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

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.

• Changes in muscle architecture through ultrasonographic evaluation (fascicle length and pennation angle) [Срок оценки: The evaluation will be conducted twice, before and after the 8-week intervention: the first, 2 days after signing the informed consent, and the second, 2 days after completing the treatment.]
• Serum creatine kinase concentration as a biomarker of muscle quality. [Срок оценки: The evaluation will be conducted twice, before and after the 8-week intervention: the first, 2 days after signing the informed consent, and the second, 2 days after completing the treatment.]
• Changes in total body mass [Срок оценки: The evaluation will be conducted twice, before and after the 8-week intervention: the first, 4 days after signing the informed consent, and the second, 4 days after completing the treatment.]
• Variation in anthropometric measurements [Срок оценки: The evaluation will be conducted twice, before and after the 8-week intervention: the first, 4 days after signing the informed consent, and the second, 4 days after completing the treatment.]
• Changes in aerobic capacity [Срок оценки: The evaluation will be conducted twice, before and after the 8-week intervention: the first, 4 days after signing the informed consent, and the second, 4days after completing the treatment.]
• Changes in respiratory muscle strength [Срок оценки: The evaluation will be conducted twice, before and after the 8-week intervention: the first, 4 days after signing the informed consent, and the second, 4 days after completing the treatment.]
• Changes in maximal handgrip strength [Срок оценки: The evaluation will be conducted twice, before and after the 8-week intervention: the first, 2 days after signing the informed consent, and the second, 2 days after completing the treatment.]
• Changes in overall lower-limb strength [Срок оценки: The evaluation will be conducted twice, before and after the 8-week intervention: the first, 2 days after signing the informed consent, and the second, 2 days after completing the treatment.]
• Changes in overall upper-limb strength [Срок оценки: The evaluation will be conducted twice, before and after the 8-week intervention: the first, 2 days after signing the informed consent, and the second, 2 days after completing the treatment.]
• Changes in maximal voluntary isometric strength [Срок оценки: The evaluation will be conducted twice, before and after the 8-week intervention: the first, 2 days after signing the informed consent, and the second, 2 days after completing the treatment.]
• Changes in functional ankle muscle strength [Срок оценки: The evaluation will be conducted twice, before and after the 8-week intervention: the first, 2 days after signing the informed consent, and the second, 2 days after completing the treatment.]
• Changes maximal lower-limb muscle strength [Срок оценки: The evaluation will be conducted twice, before and after the 8-week intervention: the first, 2 days after signing the informed consent, and the second, 2 days after completing the treatment.]