Clinical trial NCT06345937: Multiple Risk Factor Intervention Trial (Ms. FIT)
Official title: Multiple Risk Factor Intervention Trial (Ms. FIT)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Metabolic Disturbance
Sedentary Behavior
Keywords: Primary Prevention
Lead sponsor: University of Toronto
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2024-04-03
Enrollment: 180
Sex: FEMALE
Minimum age (years): 30
Standard ages: 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, specific to women, on the efficacy and mechanisms of exercise and diet for cardiometabolic risk reduction in pre and postmenopausal women. Using a 3-arm randomized controlled trial (RCT) with equal recruitment and stratification by menopausal status 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:

* How does the impact of exercise compare among each of the causal links between physical inactivity and cardiometabolic disease in women?
* What is the effect modification of adding a diet quality intervention to exercise?
* What is the effect modification by menopausal status?

The investigators hypothesize that exercise adaptations will be: 1) largest peripherally, including Matsuda index (primary outcome), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), arteriovenous oxygen difference (avO2diff), and visceral fat, compared to centrally (stroke volume (SV), endothelial function, aortic stiffness), 2) blunted or absent in post vs premenopause; 3) enhanced by the addition of diet quality which will be essential or additive for Matsuda index, metabolic syndrome, Framingham cardiovascular disease (CVD) risk, cytokines and adipokines, thigh myosteatosis, muscle mass, peak oxygen uptake (VO2peak), 4) enhanced by adding diet quality in more outcomes postmenopause.


Eligibility criteria: Inclusion Criteria:

* Biologically female
* Aged 30+
* Pre- or postmenopausal: Premenopause: having regular menstrual cycles (21-35 days long without a persistent difference of ≥7 days between cycles). Post-menopause: ≥12 months of amenorrhea or history of double oophorectomy and do not have irregular or occasional menstrual cycle in last 12 months.
* 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, moderate-vigorous physical activity (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:

* Perimenopausal or those whom the investigators cannot discern pre- vs perimenopausal status
* Diagnosed cardiovascular diseases, type 2 diabetes, non-alcoholic fatty liver disease, cancer (except for non-melanoma skin cancer), or respiratory disease (e.g., Chronic obstructive pulmonary disease (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 arrythmia, 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
* Students in classes or labs of the professors who are involved in the study
* 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: Exercise stroke volume & cardiac output
timeFrame: 6 months
measure: Left ventricular ejection fraction
timeFrame: 6 months
measure: Left ventricular mass
timeFrame: 6 months
measure: Arteriovenous Oxygen Difference (avO2diff)
timeFrame: 6 months
measure: Endothelial Function
timeFrame: 6 months
measure: Carotid Intima Media Thickness
timeFrame: 6 months
measure: Central & Peripheral Arterial stiffness
timeFrame: 6 months
measure: Blood Pressure
timeFrame: 6 months
measure: Resting Heart Rate & Heart Rate Variability
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: Biochemical markers of skeletal muscle protein content
timeFrame: 6 months
measure: Biochemical markers of skeletal muscle structure
timeFrame: 6 months
measure: 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: Concentration of inflammation biomarkers in blood
timeFrame: 6 months
measure: Lipid panel: high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total Cholesterol, Triglycerides
timeFrame: 6 months
measure: Hemoglobin A1c
timeFrame: 6 months
measure: Dietary intake
timeFrame: 3 months, 6 months, 12 months
measure: Liver enzymes: alanine transaminase (ALT), aspartate aminotransferase (AST), and albumin
timeFrame: 6 months
measure: Liver fibrosis
timeFrame: 6 months
measure: Aerobic physical activity adherence
timeFrame: 6 months, 12 months
measure: 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: Menopausal symptom presence and severity
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: Serum Estradiol
timeFrame: 6 months
measure: Salivary Estradiol
timeFrame: 6 months
measure: Hemoglobin
timeFrame: 6 months
measure: Free fatty acids
timeFrame: 6 months
measure: Body weight
timeFrame: 6 months
measure: Body mass index (BMI)
timeFrame: 6 months
measure: Energy Balance
timeFrame: 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: