Investigating the Combined Effects of Protein, Blueberries, and Exercise on Cardiovascular Health and Frailty in Older Nova Scotians (STRONG)

The STudy on bluebeRries, prOteiN, and Exercise for improvinG Frailty and Cardiovascular Disease (STRONG)

Cardiovascular diseases (CVD) are a leading cause of morbidity and mortality worldwide. While CVDs are predominantly diseases of aging, age itself does not predict CVD risk; people age at different rates. Frailty is a state of accelerated aging that increases the risk of adverse health outcomes. Frail people are at higher risk of developing CVDs, experiencing complications, and dying from these diseases than fit people of the same age. Indeed, frailty predicts the likelihood of developing CVD independently of traditional risk factors for CVD. It is known that older women are frailer than men and tend to express CVDs differently than men, but whether relationships between frailty and CVD are sex specific is unclear. It is possible that shared pathophysiological mechanisms such as chronic inflammation may help explain links between CVD and frailty. Importantly, the degree of frailty can be modified by lifestyle interventions. For example, sedentary lifestyles, food insecurity, and suboptimal dietary habits can exacerbate frailty whereas diet and exercise interventions can attenuate frailty.

The investigators propose that a comprehensive health strategy targeting diet and physical activity to reduce frailty will reduce the risk of cardiovascular disease (CVD), thereby promoting healthy aging. Engaging in physical activity (e.g. exercise) helps improve aerobic fitness, increase muscle mass, promote cardiac regeneration, enhance metabolic function, regulate blood pressure, improve insulin sensitivity, reduce inflammation (a key frailty mechanism), and lessen frailty. High-quality dietary protein is essential to maintain muscle mass/function, preserve mobility, attenuate inflammation, and reduce frailty. Packed with antioxidants such as anthocyanins and flavonoids, with high levels of fiber, vitamins, and minerals, blueberries, a local Nova Scotian food, can help lower blood pressure, improve blood vessel function, reduce inflammation, and help the body utilize dietary protein. These are critical aspects of a strong heart and healthy aging. To date, many frailty intervention studies have been limited by small sample sizes, underrepresentation of women, and/or by testing individual lifestyle modifications rather than synergistic effects; additionally, none have investigated how reducing frailty impacts cardiovascular outcomes. Our goal is to determine if a year-long multidomain intervention of protein, blueberries, and exercise reduces frailty and cardiovascular disease risk in older at-risk Nova Scotians of both sexes.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Disease; Frailty
• Intervention / Treatment: Dietary supplement: intervention of protein, blueberries; Behavioral: Exercise training

Detailed Description

The proposed trial is a randomized control trial (RCT) investigating the synergistic effects of protein, blueberries, and resistance plus aerobic training on frailty and cardiovascular health in at-risk Nova Scotians. As frailty and CVD are closely linked, the investigators propose that lifestyle interventions to reduce frailty will improve cardiovascular health in at risk individuals. Studies designed to reduce frailty to date are limited by testing individual lifestyle modifications rather than a prescribed package combining theoretically synergistic treatments and none have investigated effects on cardiovascular health. The investigators have developed a novel packaged intervention of exercise plus protein and blueberries based on their effectiveness as individual treatments and potential for synergy based on complementary biological mechanisms. The investigators will determine whether this prescribed STRONG intervention reduces frailty and improves cardiovascular health in older Nova Scotians by comparing the treatment group with a control group who will receive their usual medical care, as in most pragmatic trials that are performed to determine if an intervention can improve current practice. Usual medical care may differ between participants; it may or may not include diet and exercise recommendations from their physicians. The trial design for the STRONG study is a pragmatic randomized controlled trial on year in length with an additional year of follow-up. The participants will be randomly assigned to one of two groups for 12 months: the control group (n=120 who will receive usual care), or the treatment group (n=120; who will receive the STRONG intervention of protein, blueberries, and exercise). The control group will be tested for fitness, frailty, and cardiovascular health including blood biomarkers and cardiac function (echocardiography). They will be given 'report cards' with their test results to monitor their health; the treatment group will receive the reports cards as well. Exercise intensity will be monitored using the Category Ratio 10 (CR10) ratings of perceived exertion scale. On this scale, exercise should elicit a score of 4-5. All participants will be given a copy of the CR10 scale and taught how to use it. The exercise prescription will be individualized to each participant based on their pre-intervention fitness level, level of frailty and medical history. Progression of the program will be determined on an individual basis. All exercise programs will be designed and supervised by a clinical exercise physiologist. A hybrid approach will be used for the exercise sessions. The participant must attend the first exercise session in person and then can choose to attend subsequent sessions in person (Exercise Lab, Dickson Bldg) and/or virtually. All virtual sessions will be delivered via a secure Nova Scotia Health Zoom link. Having the first session in person gives all participants the opportunity to learn and discuss the exercises in a one-on-one format with the clinical exercise physiologist. After the first session it is expected that there may be multiple study participants in in-person or virtual exercise sessions. It is hypothesized that the addition of blueberries to a regimen of exercise plus protein will have synergistic beneficial effects on frailty and cardiovascular health in older individuals.

