Effects of HIIT on Bone Metabolism in Individuals With Chronic Stroke
NCT Number: NCT06554665
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Stroke|Bone Loss
Interventions: OTHER: High-intensity interval training group|OTHER: Moderate-intensity continuous training group|OTHER: Stretching group
Sponsor: The Hong Kong Polytechnic University
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 66
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: SINGLE (OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-08-20
Completion Date: 2025-02-20
Locations: The Hong Kong Polytechnic University, Kowloon, Hong Kong

Summary:
Objectives: To investigate the effects of high-intensity interval training (HIIT) on bone metabolism in chronic stroke survivors.

Hypothesis to be tested: HIIT, performed on a recumbent stepper, will yield significantly improved results on bone turnover markers in chronic stroke survivors when compared with moderate-intensity continuous training (MICT) Design and subjects: Single-blinded, stratified, randomised, placebo-controlled clinical trial involving 66 chronic stroke survivors who meet our inclusion criteria.

Interventions: Participants will be randomly allocated to either HIIT, MICT, or a stretching group (active control). HIIT and MICT interventions will be performed 3 times per week for 12 consecutive weeks, giving a total of 36 training sessions.

Main outcome measures: Evaluations will be conducted at baseline, at the end of the intervention (week 12), and at an 12-week follow-up (week 24). Primary outcome measures will include bone turnover markers. Secondary outcome measures will include muscle biochemical markers, inflammatory markers, the Neurological Fatigue Index for stroke, cardiopulmonary function, handgrip strength, the 5-times sit-to-stand, the Fugl-Meyer Motor Assessment, the 6-Minute Walking Test, the 10-Meter Walking Test, the Mini Balance Evaluation Systems Test, the Activities-Specific Balance Confidence Scale, the Physical Activity Enjoyment Scale, the Behavioural Regulation Exercise Questionnaire.

Primary Outcome Measures: Change from Baseline in Bone Turnover Markers (BTMs) at Week 12, Target BTMs include:

(i) serum level of carboxy-terminal cross-linking telopeptide of type I collagen (CTX) (ii) serum level of procollagen type I N propeptide (P1NP) (iii) P1NP/CTX ratio

CTX and P1NP are the reference markers of bone resorption and bone formation, respectively. Commercially available enzyme-linked immunosorbent assay (ELISA) kits will be used for the measurements.

P1NP/CTX ratio provides both information about bone formation and bone resorption, indicating an integrated status of bone metabolism.

Change=(Week 12 Level - Baseline Level), Baseline and Week 12|Change from Baseline in Bone Turnover Markers (BTMs) at Week 24, Target BTMs include:

(i) serum level of carboxy-terminal cross-linking telopeptide of type I collagen (CTX) (ii) serum level of procollagen type I N propeptide (P1NP) (iii) P1NP/CTX ratio

CTX and P1NP are the reference markers of bone resorption and bone formation, respectively. Commercially available enzyme-linked immunosorbent assay (ELISA) kits will be used for the measurements.

P1NP/CTX ratio provides both information about bone formation and bone resorption, indicating an integrated status of bone metabolism.

Change=(Week 24 Level - Baseline Level), Baseline and Week 24
Secondary Outcome Measures: Change from Baseline in Muscle Biochemical markers at Week 12, Target muscle biochemical markers include:

(i) serum level of Brain Derived Neurotrophic Factor (BDNF) (ii) serum level of N-terminal Type III Procollagen (PIIINP)

BDNF is a recommended biochemical marker of neuromuscular junctions and neuroinflammation. PIIINP is the biomarker of choice to measure muscle remodelling. Commercially available enzyme-linked immunosorbent assay (ELISA) kits will be used for the measurements.

Change=(Week 12 Level - Baseline Level), Baseline and Week 12|Change from Baseline in Muscle Biochemical markers at Week 24, Target muscle biochemical markers include:

(i) serum level of Brain Derived Neurotrophic Factor (BDNF) (ii) serum level of N-terminal Type III Procollagen (PIIINP)

BDNF is a recommended biochemical marker of neuromuscular junctions and neuroinflammation. PIIINP is the biomarker of choice to measure muscle remodelling. Commercially available enzyme-linked immunosorbent assay (ELISA) kits will be used for the measurements.

Change=(Week 24 Level - Baseline Level), Baseline and Week 24|Change from Baseline in Inflammatory Markers at Week 12, Target inflammatory markers include:

(i) serum level of high Sensitivity C-Reactive Protein (hs-CRP) (ii) serum level of interleukin-6 (IL-6) (iii) serum level of tumour necrosis factor-α (TNF-α)

hs-CRP, IL-6, and TNF-α are recommended biochemical markers of chronic inflammation. Commercially available turbidimetric immunoassay kits will be used for hs-CRP measurements, while enzyme-linked immunosorbent assay (ELISA) kits will be used for IL-6 and TNF-α measurements.

