intervention testing | 2.56 percentage of image area | Standard Error 0.26 |
Primary
Maximal Calcium-activated Tension Single Muscle Fiber Tension
Tension (force per unit muscle fiber cross-sectional area) from segments of chemically-skinned single human muscle fibers will be assessed under maximal calcium-activated condition, with muscle fiber type determined post-measurement by gel electrophoresis
Time frame: Difference between values at baseline at 2 months
Population: The sample sizes reflect the number of volunteers with paired data at both baseline and 2-month testing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NMES | Maximal Calcium-activated Tension Single Muscle Fiber Tension | Baseline testing | 185 milliNewtons per millimeter^2 | Standard Error 10 |
| NMES | Maximal Calcium-activated Tension Single Muscle Fiber Tension | Post-intervention testing | 172 milliNewtons per millimeter^2 | Standard Error 9 |
| Control | Maximal Calcium-activated Tension Single Muscle Fiber Tension | Baseline testing | 172 milliNewtons per millimeter^2 | Standard Error 10 |
| Control | Maximal Calcium-activated Tension Single Muscle Fiber Tension | Post-intervention testing | 168 milliNewtons per millimeter^2 | Standard Error 10 |
Secondary
Single Muscle Fiber Contractile Velocity
Single muscle fiber contractile velocity assessed using isotonic load clamps, with muscle fiber type determined post-measurement by gel electrophoresis. The velocity of contraction is expressed relative to the length of the muscle fiber segment evaluated (as measured using a eyepiece micrometer during assessments) per second.
Time frame: Difference between values at baseline at 2 months
Population: The sample sizes reflect the number of volunteers with paired data at both baseline and 2-month testing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NMES | Single Muscle Fiber Contractile Velocity | Baseline testing | 2.1 muscle lengths per second | Standard Error 0.08 |
| NMES | Single Muscle Fiber Contractile Velocity | Post-intervention testing | 1.92 muscle lengths per second | Standard Error 0.9 |
| Control | Single Muscle Fiber Contractile Velocity | Baseline testing | 1.92 muscle lengths per second | Standard Error 0.09 |
| Control | Single Muscle Fiber Contractile Velocity | Post-intervention testing | 1.73 muscle lengths per second | Standard Error 0.8 |