Our objectives are:

1. To determine whether the STRONG intervention reduces frailty equally in both sexes.
2. To determine whether this intervention improves cardiovascular health in males and females.
3. To determine whether beneficial effects of this intervention are mediated, in part, by effects on markers of chronic inflammation and whether these effects are sex specific

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Scott A Grandy, PhD; Phone Number: 902-494-4303; Email: Scott.Grandy@Dal.Ca

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Recruiting
      • QEII Health Sciences Centre, Dickson Building
      • Principal Investigator: Scott A Grandy, PhD
      • Contact: Scott Grandy, PhD; Phone Number: 902-494-4303; Email: grandy@dal.ca
      • Contact: Olivia Mercer; Email: STRONG@nshealth.ca

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Must be 65 years of age or above
• Must be willing to participate in a low to moderate exercise program

Exclusion Criteria:

• Medical and cognitive conditions that prevent participation in the intervention
• Allergies and or dislike of blueberries and/or protein powder

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: intervention of protein, blueberries, and exercise; treatment groups will receive the STRONG intervention of 30g/day (1 scoop) of a colorless, tasteless whey protein isolate powder supplement and 1 cup (150 grams) of blueberries per day. They will also participate in three 60-minute multimodal exercise sessions per week. Each session will include a warm-up and cool-down (~5 minutes each), 30 minutes of moderate intensity aerobic exercise and 20 minutes of moderate intensity resistance training. The intervention lasts for 12 months.	Dietary supplement: intervention of protein, blueberries; intervention of 30g/day (1 scoop) of a colorless, tasteless whey protein isolate powder supplement and 1 cup (150 grams) of blueberries per day.; Behavioral: Exercise training; Three 60-minute multimodal exercise sessions per week. Exercise interventions will be individualized to each participant based on their fitness level as per recommended guidelines for older adults. Each session will include a warm-up and cool-down (~5 minutes each), 30 minutes of moderate intensity aerobic exercise and 20 minutes of moderate intensity resistance training.
No Intervention: Control group; Participants receive usual standard of care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Fitness	Assessed using a 6-minute walk test (6MWT). Total distance in meters will be recorded.	Baseline, 3,6,9, and 12 months
Echocardiography	Ejection fraction will be measured in M-mode and global longitudinal strain will be assessed.	Baseline, 12 Months
Inflammatory Markers	Plasma will be obtained from blood samples collected at two time points, pre- and post-intervention. A multiplex assay will be used to quantify anti-inflammatory and inflammatory cytokines in the plasma sample. The following cytokines will be quantified (pg/ml): APRIL / TNFSF13, BAFF / TNFSF13B, sCD30 / TNFRSF8, sCD163, Chitinase-3-like, gp130 / sIL-6Rβ, IFN-α2, IFN-β, IFN-γ, IL-2, sIL-6Rα, IL-8, IL-10, IL-1, IL-12 (p40), IL-12 (p70), IL-19, IL-20, IL-22, IL-26, IL-27 (p28), IL-28A / IFN-λ2, IL-29/IFN-λ1, IL-32, IL-34, IL-35, LIGHT / TNFSF14, MMP-1, MMP-2, MMP-3, Osteocalcin, Osteopontin, Pentraxin-3, sTNF-R1, sTNF-R2, TSLP, TWEAK / TNFSF12.	Baseline, 12 Months
Frailty	Frailty will be assessed using the Clinical Frailty Scale (CFS), Pictorial Fir-Frail Scale (PFFS), and Frailty Index	Baseline, 3,6,9, and 12 months
Cardiovascualr Risk: Blood pressure	Resting blood pressure (systolic/diastolic) will be assessed using an automated blood pressure cuff. Blood pressure will be measure in mm of Hg.	Baseline, 3, 6, 9, 12 months
Cardiovascualr Risk: Lipid Profile	Blood will be drawn by venipuncture and then sent to the hospital lab. There the lipid profile will be determined. Specifically, total cholesterol (mmol/L), triglycerides (mmol/L), low density lipoprotein (mmol/L) and high density lipoprotein (mmol/L) will be quantified.	Baseline, 12 months
Cardiovascualr Risk: Blood glucose	After fasting for 12 hours the participants blood will be drawn by venipuncture. Blood samples will be sent to the hospital lab and fasting glucose (mmol/L) will be assessed.	Baseline, 12 months
