Effects of Resistance Exercises in Hereditary Sensory-Motor Neuropathy (Charcot-Marie-Tooth Disease)

Effects of a Resistance Exercise Training Program on Skeletal Muscle Quality, Functional Capacity, and Quality of Life in Young Individuals With and Without Hereditary Sensorimotor Polyneuropathy

The goal of this clinical trial is to compare the effects of an 8-week resistance exercise training program on skeletal muscle quality, functional capacity, and quality of life in young individuals aged 15 to 29 years, with and without Hereditary Sensorimotor Polyneuropathy (HSPN).

The main questions to answer are:

What is the effect of an 8-week resistance exercise training program on skeletal muscle quality, functional capacity, and quality of life in young individuals with and without HSPN?

Will the percentage of improvement after the program be greater in participants with HSPN compared to those without, due to greater baseline alterations?

Researchers will compare the resistance exercise training program with baseline conditions to determine its effectiveness in improving skeletal muscle quality, functional capacity, and quality of life.

Participants will undergo a supervised lower-limb resistance exercise program (3x/week) for 8 weeks. The intervention will include progressive loads from 60% to 80% of 1-Repetition Maximum (1RM), with exercises targeting the major lower limb muscle groups. All participants will complete pre- and post-intervention evaluations, including ultrasound assessment of muscle architecture, functional capacity tests, strength measurements, body composition analysis, and quality of life questionnaires.

Introduction: Hereditary sensorimotor polyneuropathy (HSPN), also known as Charcot-Marie-Tooth disease (CMT), is the most prevalent group of hereditary neuromuscular disorders. It is characterized by muscle distal weakness, muscle atrophy, sensory loss, balance impairments, skeletal deformities and, in some cases, respiratory dysfunction. These impairments lead to reduced muscle quality, functional capacity, and quality of life. Muscle quality encompasses both morphological and functional aspects of skeletal muscle, including muscle architecture, composition, and strength.

Resistance exercise training (RET) has been shown to improve strength, muscle morphology, and functional performance in various populations. However, there is limited evidence on its effectiveness in individuals with HSPN, particularly in young adults. No studies to date have compared the effects of lower-limb-focused RET on muscle quality, functional capacity, and quality of life in young adults with and without HSPN.

Objectives:

The primary objetive of this study will be to assess the change in muscle thickness and echogenicity as markers of muscle quality, evaluated through ultrasonography in the tibialis anterior muscles of the lower limbs of participants undergoing 8 weeks of resistance training

Secondary objectives include:

• Characterize muscle architecture through ultrasonographic evaluation (fascicle length, pennation angle, and muscle thickness).
• Assessing changes in body composition.
• Evaluating muscle regeneration biomarkers.
• Determining the impact on respiratory muscle strength and aerobic capacity
• Evaluate maximal handgrip strength
• Assess overall lower-limb strength
• Assess overall upper-limb strength
• Measure maximal voluntary isometric strength
• Evaluate functional ankle muscle strength
• Determine maximal lower-limb muscle strength
• Assess balance and gait performance
• Evaluate health-related quality of life (HRQoL)
• Analyze body composition
• Investigate muscle regeneration
• Monitor physical activity levels

Materials and Methods: This clinical trial will recruit 22 participants (n=11 with HSPN, n=11 without HSPN), aged 15-29 years. Participants will be assigned to an 8-week supervised lower-limb RET program, performed 3 times per week, with progressive loads from 60% to 80% of one-repetition maximum (1RM). Exercises will target the major lower limb muscle groups and include leg press, knee extension, knee flexion, and ankle dorsiflexion.

Assessments will be conducted pre- and post-intervention, including:

• Muscle architecture and composition via ultrasound (tibialis anterior thickness, fascicle length, pennation angle, echogenicity).
• Muscle strength tests (isometric voluntary contraction, 1RM, grip strength).
• Functional capacity tests (6-minute walk test, balance assessment).
• Body composition (bioimpedance, anthropometry).
• Health-related quality of life (SF-36 questionnaire).
• Blood markers for muscle regeneration (creatine kinase). All participants will maintain habitual diet and physical activity levels during the intervention.

Expected Results: It is hypothesized that 8 weeks of progressive RET will result in greater improvements in muscle quality, functional capacity, and quality of life compared to baseline in both groups, with greater relative improvements expected in participants with HSPN due to lower baseline values. Increases in tibialis anterior thickness and reductions in echogenicity are expected, along with improvements in muscle strength, aerobic capacity, and balance. No serious adverse events are anticipated.

Inclusion Criteria:

• Men or women between 15 and 29 years of age with a diagnosis of hereditary sensorimotor polyneuropathy (HSPN) in any of its subtypes, living in the community (for experimental group).
• Healthy men or women between 15 and 29 years of age living in the community (for control group).
• Having active ankle movement within a range from plantarflexion to at least 0° of ankle dorsiflexion, allowing for strength training.

Exclusion Criteria:

• Osteoarticular or mobility impairments that prevent safe performance of resistance exercise training (e.g., ankle arthrodesis).
• Use of nutritional supplements that may affect skeletal muscle regulation (leucine, glutamine, casein, whey protein, fatty acids, creatine, among others).
• Untreated and/or uncontrolled chronic diseases or intellectual disability.
• History of surgery
• Participation in a resistance exercise training program within the past 6 months.