Multiple Risk Factor Intervention Trial in Breast Cancer Survivors (MsFITBC)

Multiple Risk Factor Intervention Trial In Breast Cancer Survivors

This study aims to produce new evidence on the efficacy of exercise and diet for cardiometabolic risk reduction in BC survivors. Using a 3-arm RCT with to 6 months of 1) exercise following Health Canada guidelines; 2) the same exercise plus counselling to follow Canada's Dietary Guidelines to improve diet quality; or 3) stretching group, this study will answer the following questions:

• What is the impact of exercise on cardiometabolic health and body composition in BC survivors?
• What is the effect modification of adding a diet quality intervention to exercise on cardiometabolic health and body composition?
• Is there a link between the capacity of skeletal muscle adaptation to exercise (and diet) and insulin resistance in BC survivors?

The investigators hypothesize that: 1) exercise will improve cardiometabolic and body composition outcomes 2) improvements in cardiometabolic outcomes will be enhanced by the addition of diet quality, which will be essential or additive for Matsuda index, metabolic syndrome, Framingham CVD risk, thigh myosteatosis, muscle mass, VO2peak, 3) skeletal muscle insulin signalling transduction will be impaired in BC survivors via dampened expression of insulin-responsive proteins (e.g. GLUT4) and co-occur with impaired muscle quality (e.g., higher rates of fat depots, presence of fibrous tissue) negatively impacting insulin signalling.

Study Overview

• Status: Recruiting
• Conditions: Sedentary Behavior; Metabolic Disturbance; Breast Cancer Female
• Intervention / Treatment: Behavioral: Guidelines-based physical activity; Behavioral: Guidelines-based healthy eating; Behavioral: Stretching exercise

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Amy A Kirkham, PhD; Phone Number: 416-946-4069; Email: amy.kirkham@utoronto.ca
• Study Contact Backup: Name: Jenna B Gillen, PhD; Phone Number: 416-978-3244; Email: jenna.gillen@mail.utoronto.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5S 2C9
      • Recruiting
      • University of Toronto
      • Contact: Amy A. Kirkham, PhD; Phone Number: 416-946-4069; Email: amy.kirkham@utoronto.ca
      • Contact: Jenna B. Gillen, PhD; Phone Number: 416-978-3244; Email: jenna.gillen@utoronto.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Biologically female
• Diagnosis of stage I, II, or III breast cancer, post-menopausal at the time of diagnosis (haven't had a menstrual cycle within 12 months or greater)
• Receipt of aromatase inhibitors for 12 months or more in the past, but do not have to be currently on aromatase inhibitors.
• Willing and able to complete all study assessments
• BMI ≥ 25 kg/m2
• Able to commit to come to the University once per week for 24 weeks.

Exclusion Criteria:

