Multiple Risk Factor Intervention Trial in Breast Cancer Survivors

Breast Cancer Female Clinical Trial

— MsFITBC  

Official title:

Multiple Risk Factor Intervention Trial In Breast Cancer Survivors

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06454864
• Other study ID #: REB #45301
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2024
• Est. completion date: June 1, 2028

Study information

• Verified date: June 2024
• Source: University of Toronto
• Contact: Amy A Kirkham, PhD
• Phone: 416-946-4069
• Email: amy.kirkham[@]utoronto.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 45
• Est. completion date: June 1, 2028
• Est. primary completion date: June 1, 2027
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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) Received chemotherapy and completed it at least 1 and up to 10 years prior

• 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

• High CANRISK score (score of =33)

• 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.

• Able to commit to come to the University once per week for 24 weeks.

Exclusion Criteria:

• Has previously received 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

Related Conditions & MeSH terms

• Breast Cancer Female
• Breast Neoplasms
• Metabolic Disturbance
• Sedentary Behavior

Intervention

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.
• 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.
• Stretching exercise
Twice weekly virtual instructor-led whole-body stretching.

Locations

Country	Name	City	State
Canada	University of Toronto	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
University of Toronto	Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cardiorespiratory fitness	Measured as peak volume of oxygen consumption via indirect calorimetry during a cardiopulmonary exercise test on a treadmill.	6 months
Other	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
Other	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
Other	Blood Pressure	Measured as the average of the last 5 of 6 blood pressure measurements using an automatic blood pressure device.	6 months
Other	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
Other	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
Other	Thigh Muscle Volume	Measured determined from contiguous axial fat-water separation 3T magnetic resonance images of both thighs	6 months
Other	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
Other	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
Other	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
Other	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
Other	Visceral adipose tissue	Volumes of adipose tissue in the visceral region measured using 3T fat-water separation magnetic resonance imaging	6 months
Other	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
Other	Body circumferences	Circumferences of the waist, hip and neck, measured using an inelastic tape	6 months
Other	Lipid panel: HDL, LDL, total Cholesterol, Triglycerides	Analyzed from blood serum using a clinical assay at a core lab.	6 months
Other	Hemoglobin A1c	Analyzed from blood plasma using a clinical assay at a core lab.	6 months
Other	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
Other	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
Other	Liver fibrosis	Liver T1 time evaluated using the PROFIT1 magnetic resonance sequence, validated marker of liver fibrosis.	6 months
Other	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
Other	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
Other	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
Other	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'
Other	Breast Cancer specific related quality of life	Assessed by EORTC QLQ-C30 + BR23 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'
Other	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'
Other	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'
Other	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'
Other	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'
Other	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'
Other	Sleep quantity and quality - device measured	Measured via Garmin smartwatch for the total sleep duration and efficiency.	3 months, 6 months, 12 months'
Other	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'
Other	Hemoglobin	Assessed using a fasting blood plasma sample in a clinical assay at a core lab.	6 months
Other	Concentration of free fatty acids	Assessed using fasting blood serum in a clinical assay.	6 months
Other	Body weight	Assessed using a calibrated scale attached to the BodPod body composition device.	6 months
Other	Body mass index (BMI)	Calculated from a measurement of height using a stadiometer and body weight (detailed above).	6 months
Other	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
Primary	Insulin resistance	As assessed by the Matsuda Index calculated from an oral glucose tolerance test (OGTT).	6 months
Secondary	Hepatic insulin resistance	Indirectly measured via HOMA-IR using fasting glucose and insulin levels	6 months
Secondary	Metabolic syndrome severity	Calculated as a z-score to allow for tracking change in the interventions	6 months
Secondary	Framingham 10-year risk (%)	Calculated using a widely-used standardized scoring system	6 months