Frailty: Clinical Frailty Scale (CFS)	Frailty will be assessed using the CFS. The scale for the assessment ranges from 0 to 9, where 0 represents a robust individual and 9 represents terminally ill. A score of 4 or higher indicates frailty. This is a clinical judgement tool.	Baseline, 3, 6, 9, 12 months
Frailty: Pictorial Fit to frail Scale (PFFS)	Frailty will be assessed with the PFFS. The PFFS is completed by the participant and uses visual images to assess their level of fitness/frailty. There are 14 sets of images on the PFFS. Each set contains 3-4 images and the participant is asked to pick the images that represents how they "usually" feel. The questionnaire is scored out of 43, with higher scores representing a higher degree of frailty.	Baseline, 3, 6, 9, 12 months
Household Foodwork Interactional Assessment 10 Questions (FIA-Q10)	Household foodwork is "all the tasks a household does for eating". This includes the physical parts of foodwork (such as shopping, chopping, cooking, and cleaning) and the mental parts (such as budgeting, monitoring how much food is at home and what is needed, and remembering food allergies and special diets).	Baseline, 6-month, 12-month, 1 year
ASA24 Dietary Assessment Tool		Baseline, 6-month, 12-month, 1-year.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscular Health: Lower Body Strength	Lower body strength will be assessed using the 30 second sit to stand task. The number of times an individual can stand from a seated position will be recorded.	Baseline, 3,6,9, and 12 months
Balance	Single leg balance test. Total time in seconds will be recorded.	Baseline, 3,6,9, and 12 months
Mobility: Lower Body	Lower body mobility will be assessed using the sit & reach test. Reach distance will be measured in centimeters.	Baseline, 3,6,9, and 12 months
Overall Health	Overall health status will be assessed using the Short-Form 36 Health Survey (SF-36) . The SF-36 contains 10 items. The scores range from 0 to 100, with lower scores representing more disability and higher scores representing less disability.	Baseline, 3,6,9, and 12 months
Muscular Health: Upper Body	Upper body strength will be assessed using a hand grip dynamometer. Grip strength will be measured in kg.	Baseline, 3, 6, 9, 12 months
Mobility: Upper Body	Upper body mobility using the shoulder girdle mobility test. The range of motion will be measured in centimeters.	Baseline, 3, 6, 9, and 12 months.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Outcomes	Safety outcomes will be determined by recording the total number of adverse events that occur over the duration of the exercise program. This will be divided by the number of participant hours to determine the number of adverse events/participant hours.	Safety will be assessed at 1,3,6,9, and 12 months.
Study Adherence	Exercise attendance and blueberry/protein consumption will be monitored using an electronic participant logbook.	On the last day of the month particpants will upload the months logbook. (e.g. On November 30th, participant would upload the November logbook). This will be done for every month the participant is in the study (i.e. 12 months).

Collaborators and Investigators

• Sponsor: Nova Scotia Health Authority
• Collaborators: Dalhousie University

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2025
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: November 14, 2024
• First Submitted That Met QC Criteria: November 15, 2024
• First Posted (Actual): November 18, 2024

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Exercise; Obesity; Hypertension; Cardiovascular Disease; Older Adults; Hyperlipidemia; Protein; Frailty; Blueberries; Sedentary Lifestyle
• Additional Relevant MeSH Terms: Vascular Diseases; Pathologic Processes; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Overweight; Dyslipidemias; Lipid Metabolism Disorders; Pathological Conditions, Signs and Symptoms; Behavior; Nutritional and Metabolic Diseases; Signs and Symptoms; Frailty; Obesity; Hypertension; Cardiovascular Diseases; Hyperlipidemias; Motor Activity; Sedentary Behavior; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise; blueberry extract
• Other Study ID Numbers: STRONG_2024-2027

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