• Received chemotherapy within the past 11 months
• Diagnosed with metastatic cancer
• Currently taking tamoxifen
• Currently receiving chemotherapy, targeted therapy or radiation treatment
• Distant recurrence or diagnosis of metastatic cancer since early-stage breast cancer diagnosis
• Diagnosed cardiovascular diseases, type 2 diabetes, non-alcoholic fatty liver disease, uncontrolled thyroid condition, or respiratory disease (e.g., COPD or severe or uncontrolled asthma).
• Major signs or symptoms of cardiovascular diseases, diabetes, or renal disease (taken from the American College of Sports Medicine's Guidelines for Exercise Testing and Prescription 11th edition Table 2.1: pain or discomfort in the chest, neck, jaw, arms with rest or exercise, shortness of breath at rest or with mild exertion, dizziness or syncope, loss of balance or passing out, ankle edema, palpitations or tachycardia, intermittent claudication, known heart murmur, unusual fatigue with usual activities.)
• American Heart Association's absolute or relative contraindications for symptom-limited maximal exercise testing (myocardial infarction, aortic or coronary artery stenosis, heart failure, pulmonary embolism or deep vein thrombosis, inflammation of the heart (myocarditis, pericarditis, and/or endocarditis), uncontrolled cardiac arrhythmia, advanced or complete electrical heart block, stroke or transient ischemia attack, blood pressure >200mmHg/100mmHg, a cancer diagnosis other than skin cancer)
• Unable to provide informed consent or communicate in English
• Pregnant or breast-feeding currently or in the past 3 months
• Mobility limitations to aerobic exercise (i.e., wheelchair, walker use, limp impeding walking)
• Smoking cigarettes or marijuana within the past 3 months
• Taking exogenous hormones in any format currently or in the past 3 months
• Contraindications to research MRI (e.g., pacemaker, magnetic implants)
• BMI exceeding 40 kg/m2
• Extreme claustrophobia
• Self-report >30 min/week of moderate-to-vigorous intensity aerobic physical activity
• Following a diet that largely restricts entire food groups or time of eating (e.g., vegan, ketogenic, carnivore, one meal a day) in last 3 months
• Experienced significant weight loss (i.e., >5 kg) in past 3 months
• Currently taking weight loss medications
• Diagnosed history of an eating disorder or self-report of potential undiagnosed eating disorder
• Plans to be away/unavailable for a substantial period of the intervention overall (i.e., >4 weeks throughout the 6 months or >2 weeks within the first 12 weeks of the intervention).
• Allergies to local anesthetics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Guidelines-based physical activity; 150 weekly minutes of moderate-intensity aerobic activity and twice weekly whole-body muscle strengthening.	Behavioral: Guidelines-based physical activity; Through a combination of exercise trainer-led in-person and virtual sessions, as well as counselling for independent aerobic exercise, participants will be guided to achieve 150 weekly minutes of moderate-intensity aerobic activity and twice weekly whole-body muscle strengthening.
Experimental: Guidelines-based physical activity and healthy eating; Arm Description: 150 weekly minutes of moderate-intensity aerobic activity and twice weekly whole-body muscle strengthening + counselling to follow Canada's Food Guide.	Behavioral: Guidelines-based physical activity; Through a combination of exercise trainer-led in-person and virtual sessions, as well as counselling for independent aerobic exercise, participants will be guided to achieve 150 weekly minutes of moderate-intensity aerobic activity and twice weekly whole-body muscle strengthening.; Behavioral: Guidelines-based healthy eating; One-on-one phone/virtual counselling from a registered dietitian to change dietary habits to be in line with Canada's Food Guide.
Placebo Comparator: Stretching exercise; Whole-body stretching.	Behavioral: Stretching exercise; Twice weekly virtual instructor-led whole-body stretching.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin resistance	As assessed by the Matsuda Index calculated from an oral glucose tolerance test (OGTT).	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hepatic insulin resistance	Indirectly measured via HOMA-IR using fasting glucose and insulin levels	6 months
Metabolic syndrome severity	Calculated as a z-score to allow for tracking change in the interventions	6 months
Framingham 10-year risk (%)	Calculated using a widely-used standardized scoring system	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiorespiratory fitness	Measured as peak volume of oxygen consumption via indirect calorimetry during a cardiopulmonary exercise test on a treadmill.	6 months
Heart Rate Recovery	Measured as the difference between peak heart rate during the cardiorespiratory fitness test and heart rate 2-minutes after stopping the exercise test.	6 months
Blood Pressure	Measured as the average of the last 5 of 6 blood pressure measurements using an automatic blood pressure device.	6 months
Thigh Myosteatosis	Measured as thigh muscle fat fraction (percent of muscle compartment composed of fat pixels) determined from contiguous axial fat-water separation 3T magnetic resonance images of both thighs.	6 months
Knee flexion and extension (strength and endurance)	Measured using an isokinetic dynamometer (Biodex) to assess peak torque and total work in 30 repetitions of knee flexion.	6 months
Thigh Muscle Volume	Measured determined from contiguous axial fat-water separation 3T magnetic resonance images of both thighs	6 months
Whole-body fat and fat-free mass	Measured using a body composition device (BodPod) to estimate whole body fat (in kg and %) and fat free mass (in kg and %).	6 months
Visceral adipose tissue	Volumes of adipose tissue in the visceral region measured using 3T fat-water separation magnetic resonance imaging	6 months
Liver fat fraction	Measured as percent of liver volume composed of fat pixels determined from 3 slices through the middle of the liver using the PROFIT1 3T magnetic resonance images sequence.	6 months
Body circumferences	Circumferences of the waist, hip and neck, measured using an inelastic tape	6 months
Lipid panel: HDL, LDL, total Cholesterol, Triglycerides	Analyzed from blood serum using a clinical assay at a core lab.	6 months
Hemoglobin A1c	Analyzed from blood plasma using a clinical assay at a core lab.	6 months
Liver enzymes: alanine transaminase (ALT), aspartate aminotransferase (AST), and albumin	Assessment of ALT, AST, and albumin via a fasting blood serum draw, analyzed on a clinical assay at a core lab.	6 months
Liver fibrosis	Liver T1 time evaluated using the PROFIT1 magnetic resonance sequence, validated marker of liver fibrosis.	6 months
Hemoglobin	Assessed using a fasting blood plasma sample in a clinical assay at a core lab.	6 months
Body weight	Assessed using a calibrated scale attached to the BodPod body composition device.	6 months
