Heart Rate Variability Guided Physical Activity and Exercise Prescription in Individuals With Knee Osteoarthritis (HOPE-OA)

Heart Rate Variability Guided Optimization of Physical Activity and Exercise Prescription to Enhance Rehabilitation Outcomes in Individuals With Knee Osteoarthritis (HOPE-OA Trial)

The aim of this trial is to conduct a 12-week randomised controlled trial comparing an HRV-guided home exercise program with traditional home exercise program for individuals with knee osteoarthritis (KOA), followed by 24-week assessment. The trial employs a validated HRV sensor and the HRV4Training app to record daily HRV measurements, enabling personalized exercise intensity adjustments. Participants with high HRV are prescribed high-intensity exercises, while those with low HRV undertake low-intensity exercises. In contrast, the traditional exercise group follows a standardised program, progressing from low to high intensity over the 12-week period.

The primary objective of this trial is to evaluate the effect of HRV-guided exercise on pain and functional disability in patients with KOA using validated outcome measures assessed at baseline, 12 weeks (post-intervention), and 24 weeks. Longitudinal semi-structured qualitative interviews at weeks 12 and 24 will explore participants' experiences and perceived barriers to exercise adherence. A mediation analysis will elucidate the physiological mechanisms underlying the efficacy of HRV-guided exercise. Secondary objectives include comparing HRV-guided and traditional home exercise programme in terms of exercise adherence, quality of life, sleep quality, self-efficacy, patient satisfaction, physical performance, balance, muscle strength, and lower limb biomechanics. Exploratory aims involve evaluating long-term effects (up to 24 weeks), examining associations between baseline HRV profiles and key outcomes, and determining the cost-effectiveness of HRV-guided exercise relative to traditional programme. The trial employs a robust methodological design, applying mixed-effects models and an intention-to-treat approach for data analysis.

Study Overview

• Status: Not yet recruiting
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Behavioral: HRV-guided home exercise prescription; Behavioral: Traditional Home Exercise

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

Contacts and Locations

• Study Contact: Name: Shanawaz Anwer, PhD; Phone Number: +85256239232; Email: shah-nawaz.anwer@polyu.edu.hk
• Study Contact Backup: Name: Arnold YL Wong, PhD; Phone Number: +852 2766 6741; Email: arnold.wong@polyu.edu.hk

Study Locations

• Hong Kong
  • Kowloon, Hong Kong
    • Department of Rehabilitation Sciences, The Hong Kong Polytechnic University
    • Contact: Arnold YL Wong, PhD; Phone Number: +852 2766 6741; Email: arnold.wong@polyu.edu.hk
    • Contact: Shahnawaz ANWER, PhD; Phone Number: +85256239232; Email: shah-nawaz.anwer@polyu.edu.hk
    • Principal Investigator: Shahnawaz ANWER, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Participants will include adults aged 45 years and older with symptomatic KOA, diagnosed according to the American College of Rheumatology Clinical Criteria for the Classification and Reporting of KOA.
2. Mild to moderate KOA (Kellgren Lawrence grade ≤ grade III),
3. a body mass index (BMI) ≤ 40 kg/m2, and
4. an average knee pain intensity ≥ 3 on a 0-10 numerical rating scale during the past week.

Exclusion Criteria:

1. presence of neurological disorders;
2. nonambulatory status;
3. implanted electrical devices;
4. systemic inflammatory arthritis (e.g., gout);
5. significant cognitive impairment;
6. prior hip or knee arthroplasty;
7. history of trauma or surgical arthroscopy of either knee within the past six months;
8. participation in a similar study within the past six months;
9. engagement in an exercise programme within the past six months;
10. receipt of knee intra-articular injection within the past three months;
11. current anticoagulant therapy;
12. recent or planned surgery within three months; and
13. any medical comorbidities precluding safe participation in exercise.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HRV guided home exercise	Behavioral: HRV-guided home exercise prescription; Participants in this group will follow the same exercise structure as the traditional home exercise group; however, their exercise program will be individualised according to daily HRV profiles. Exercise sessions will be performed three times per week for 12 weeks (36 sessions). All participants will conduct HRV measurements, starting one week before the intervention and continuing until its completion. HRV will be measured each morning immediately after awakening and bladder voiding, with participants remaining in the supine position for 5 minutes. The validated smartphone application, "HRV4Training" (http://www.hrv4training.com/) will be used to record HRV data [31]. The analysis provides the root mean square of successive differences between R-R intervals (root mean square successive differences [rMSSD]), derived via photoplethysmography. A 7-day rolling average (Ln rMSSD7d) will be computed, and HRV parameters will be calculated.
Active Comparator: Traditional home exercise	Behavioral: Traditional Home Exercise; Participants in this group will measure their HRV daily as described in the next section; however, these HRV measurements will not be used to guide their exercise prescription. Instead, participants will follow a standardized home exercise programme, conducted three sessions per week for 12 weeks (36 sessions). Each session will include a 5-10-minute warm-up, a main exercise component comprising aerobic, strengthening, and stretching exercises (e.g., stretching of lower extremity muscles including knee extensors, knee flexors, and calf), and a 5-minute cooldown [27-29]. The warm-up phase will comprise mobility exercises designed to activate the lower extremity muscles, particularly the quadriceps and hamstrings, while the cool-down will incorporate stretching the muscle groups engaged during the session.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee pain	Assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. Higher scores mean more discomfort. The WOMAC pain subscale include five items for pain (scores range from 0 to 20).	change from pre- to post-treatment (12 weeks)
Physical Function	Assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function subscale. Higher scores mean more difficulty with daily tasks. The WOMAC function subscale include 17 items for functional restriction (scores range from 0 to 68).	Change from pre- to post-treatment (12 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Healthcare resource utilisation	Client service recipient inventory (CSRI) will utilised to assess healthcare resource utilisation.	week 12 and week 24
Quality adjusted life year (QALY)	Quality-adjusted life-years (QALYs) will serve as outcome metric for economic evaluation, derived from the 5-level EuroQol instrument (EQ-5D-5L). Unadjusted mean costs and cost differences between HRV-G and TRD-G exercise groups will be examined for aggregate and disaggregated cost components, including intervention costs, healthcare service use, and pharmaceutical expenditures. Total cost differences (ΔC) and effect differences (ΔE) will be estimated, adjusting for baseline demographic and health characteristics. Responses from the EQ-5D-5L will be converted into utility scores, which will then be used to calculate QALY changes over the study period. The incremental cost-effectiveness ratio (ICER) will be computed using the formula ICER = ΔC/ΔE.	week 12 and week 24
Pittsburgh Sleep Quality Index	The Pittsburgh Sleep Quality Index (PSQI) used to measure the quality and patterns of sleep in adults. It identify sleep quality between "poor" and "good" sleep by utilizing seven domains: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction. A lower PSQI score indicates better sleep quality, with scores of ≤5 considered good and ≥5 indicating poor sleep quality.	Baseline, week 12, week 24
Gait analysis	Motion capture system will be utilized for gait assessment.	changes from baseline to week 12
Quadriceps and Hamstring muscle strength	An isokinetic dynamometry will be used for the assessment of Quadriceps and Hamstring muscle strength	changes from baseline to week 12
Single and double leg standing balance	Bertec balance system will be used for the assessment of Single and double leg standing balance.	changes from baseline to week 12
Heart rate variability (HRV)	All participants will conduct HRV measurements, starting one week before the intervention and continuing until its completion. HRV will be measured each morning immediately after awakening and bladder voiding, with participants remaining in the supine position for 5 minutes. The validated smartphone application, "HRV4Training" (http://www.hrv4training.com/) will be used to record HRV data [31]. The analysis provides the root mean square of successive differences between R-R intervals (root mean square successive differences [rMSSD]), derived via photoplethysmography. The rMSSD is preferred for its reliability over other HRV indices. To normalise data distribution, HRV values will be log-transformed using the natural logarithm (Ln) before statistical analysis. A 7-day rolling average (Ln rMSSD7d) will be computed, and HRV parameters will be calculated during both the familiarization period and on a weekly basis throughout the experimental phase.	Daily