Change=(Week 12 Level - Baseline Level), Baseline and Week 12|Change from Baseline in Inflammatory Markers at Week 24, Target inflammatory markers include:

(i) serum level of high Sensitivity C-Reactive Protein (hs-CRP) (ii) serum level of interleukin-6 (IL-6) (iii) serum level of tumour necrosis factor-α (TNF-α)

hs-CRP, IL-6, and TNF-α are recommended biochemical markers of chronic inflammation. Commercially available turbidimetric immunoassay kits will be used for hs-CRP measurements, while enzyme-linked immunosorbent assay (ELISA) kits will be used for IL-6 and TNF-α measurements.

Change=(Week 24 Level - Baseline Level), Baseline and Week 24|Change from Baseline in Post-Stroke Fatigue at Week 12, Post-stroke fatigue will be measured by the Chinese Version of the Neurological Fatigue Index for stroke (C-NFI-Stroke). The C-NFI-Stroke is a validated measurement tool for post-stroke fatigue. Possible responses to each item range from 0 (strongly disagree) to 3 (strongly agree). The higher the score, the more severe the fatigue.

Change=(Week 12 Score- Baseline Score), Baseline and Week 12|Change from Baseline in Post-Stroke Fatigue at Week 24, Post-stroke fatigue will be measured by the Chinese Version of the Neurological Fatigue Index for stroke (C-NFI-Stroke). The C-NFI-Stroke is a validated measurement tool for post-stroke fatigue. Possible responses to each item range from 0 (strongly disagree) to 3 (strongly agree). The higher the score, the more severe the fatigue.

Change=(Week 24 Score - Baseline Score), Baseline and Week 24|Change from Baseline in Cardiopulmonary Function at Week 12, Cardiopulmonary function quantified as peak oxygen uptake (VO2peak), will be measured in a graded exercise test (GXT). The GXT will be conducted using a well-validated protocol that uses a whole-body recumbent stepper to assess patients with stroke.

Change=(Week 12 VO2peak - Baseline VO2peak), Baseline and Week 12|Change from Baseline in Cardiopulmonary Function at Week 24, Cardiopulmonary function quantified as peak oxygen uptake (VO2peak), will be measured in a graded exercise test (GXT). The GXT will be conducted using a well-validated protocol that uses a whole-body recumbent stepper to assess patients with stroke.

Change=(Week 24 VO2peak - Baseline VO2peak), Baseline and Week 24|Change from Baseline in Muscle Strength at Week 12, Muscle strength will be quantified through handgrip strength and the time taken to perform the 5-times sit-to-stand test.

Handgrip strength will be measured using a handheld dynamometer. The assessor will provide verbal encouragement to ensure the subjects exert their maximum effort.

Change=(Week 12 Strength - Baseline Strength)

The 5-times sit-to-stand test is a practical measure of lower limb strength. It requires the subject to stand up and sit down five times as quickly as possible from a standard chair. The time taken to complete the task is recorded.

Change=(Week 12 Time - Baseline Time)

For both tests, a practice trial will be provided before the measurements are recorded. Three formal trials will be conducted with a 1-minute rest period in between. The average value of the three trials will be used for analysis., Baseline and Week 12|Change from Baseline in Muscle Strength at Week 24, Muscle strength will be quantified through handgrip strength and the time taken to perform the 5-times sit-to-stand test.

Handgrip strength will be measured using a handheld dynamometer. The assessor will provide verbal encouragement to ensure the subjects exert their maximum effort.

Change=(Week 24 Strength - Baseline Strength)

The 5-times sit-to-stand test is a practical measure of lower limb strength. It requires the subject to stand up and sit down five times as quickly as possible from a standard chair. The time taken to complete the task is recorded.

Change=(Week 24 Time - Baseline Time)

For both tests, a practice trial will be provided before the measurements are recorded. Three formal trials will be conducted with a 1-minute rest period in between. The average value of the three trials will be used for analysis., Baseline and Week 24|Change from Baseline in Muscle Quantity at Week 12, Muscle quantity, quantified as whole-body skeletal muscle mass, will be measured by bioelectrical impedance analysis (BIA). BIA is a recommended equipment that estimates muscle mass based on the electrical conductivity of the whole body.

Change=(Week 12 Muscle Mass - Baseline Muscle Mass), Baseline and Week 12|Change from Baseline in Muscle Quantity at Week 24, Muscle quantity, quantified as whole-body skeletal muscle mass, will be measured by bioelectrical impedance analysis (BIA). BIA is a recommended equipment that estimates muscle mass based on the electrical conductivity of the whole body.