Body mass index (BMI)	Calculated from a measurement of height using a stadiometer and body weight (detailed above).	6 months
avO2 difference	Calculated as the VO2 from the corresponding workload from the day 1 treadmill test divided by cardiac output at rest, submaximal, and maximal periods of the treadmill test	6 months
Concentration of biochemical markers of skeletal muscle protein content	Measured via western blotting from a skeletal muscle biopsy of the vastus lateralis muscle. Proteins of interest include those found in mitochondria, contractile signaling pathways, insulin signaling pathways, and in glucose and fat metabolism.	6 months
Concentration of biochemical markers of skeletal muscle structure	Measured via immunofluorescence from a skeletal muscle biopsy of the vastus lateralis muscle. Outcomes of interest will focus on indicators of histology of the skeletal muscle in withc a stain would include skeletal muscle capillarization, lipid content, and fiber type and cross-sectional area.	6 months
Concentration of biochemical markers of skeletal muscle enzyme activity	Measured via spectrophotometer to assess the maximal enzyme activity of enzymes involved in skeletal muscle oxidative capacity, from a biopsy of the vastus lateralis muscle.	6 months
Dietary intake	Various components of dietary intake including macronutrients and micronutrients will be assessed through 3-day food records over 2 weekdays and 1 weekend collected using ASA-24 online system.	6 months
Number of participants who met aerobic physical activity prescription	Average adherence to prescribed aerobic physical activity weekly minutes measured via Garmin smartwatch	6 months, 12 months
Number of participants who me the resistance exercise adherence	Average adherence to prescribed resistance exercise activity weekly sessions via an attendance log	6 months, 12 months
Diet quality	An overall measure of alignment with the dietary guidelines measured via the Healthy Eating Food Index-2019 calculated from 3-day diet records	3 months, 6 months, 12 months
Health-related quality of life	Assessed by RAND-36, where an independent score is provided for 8 scales ranging from 0 to 100 and 2 component summary scales ranging from 0-50 with a higher score indicating better quality of life.	3 months, 6 months, 12 months'
Psychosocial stress	Assessed by the perceived stress scale (PSS-14) where individual scores can range from 0 to 56 with higher scores indicating higher perceived stress	3 months, 6 months, 12 months'
Depression & Anxiety	Measured by the Hospital Anxiety and Depression Scale (HADS); score ranges from 0-21 for each of depression and anxiety with a higher score indicating more severe depression or anxiety	3 months, 6 months, 12 months'
Barriers and self-efficacy for physical activity	Assessed by the barriers to self-efficacy scale (BARSE). For each item, participants indicate their confidence to execute the behavior on a 100-point percentage scale comprised of 10-point increments, ranging from 0% (not at all confident) to 100% (highly confident). Total strength for each measure of self-efficacy is then calculated by summing the confidence ratings and dividing by the total number of items in the scale, resulting in a maximum possible efficacy score of 100.	3 months, 6 months, 12 months'
Physical activity motivation	Assessed via the multi-process action control approach, which is a series of questionnaires developed to understand affective attitudes, instrumental attitudes, perceived capability over physical activity, perceived opportunity for physical activity, decisional intentions, behavioural regulation, physical activity habits, and identity around physical activity. Higher scores represent better physical activity motivations. (Reference: Rhodes, R.E. (2017). The evolving understanding of physical activity behavior: A multi-process action control approach. In A. J. Elliot (Ed), Advances in Motivation Science. (pp. 171-205).)	3 months, 6 months, 12 months'
Sleep quality - subjective	Subjectively assessed by the Pittsburgh Sleep Quality Index (PQSI), which measures components of sleep: sleep duration, disturbance, sleep latency, daytime dysfunction due to sleepiness, sleep efficiency, overall sleep quality, and sleep medication use, with higher scores reflecting poorer sleep quality.	3 months, 6 months, 12 months'
Sleep quantity and quality - device measured	Measured via Garmin smartwatch for the total sleep duration and efficiency.	3 months, 6 months, 12 months'
Self-reported physical activity	Assessed by the Recent Physical Activity Questionnaire (RPAQ) that collects information about types and amounts of activity (sedentary and physical activities) over the last 3 months in the following domains: leisure time, occupation, commuting, domestic life, with greater scores indicating longer time engaging in forms of activity.	3 months, 6 months, 12 months'
Concentration of free fatty acids	Assessed using fasting blood serum in a clinical assay.	6 months
Energy Balance	Energy balance will be quantified as: 3-day avg calorie intake - [estimated resting metabolic rate + 3-day avg Garmin estimate of physical activity energy expenditure + 10% of calorie intake (thermic effect of food)].	6 months
Breast Cancer specific related quality of life	Assessed by EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status.	3 months, 6 months, 12 months'
Fatigue	Assessed using the Multidimensional Fatigue Inventory (MFI-20), a 20-item self-assessment questionnaire that uses a 1 to 5 scale to indicate how statements regarding fatigue are representative of a respondent's experience. A higher score is indicative of higher levels of fatigue.	baseline, 3 months, 6 months, 12 months'
Risk of Type 2 Diabetes	The online CANRISK tool (www.healthycanadians.gc.ca/en/canrisk) assigns scores to risk factors for type 2 diabetes (that overlap with cardiovascular disease/cancer), including age, body mass index, MVPA, fruit/vegetable intake, hypertension, pregnancy complications, ethnicity and education, and is validated for Canada's multiethnic population.	baseline, 3 months, 6 months, 12 months'

Collaborators and Investigators

• Sponsor: University of Toronto
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Amy A Kirkham, PhD, University of Toronto

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: May 22, 2024
• First Submitted That Met QC Criteria: June 6, 2024
• First Posted (Actual): June 12, 2024

Study Record Updates

• Last Update Posted (Estimated): October 1, 2025
• Last Update Submitted That Met QC Criteria: September 26, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavior; Sedentary Behavior; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Therapeutics; Physical Therapy Modalities; Patient Care; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Exercise; Muscle Stretching Exercises
• Other Study ID Numbers: REB #45301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No