Walking Function Outcomes Following Surgical Correction With Rehabilitation Versus Physical Therapy Alone in Charcot-Marie-Tooth Disease: A Bidirectional Cohort Study (CMT-WALK)

The goal of this study is to compare changes in walking ability in people with Charcot-Marie-Tooth disease (CMT) who receive two different treatment approaches for foot deformities that affect walking.

CMT is an inherited nerve condition that can cause muscle weakness, loss of sensation, and foot deformities. These changes often make walking difficult and can reduce independence and quality of life. Treatment options commonly include physical therapy alone or surgery to correct foot alignment followed by rehabilitation. However, it is not clear whether one approach leads to better long-term walking outcomes.

The main question this study aims to answer is whether individuals who undergo functional foot surgery followed by rehabilitation experience different changes in walking ability over time compared with those who receive structured physical therapy alone.

Researchers will compare walking performance between these two treatment groups over a period of up to two years. Walking ability will be evaluated using standardized walking tests and patient questionnaires.

Participants included in this study are individuals with CMT-related foot deformities that affect walking and who received either surgery followed by rehabilitation or physical therapy alone. Researchers will analyze changes in walking ability over time and determine how many participants achieve meaningful improvement.

The findings from this study may help clinicians and individuals with CMT better understand how different treatment strategies influence walking function over time.

Study Overview

• Status: Not yet recruiting
• Conditions: Surgery; Exercise Training; Gait Disorders; Charcot Marie Tooth Disease (CMT); Pes Cavovarus; Neuromuscular Diseases (NMD)
• Intervention / Treatment: Procedure: Functional Surgery plus Rehabilitation; Behavioral: Physical Exercise

Detailed Description

Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous inherited peripheral neuropathy characterized by progressive distal muscle weakness, sensory impairment, and neuromuscular foot deformities. These impairments frequently alter gait mechanics and reduce walking capacity. In the absence of disease-modifying therapies, clinical management focuses on optimizing functional mobility and mitigating secondary musculoskeletal consequences.

Both conservative physical therapy and functional surgical correction followed by rehabilitation are widely used to address gait-limiting deformities in CMT. Physical therapy primarily targets strength, balance, and motor control, whereas surgical intervention aims to improve structural alignment and rebalance muscle-tendon forces. Despite routine implementation of both approaches, comparative evidence regarding their longitudinal effects on objective walking performance remains limited.

This study uses a bidirectional observational cohort design integrating retrospectively ascertained treatment exposure with prospectively collected longitudinal outcomes. Individuals with CMT-related foot deformities affecting walking who were treated between January 2017 and January 2024 were identified from an institutional clinical database. Participants were classified according to treatment strategy: (1) functional surgical correction followed by standardized postoperative rehabilitation, or (2) structured physical therapy alone. Treatment allocation was determined by routine clinical decision-making rather than randomization.

To address confounding inherent in nonrandomized comparisons, propensity score matching was applied to balance baseline demographic and disease-related characteristics between treatment groups. Covariates included factors such as age at presentation, genetic subtype when available, and baseline disease severity. Balance diagnostics were assessed to confirm adequate group comparability following matching.

The primary focus of the study is longitudinal walking performance. Standardized performance-based assessments of habitual walking speed and functional walking capacity were administered at baseline and during follow-up. A multidimensional framework was used to capture impairment-level measures, task-specific walking performance, and patient-reported health status, enabling evaluation of both functional change and broader clinical impact.

Follow-up assessments were conducted at prespecified intervals up to 2 years after treatment initiation. Baseline data were extracted from electronic medical records, and follow-up data were collected prospectively through structured outpatient assessments and standardized remote evaluations when necessary. Consistent assessment procedures were implemented across time points to enhance reproducibility.

Longitudinal analyses were performed using repeated-measures modeling to evaluate within- and between-group changes over time, with particular emphasis on group-by-time interactions. Multivariable regression analyses were conducted to explore associations between treatment strategy and changes in walking performance while adjusting for relevant clinical covariates. Clinically meaningful improvement was evaluated using established minimal clinically important difference thresholds for walking-related outcomes. Missing data were handled using multiple imputation techniques.