Change=(Week 24 Muscle Mass - Baseline Muscle Mass), Baseline and Week 24|Change from Baseline in Motor Recovery at Week 12, Fugl-Meyer Motor Assessment (FMA) will be used to assess the degree of motor recovery of the hemiparetic upper (range: 0-66) and lower limbs (range: 0-34). Higher scores are indicative of better motor recovery.

Change=(Week 12 Score - Baseline Score), Baseline and Week 12|Change from Baseline in Motor Recovery at Week 24, Fugl-Meyer Motor Assessment (FMA) will be used to assess the degree of motor recovery of the hemiparetic upper (range: 0-66) and lower limbs (range: 0-34). Higher scores are indicative of better motor recovery.

Change=(Week 24 Score- Baseline Score), Baseline and Week 24|Change from Baseline in Walking Function at Week 12, Walking function will be assessed by walking endurance and walking speed.

Walking endurance will be assessed using the 6-Minute Walking Test. Participants will walk at their comfortable speed in a 30-meter-long corridor for 6 minutes, and the distance covered will be recorded.

Change=(Week 12 Time - Baseline Time)

The comfort and fast walking speeds will be assessed using the 10-Meter Walking Test. The participants will be asked to perform this test three times and the mean test time will be calculated. Assistive devices can be used, which will be documented and kept consistent for all time points.

Change=(Week 12 Time - Baseline Time), Baseline and Week 12|Change from Baseline in Walking Function at Week 24, Walking function will be assessed by walking endurance and walking speed.

Walking endurance will be assessed using the 6-Minute Walking Test. Participants will walk at their comfortable speed in a 30-meter-long corridor for 6 minutes, and the distance covered will be recorded.

Change=(Week 24 Time - Baseline Time)

The comfort and fast walking speeds will be assessed using the 10-Meter Walking Test. The participants will be asked to perform this test three times and the mean test time will be calculated. Assistive devices can be used, which will be documented and kept consistent for all time points.

Change=(Week 24 Time - Baseline Time), Baseline and Week 24|Change from Baseline in Balance at Week 12, Balance will be assessed by balance performance and fear of falling.

Balance performance will be measured using the Mini Balance Evaluation Systems Test, which includes 14 dynamic balance activities. The total score ranges from 0 (poor balance) to 28 (good balance).

Change=(Week 12 Score - Baseline Score)

Fear of falling will be evaluated using the Activities-Specific Balance Confidence Scale, which measures an individual's perception of balance confidence for sixteen ambulatory activities that occur in daily life. Individuals will estimate their confidence in maintaining balance using a scale from 0 ("not confident") to 100% ("completely confident")

Change=(Week 12 Score - Baseline Score), Baseline and Week 12|Change from Baseline in Balance at Week 24, Balance will be assessed by balance performance and fear of falling.

Balance performance will be measured using the Mini Balance Evaluation Systems Test, which includes 14 dynamic balance activities. The total score ranges from 0 (poor balance) to 28 (good balance).

Change=(Week 24 Score - Baseline Score)

Fear of falling will be evaluated using the Activities-Specific Balance Confidence Scale, which measures an individual's perception of balance confidence for sixteen ambulatory activities that occur in daily life. Individuals will estimate their confidence in maintaining balance using a scale from 0 ("not confident") to 100% ("completely confident")

Change=(Week 24 Score - Baseline Score), Baseline and Week 24|Change from Baseline in Psychosocial Response at Week 12, Psychosocial response will be assessed by the Physical Activity Enjoyment Scale and Behavioural Regulation Exercise Questionnaire-3.

Physical Activity Enjoyment Scale will be used to measure exercise enjoyment (score range: 0 to 400). Higher scores indicate a higher activity enjoyment level.

Change=(Week 12 Score - Baseline Score)

Motivation for exercise will be assessed using the Behavioural Regulation Exercise Questionnaire-3 which is a 24-item questionnaire (range: 0-96) that examines six different forms of motivational regulation. A higher score represents more motivation to exercise.

Change=(Week 12 Score - Baseline Score), Baseline and Week 12|Change from Baseline in Psychosocial Response at Week 24, Psychosocial response will be assessed by the Physical Activity Enjoyment Scale and Behavioural Regulation Exercise Questionnaire-3.

Physical Activity Enjoyment Scale will be used to measure exercise enjoyment (score range: 0 to 400). Higher scores indicate a higher activity enjoyment level.

Change=(Week 24 Score - Baseline Score)

Motivation for exercise will be assessed using the Behavioural Regulation Exercise Questionnaire-3 which is a 24-item questionnaire (range: 0-96) that examines six different forms of motivational regulation. A higher score represents more motivation to exercise.

Change=(Week 24 Score - Baseline Score), Baseline and Week 24