Multiple Risk Factor Intervention Trial (Ms. FIT)

Sedentary Behavior Clinical Trial

— MsFIT  

Official title:

Multiple Risk Factor Intervention Trial (Ms. FIT)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06345937
• Other study ID #: REB #44724
• Status: Recruiting
• Phase: N/A
• Start date: May 3, 2024
• Est. completion date: August 1, 2028

Study information

• Verified date: May 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, 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: August 1, 2028
• Est. primary completion date: August 1, 2027
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 30 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Metabolic Disturbance
• Sedentary Behavior

Intervention

Behavioral:
• Behavioural Experimental: 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.
• Behavioural Experimental: guidelines-based physical activity and healthy eating
Behavioural Experimental: 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. Behavioural Experimental: 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.
• Behavioural: 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	Exercise stroke volume & cardiac output	Measured during submaximal and maximal periods of a cycling exercise test, using echocardiography.	6 months
Other	Left ventricular ejection fraction	Measured during rest, submaximal and maximal periods of cycling exercise test, using echocardiography	6 months
Other	Left ventricular mass	Measured via echocardiography at rest	6 months
Other	Arteriovenous Oxygen Difference (avO2diff)	Measured using two methods: (1) calculated as the volume of oxygen (VO2) from the corresponding workload from the day 1 treadmill test divided by cardiac output at rest, submaximal, and maximal periods of the cycling exercise test; and (2) direct assessment using near-infrared spectroscopy as a measure of tissue oxygenation in the legs at rest, submaximal, and maximal periods of the cycling exercise test.	6 months
Other	Endothelial Function	Measured using a brachial artery flow-mediated dilation test using ultrasound.	6 months
Other	Carotid Intima Media Thickness	Measured using a common carotid artery image using ultrasound.	6 months
Other	Central & Peripheral Arterial stiffness	Measured as the pulse wave velocity of the central (carotid-femoral) and peripheral leg (femoral-dorsalis pedis) and arm (carotid-radial) regions.	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	Resting Heart Rate & Heart Rate Variability	Assessed using a 3-lead electrocardiogram in the supine position for 10 minutes after a 5-minute supine rest.	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 3 Tesla (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	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	Biochemical markers of skeletal muscle structure	Measured via immunofluorescence from a skeletal muscle biopsy of the vastus lateralis muscle. Outcomes of interest include skeletal muscle capillarization, lipid content, and fiber type and cross sectional area.	6 months
Other	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	Concentration of inflammation biomarkers in blood	Assessments from blood including leptin, adiponectin, Tumour Necrosis Factor alpha (TNF-a), Interleukin-6 (IL-6), C-reactive protein (CRP). These measures have been grouped together as the markers will be considered together when interpreted.	6 months
Other	Lipid panel: high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, 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 Automated Self-Administered 24hour (ASA-24) online system.	3 months, 6 months, 12 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	Aerobic physical activity adherence	Average adherence to prescribed aerobic physical activity weekly minutes measured via Garmin smart watch	6 months, 12 months
Other	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 Canadian healthy eating index 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	Menopausal symptom presence and severity	Assessed by the Menopause-specific Quality of Life (MENQOL) questionnaire. Each of four domains is constrained between 1 to 8 where a higher score indicates more symptoms.	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 smart watch 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	Serum Estradiol	Assessed using fasting blood serum in a clinical assay.	6 months
Other	Salivary Estradiol	Assessed using a salivary sample in-house using a clinical assay.	6 months
Other	Hemoglobin	Assessed using a fasting blood plasma sample in a clinical assay at a core lab.	6 months
Other	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)].	3 months, 6 months, 12 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