Clinical trial NCT06454864: Multiple Risk Factor Intervention Trial in Breast Cancer Survivors
Official title: Multiple Risk Factor Intervention Trial In Breast Cancer Survivors
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Metabolic Disturbance
Sedentary Behavior
Breast Cancer Female
Lead sponsor: University of Toronto
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2024-06-12
Enrollment: 45
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 3-arm parallel-group randomized controlled trial
Primary purpose: PREVENTION

Brief 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.


Eligibility criteria: 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
* BMI ≥ 25 kg/m2
* Able to commit to come to the University once per week for 24 weeks.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Insulin resistance
timeFrame: 6 months
Secondary outcomes:
measure: Hepatic insulin resistance
timeFrame: 6 months
measure: Metabolic syndrome severity
timeFrame: 6 months
measure: Framingham 10-year risk (%)
timeFrame: 6 months
Other outcomes:
measure: Cardiorespiratory fitness
timeFrame: 6 months
measure: Heart Rate Recovery
timeFrame: 6 months
measure: avO2 difference
timeFrame: 6 months
measure: Blood Pressure
timeFrame: 6 months
measure: Thigh Myosteatosis
timeFrame: 6 months
measure: Knee flexion and extension (strength and endurance)
timeFrame: 6 months
measure: Thigh Muscle Volume
timeFrame: 6 months
measure: Concentration of biochemical markers of skeletal muscle protein content
timeFrame: 6 months
measure: Concentration of biochemical markers of skeletal muscle structure
timeFrame: 6 months
measure: Concentration of biochemical markers of skeletal muscle enzyme activity
timeFrame: 6 months
measure: Whole-body fat and fat-free mass
timeFrame: 6 months
measure: Visceral adipose tissue
timeFrame: 6 months
measure: Liver fat fraction
timeFrame: 6 months
measure: Body circumferences
timeFrame: 6 months
measure: Lipid panel: HDL, LDL, total Cholesterol, Triglycerides
timeFrame: 6 months
measure: Hemoglobin A1c
timeFrame: 6 months
measure: Dietary intake
timeFrame: 6 months
measure: Liver enzymes: alanine transaminase (ALT), aspartate aminotransferase (AST), and albumin
timeFrame: 6 months
measure: Liver fibrosis
timeFrame: 6 months
measure: Number of participants who met aerobic physical activity prescription
timeFrame: 6 months, 12 months
measure: Number of participants who me the resistance exercise adherence
timeFrame: 6 months, 12 months
measure: Diet quality
timeFrame: 3 months, 6 months, 12 months
measure: Health-related quality of life
timeFrame: 3 months, 6 months, 12 months'
measure: Breast Cancer specific related quality of life
timeFrame: 3 months, 6 months, 12 months'
measure: Psychosocial stress
timeFrame: 3 months, 6 months, 12 months'
measure: Depression & Anxiety
timeFrame: 3 months, 6 months, 12 months'
measure: Barriers and self-efficacy for physical activity
timeFrame: 3 months, 6 months, 12 months'
measure: Physical activity motivation
timeFrame: 3 months, 6 months, 12 months'
measure: Sleep quality - subjective
timeFrame: 3 months, 6 months, 12 months'
measure: Sleep quantity and quality - device measured
timeFrame: 3 months, 6 months, 12 months'
measure: Self-reported physical activity
timeFrame: 3 months, 6 months, 12 months'
measure: Hemoglobin
timeFrame: 6 months
measure: Concentration of free fatty acids
timeFrame: 6 months
measure: Body weight
timeFrame: 6 months
measure: Body mass index (BMI)
timeFrame: 6 months
measure: Energy Balance
timeFrame: 6 months
measure: Fatigue
timeFrame: baseline, 3 months, 6 months, 12 months'
measure: Risk of Type 2 Diabetes
timeFrame: baseline, 3 months, 6 months, 12 months'
Locations:
city: Toronto
country: Canada
facility: University of Toronto
state: Ontario
Study officials:
affiliation: University of Toronto
name: Amy A Kirkham, PhD
role: PRINCIPAL_INVESTIGATOR
References: