Targeted Ankle Proprioceptive Training Improves Balance, Gait, and Functional Mobility in Chronic Stroke Survivors: A Multicenter Randomized Controlled Trial With Longitudinal Follow Up
Phase: NA
Conditions: Proprioceptive Disorders, Balance; Distorted, Stroke Sequelae
Sponsor: Iqra National University

 
 
Main Mingora Road, Odigram,  
 
Tel: 1946-883946-47 
Swat, Khyber Pakhtunkhwa 
 
Email: info@inuswat.edu.pk 
 
 
Study Protocol Document 
Title: Targeted Ankle Proprioceptive Training to Improve Balance, Gait, and Functional 
Mobility in Chronic Stroke Survivors: A Multicenter Randomized Controlled Trial with 
Longitudinal Follow-Up 
Protocol Version: 1.0 (Pre-trial, submitted for ethics approval) Date: December 2022 Principal 
Investigator: Muslim Khan, Associate Professor, Faculty of Rehabilitation Sciences, IQRA 
National 
University, 
Swat, 
Pakistan 
Email: 
drmuslim17@gmail.com 
/ 
dr.muslim@inuswat.edu.pk ORCID: 0000-0002-9916-9337 
Collaborating Centers: 
• 
Psychiatric Care & Rehabilitation Center (SPCRC), Swat, Pakistan 
• 
Al-Makki Rehabilitation Center, Swat, Pakistan 
• 
Hashoo Foundation Rehabilitation Center & Model Addiction Treatment & 
Rehabilitation Centre (MATRC), Swat, Pakistan 
• 
Saidu Group of Teaching Hospital & IQRA National University, Swat, Pakistan 
• 
Additional sites: Taibah University, Prince Sattam bin Abdulaziz University, Armed 
Forces Hospital Southern Region, Medina Health Cluster, Albaha University, Cairo 
University, King Salman Hospital (Riyadh) 
Trial Registration: OSF [https://osf.io/ps26x/overview] 
Study Design: Multicenter, parallel-group, randomized controlled trial (RCT) with 1:1 
allocation, assessor-blinded, intention-to-treat analysis. Includes a longitudinal observational 
subsample for acute-to-chronic proprioceptive changes. 
Background and Rationale: Stroke is a leading cause of long-term disability, with balance and 
gait deficits affecting >80% of survivors and increasing fall risk. Emerging evidence links ankle 
proprioceptive impairment—particularly inversion/eversion acuity—to these deficits, often 
bilateral and central in origin. Cross-sectional studies show strong associations, but causality, 
temporal progression, and intervention efficacy (especially in severe/non-ambulatory cases) 
remain unproven. This trial tests a targeted proprioceptive protocol against standard care. 
Objectives: Primary: To evaluate the causal effect of 12-week targeted ankle proprioceptive 
training on weight-bearing ankle proprioception (AMEDA) in chronic stroke survivors. 
Secondary: To assess effects on balance (Berg Balance Scale), gait speed (10m walk test), 
mobility (Timed Up and Go, Functional Ambulation Category), lower extremity motor function 
(Fugl-Meyer), and sustainability at 6-month follow-up. To describe longitudinal proprioceptive 
changes in a subsample from acute to chronic stages. Hypothesis: Intervention group will show  

 
 
Main Mingora Road, Odigram,  
 
Tel: 1946-883946-47 
Swat, Khyber Pakhtunkhwa 
 
Email: info@inuswat.edu.pk 
 
significantly greater improvements in proprioception and functional outcomes, mediated by 
inversion proprioception gains. 
 
Participants: Inclusion Criteria: 
• 
Adults ≥18 years 
• 
Chronic ischemic/hemorrhagic stroke (≥12 months post-stroke) 
• 
Moderate-to-severe lower extremity impairment (Fugl-Meyer LE ≤28 or NIHSS motor 
leg ≥2) 
• 
Documented ankle proprioceptive deficit (AMEDA AUC <0.7) 
• 
Ability to follow instructions and provide informed consent 
Exclusion Criteria: 
• 
Acute medical issues (e.g., uncontrolled hypertension) 
• 
Other neurological disorders 
• 
Severe cognitive impairment (MMSE <24) 
• 
Exercise contraindications 
• 
Concurrent conflicting trials 
Sample Size: 140 participants (70 per group), calculated using G*Power for detecting a 5-point 
difference on Berg Balance Scale (SD=8, power=80%, α=0.05, two-tailed), accounting for 20% 
attrition. Oversized by ~40% for subgroup analyses (severity, ambulatory status). Longitudinal 
subsample: n=42 (convenience from acute data availability). 
Randomization and Blinding: 
• 
Computer-generated block randomization (blocks 4–6), stratified by severity and 
ambulatory status. 
• 
Allocation concealment: Sequentially numbered opaque sealed envelopes. 
• 
Blinding: Outcome assessors and data analysts blinded; participants partially (sham 
elements in control); treating therapists not blinded. 
Interventions: Both groups: 12 weeks, 3 sessions/week × 60 min, supervised. Intervention 
Group (n=70): Progressive targeted ankle proprioceptive training: 
• 
Phase 1 (Weeks 1–4): Robotic-assisted sensory discrimination (inversion/eversion, 
plantar/dorsiflexion; reduce angles, remove visual feedback). 
• 
Phase 2 (Weeks 5–8): Functional weight-bearing challenges (e.g., balance boards, 
textured surfaces, dynamic tasks). 
• 
Phase 3 (Weeks 9–12): Advanced integration (e.g., gait with proprioceptive cues, dual-
task). Control Group (n=70): Standard rehabilitation (lower-limb strengthening,  

 
 
Main Mingora Road, Odigram,  
 
Tel: 1946-883946-47 
Swat, Khyber Pakhtunkhwa 
 
Email: info@inuswat.edu.pk 
• 
 
stretching, over-ground gait training per guidelines; no specialized proprioceptive/robotic 
components). Fidelity: Therapist training, session logs, random audits. 
Outcome Measures: Primary: Active Movement Extent Discrimination Apparatus (AMEDA) 
– weight-bearing ankle proprioception (focus on inversion). Secondary: Berg Balance Scale, 
Timed Up and Go, 10-meter walk test (speed), Fugl-Meyer Lower Extremity, Functional 
Ambulation Category. Assessments: Baseline, post-12 weeks, 6-month follow-up. Longitudinal 
subsample assessed from acute (<1 month) to chronic. 
Statistical Analysis Plan: 
• 
Intention-to-treat with last-observation-carried-forward for missing data. 
• 
Primary: Mixed-model ANOVA for group × time effects. 
• 
Secondary: Effect sizes (Cohen's d), mediation analysis (inversion proprioception as 
mediator of functional gains). 
• 
Subgroup analyses: Severity levels. 
• 
Significance: p<0.05, two-tailed. 
Data Management and Monitoring: 
• 
Secure electronic database, double-entry verification. 
• 
No formal DSMB (low-risk intervention); adverse events monitored and reported to 
IRBs. 
• 
Confidentiality per Helsinki Declaration. 
Ethical Considerations: 
• 
Informed written consent from participants (or representatives). 
• 
Right to withdraw at any time. 
• 
Risks: Minimal (standard rehabilitation exercises; monitored for fatigue/pain). 
• 
Benefits: Potential functional improvement. 
• 
Approved by institutional review boards at all centers: Ref#: SGTH/RR-22-234  & Ref#: 
INU/REHAB/XC94 .  
• 
Conducted per Declaration of Helsinki and ICMJE recommendations. 
Timeline: 
• 
Recruitment: January 2023 – June 2024 (planned; actual extended to December 2024 per 
manuscript note). 
• 
Intervention/Follow-up: Up to 6 months post-enrollment. 
• 
Analysis: 2025. 
Funding: No external funding. Conflicts of Interest: None declared. Protocol Amendments: 
Any changes will be documented and reported to ethics committees.