Knee pain	Assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. Higher scores mean more discomfort. The WOMAC pain subscale include five items for pain (scores range from 0 to 20).	changes from baseline to week 24
Physical function	Assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function subscale. Higher scores mean more difficulty with daily tasks. The WOMAC function subscale include 17 items for functional restriction (scores range from 0 to 68).	changes from baseline to week 24
Arthritis self-efficacy scale (ASES)	The Arthritis self-efficacy scale (ASES) consists of 20 items that assess a patient's confidence in controlling pain, physical function, and other disease-related factors. The scale has three parts: pain management, function, and other symptoms like fatigue. Each question asks the respondent to rate their self-efficacy on a scale from 10 to 100, with 10 meaning "very uncertain" and 100 meaning "very certain" about their capacity to do particular tasks or deal with symptoms. Therapists give the questionnaire to patients and tell them to think about how confident they usually feel during the past week when they answer. To get subscale scores, the scores in each domain are added together. Higher scores indicate greater perceived self-efficacy.	Baseline, week 12, week 24
Center for Epidemiologic Studies Depression Scale (CESD)	The Center for Epidemiologic Studies Depression Scale (CESD) is a widely used self-report scale designed to measure depressive symptoms in the general population, consisting of 20 items that assess how often individuals have experienced specific symptoms over the past week. The score is the sum of the 20 questions. Possible range is 0-60. A score of 16 points or more is considered depressed.	Baseline, week 12, week 24
Patient Specific Functional Scale (PSFS)	The Patient Specific Functional Scale (PSFS) is a self-reported valid, reliable, and responsive outcome measure for patients with back, neck, knee and upper extremity problems. It has also been shown to have a high test-retest reliability in both generic lower back pain and knee dysfunction issues. It is also clinically responsive to changes over time with chronic pain patients. Patients are asked to identify up to five important activities they are unable to perform or are having difficulty with as a result of their problem eg putting socks on, shopping. Patients are asked to rate their current level of difficulty associated with each activity on an 11-point scale from 0 (unable to perform) to 10 (able to perform at prior level). Higher the score better the function.	Baseline, week 12, week 24
30 second chair stand test (30sCST)	The 30 second chair stand test (30sCST) requires participants to rise fully from a seated position in an unarmed, straight-backed chair (seat height: 45 cm) and return to a seated position until fully seated. The total number of chair-stand repetitions performed within a 30-s interval will be recorded. Participants will engage in two slow-paced practice repetitions prior to formal testing to ensure comprehension.	changes from baseline to week 12
40-m fast-paced walk test (40MFPW)	The 40-m fast-paced walk test (40MFPW) requires participants to walk as quickly and safely as possible along a 10-m walkway, turning around a cone positioned 2 m beyond each end of the walkway, resulting in a total distance of 40 m. Participants may utilize a walking aid if necessary, and the duration for task completion will be documented [22].	changes from baseline to week 12
Stair-climbing test (SCT)	The stair-climbing test (SCT) will require participants to ascend and descend nine stairs, each with a step height of 20 cm, as quickly as possible while ensuring safety. A handrail will be provided for participants who wish to utilize it or require walking aids. The duration for participants to complete the ascending and descending tasks will be recorded.	changes from baseline to week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
System Usability Scale (SUS)	The feasibility and usability of the HRV device for optimising home exercise programme will be evaluated using the System Usability Scale (SUS). The HRV device will be considered a viable tool for rehabilitation and home exercise optimization in individuals with KOA if it achieves an average SUS score of 70 points or higher.	week 12

Collaborators and Investigators

• Sponsor: The Hong Kong Polytechnic University
• Investigators: Principal Investigator: Shanawaz Anwer, PhD, The Hong Kong Polytechnic University

Publications and helpful links

General Publications

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• 22. Joudeh AA, Alghadir AH, Zafar H, Elwatidy SM, Tse C, Anwer S. Effect of quadriceps and calf muscles fatigue on standing balance in healthy young adult males. Journal of Musculoskeletal & Neuronal Interactions. 2018 Jun;18(2):248.
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Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: January 29, 2026
• First Submitted That Met QC Criteria: January 29, 2026
• First Posted (Actual): February 5, 2026

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Rehabilitation; Physical activity; Knee osteoarthritis; HRV; Home exercise
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Behavior; Osteoarthritis, Knee; Motor Activity
• Other Study ID Numbers: HSEARS20251219004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymised individual participant data that underlie the results reported in publication(s).
• IPD Sharing Time Frame: Beginning 6 months and ending 36 months following publication(s).
• IPD Sharing Access Criteria: Data will only be available for individual participant data. Data will be disseminated to researchers who submit a methodologically rigorous proposal and whose intended usage of the data has received approval from an independent review committee designated for this purpose.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No