Quality assurance procedures included standardized evaluator training, predefined analytic plans, and structured data management processes to minimize bias and enhance methodological rigor.

Through this longitudinal and performance-centered design, the study aims to clarify the functional consequences of surgical and conservative management strategies for gait-limiting CMT-related foot deformities and to better characterize the trajectory and clinical relevance of walking outcomes over time.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Zhuoqi Wei, MD; Phone Number: +8613838384087; Email: 13838384087@163.com
• Study Contact Backup: Name: Yang Lv, MD, PhD; Phone Number: +8618513112060; Email: lvyang42@126.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study population comprises adults with Charcot-Marie-Tooth disease (CMT) evaluated and treated at a tertiary referral center specializing in neuromuscular and foot and ankle disorders. Participants were identified from consecutive clinical encounters beginning in February 2017, incorporating both retrospectively and prospectively collected data. Eligible individuals had a genetically or clinically confirmed diagnosis of CMT and presented with foot deformity and gait impairment attributable to peripheral neuropathy. All participants were ambulatory, with or without assistive devices, at the time of enrollment. Management strategies included functional surgical intervention followed by rehabilitation or structured physical therapy alone, reflecting routine clinical practice. Longitudinal outcome data were obtained through standardized assessments conducted at baseline and predefined follow-up time points throughout the study period.

Description

Inclusion Criteria:

• Participants aged 12 years or older at the time of enrollment
• Genetically or clinically confirmed CMT, based on established diagnostic criteria
• Presence of foot deformity and/or gait impairment attributable to CMT, as determined by a treating clinician
• Ability to ambulate at least 10 meters, with or without assistive devices
• Medically eligible for either functional surgical intervention or structured physical therapy, as determined by the treating team
• Willingness and ability to participate in longitudinal follow-up assessments
• Provision of written informed consent

Exclusion Criteria:

• Previous major foot or ankle surgery that substantially altered lower-limb biomechanics
• Presence of non-CMT-related neurological disorders affecting gait (eg, stroke, Parkinson disease, multiple sclerosis)
• Severe musculoskeletal conditions unrelated to CMT that limit walking ability (eg, advanced hip or knee osteoarthritis)
• Active lower-limb infection, ulceration, or acute injury at the time of enrollment
• Severe cognitive impairment or psychiatric condition precluding reliable participation
• Medical contraindications to surgery or exercise-based rehabilitation, when relevant
• Inability to complete baseline functional assessments or anticipated inability to complete follow-up

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Functional Surgery plus Rehabilitation (FS Group)	Procedure: Functional Surgery plus Rehabilitation; FS group underwent individualized surgical correction aimed at improving foot alignment, restoring muscle-tendon balance, and optimizing walking mechanics. Surgical procedures included soft tissue release, tendon transfers to augment weakened muscles, and calcaneal osteotomy for hindfoot malalignment. Arthrodesis was reserved for rigid deformities or painful osteoarthritis not amenable to realignment. All surgically treated participants followed a standardized postoperative rehabilitation program, consisting of an initial 2-week period of immobilization with non-weight-bearing, followed by partial weight-bearing with a removable orthosis from weeks 2 to 6, progression to full weight-bearing between weeks 6 and 12, and a structured rehabilitation phase from weeks 12 to 24 emphasizing strengthening, balance training, and task-specific gait retraining. Afterward, participants continued rehabilitation using the same protocol applied to the physical therapy group.
Physical Exercise Alone (PE Group)	Behavioral: Physical Exercise; Participants in the PE group received structured physical therapy without surgical intervention. Programs were individualized based on disease severity and functional capacity to improve walking ability, balance, and lower-limb coordination. Therapy included aerobic exercise, ankle mobility exercises, lower-limb stretching, and balance training, all performed within the available range of motion. After an initial supervised phase, participants transitioned to a home-based, self-supervised program performed approximately twice weekly for up to 12 months. Aerobic training was conducted at moderate intensity using a stationary bicycle or seated alternatives when needed. Exercises were modified as necessary to avoid pain or excessive fatigue.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the 10-Meter Walk Test (10MWT)	Habitual walking speed was determined using the 10-Meter Walk Test (10MWT) and expressed in meters per second (m/s), with higher values reflecting faster walking speed.	baseline (prior to treatment initiation), 6 months, 1 year, and 2 years after treatment initiation
the 6-Minute Walk Test (6MWT)	Functional walking capacity was assessed using the 6-Minute Walk Test (6MWT) and expressed in meters walked during 6 minutes, with higher values reflecting greater walking endurance.	baseline (prior to treatment initiation), 6 months, 1 year, and 2 years after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the Walk-12 Questionnaire	Walking-related disability was assessed using the 12-item Walk-12 questionnaire and expressed as total score according to standardized scoring procedures, with higher scores reflecting greater perceived walking limitation.	baseline (prior to treatment initiation), 6 months, 1 year, and 2 years after treatment initiation
the Foot and Ankle Disability Index (FADI)	Foot and ankle-specific functional status was assessed using the Foot and Ankle Disability Index (FADI) and expressed as total score according to standardized scoring procedures, with higher scores reflecting better function.	baseline (prior to treatment initiation), 6 months, 1 year, and 2 years after treatment initiation
the American Orthopaedic Foot and Ankle Society (AOFAS) Hindfoot Score	Hindfoot function was assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) Hindfoot Score and expressed in points on a 0-100 scale, with higher scores reflecting better clinical function.	baseline (prior to treatment initiation), 6 months, 1 year, and 2 years after treatment initiation
the 12-Item Short Form Health Survey (SF-12)	Health-related quality of life was assessed using the 12-Item Short Form Health Survey (SF-12), including Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, expressed in standardized score units, with higher scores reflecting better health status.	baseline (prior to treatment initiation), 6 months, 1 year, and 2 years after treatment initiation
the Charcot-Marie-Tooth Examination Score (CMTES)	Disease severity was assessed using the Charcot-Marie-Tooth Examination Score (CMTES) and expressed as total score according to standardized scoring criteria, with higher scores reflecting greater disease severity.	baseline (prior to treatment initiation), 6 months, 1 year, and 2 years after treatment initiation
Lower Limb Muscle Strength (Medical Research Council Scale)	Lower limb muscle strength was assessed using the Medical Research Council (MRC) grading scale and expressed as muscle strength grade, with higher grades reflecting greater muscle strength.	baseline (prior to treatment initiation), 6 months, 1 year, and 2 years after treatment initiation
Ankle Joint Range of Motion	Ankle dorsiflexion and plantarflexion range of motion were measured using a goniometer and expressed in degrees, with higher values reflecting greater joint mobility.	baseline (prior to treatment initiation), 6 months, 1 year, and 2 years after treatment initiation
the Incidence of Disease-Related Clinical Symptoms	The occurrence of disease-related clinical symptoms, including ankle sprain, plantar callus formation, foot pain, and limping, was assessed by structured patient report and clinical record review. The outcome was expressed as the number of participants experiencing each symptom during the follow-up period. Higher values reflect greater symptom burden.	baseline (prior to treatment initiation), 6 months, 1 year, and 2 years after treatment initiation

Collaborators and Investigators

• Sponsor: Peking University Third Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 11, 2026
• Primary Completion (Estimated): February 10, 2027
• Study Completion (Estimated): February 10, 2028

Study Registration Dates

• First Submitted: February 11, 2026
• First Submitted That Met QC Criteria: February 24, 2026
• First Posted (Actual): February 25, 2026

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Physical therapy; Charcot Marie Tooth disease; Gait impairment; Walking performance; Propensity score matching; Functional surgery
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Peripheral Nervous System Diseases; Neurodegenerative Diseases; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Nervous System Malformations; Polyneuropathies; Hereditary Sensory and Motor Neuropathy; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Mobility Limitation; Charcot-Marie-Tooth Disease; Neuromuscular Diseases; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Therapeutics; Patient Care; Health Services; Health Care Facilities Workforce and Services; Aftercare; Continuity of Patient Care; Exercise; Rehabilitation
• Other Study ID Numbers: PekingUTH WZQ-CMT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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