Flexibility, Resistance, Aerobic, Movement Execution Training in Adults With Hereditary Spastic Paraplegia

INTRODUCTION: Hereditary Spastic Paraplegia (HSP) is a heterogeneous group of inherited neurological disorders characterized by progressive weakness and spasticity in the lower limbs, which significantly impairs walking abilities (endurance and speed). Despite several specific interventions for particular deficits already having been studied, there is currently a lack of comprehensive and structured neurorehabilitation programs designed to improve walking function in these patients. Therefore, this protocol aims to explore the feasibility and effectiveness of a composite training approach focused on improving flexibility, muscle strength, motor control, balance, and aerobic capacity. STUDY OBJECTIVES: Primary endpoint?Primary endpoint The main result the study is designed to measure and report on. Other results, called secondary outcomes, are also collected.: Feasibility of the study, assessed by the following: Sufficient recruitment rate, with 20 patients enrolled within 24 months from the study's initiation. Adequate adherence to the treatment plan, defined by the completion of at least 75% of the planned treatment sessions, with a minimum of 10 treatment sessions. Sufficient patient retention, defined as at least 75% of enrolled patients completing the study with adequate treatment adherence. Absence of serious adverse events related to patient participation in the study. Patient satisfaction with the healthcare received during the study. Secondary endpoint?Secondary endpoint An additional result the study measures alongside the primary outcome, for example quality of life or a laboratory value.: Therapeutic efficacy of the study, assessed by: Improvement in walking endurance (6-Minute Walk Test?6-Minute Walk Test A test of how far a person can walk on a flat surface in six minutes. It is used to measure stamina and to track change over time.). Improvement in walking speed (10-Meter Walk Test). Exploratory objectives: Improvement in overall functional condition (Spastic Paraplegia Rating Scale and the Hereditary Spastic Paraplegia - Self Notion and Perception Questionnaire). Improvement in passive joint range of motion in the lower limbs (goniometer). Improvement in lower limb muscle strength (5 Times Sit-to-Stand Test). Improvement in standing balance (Functional Reach Test and stabilometric platform). STUDY DESIGN: Open-label?Open-label No masking is used, so the assigned intervention is not deliberately hidden from participants or study staff., non-randomized?randomized Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable., uncontrolled interventional study?interventional study A study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.. STUDY POPULATION: Hereditary Spastic Paraplegia patients SAMPLE SIZE: 20 patients ELIGIBILITY: Inclusion criteria?Inclusion criteria The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.: Adults diagnosed with Hereditary Spastic Paraplegia. Presence of any functional deficit in the lower limbs affecting walking, such as muscle weakness, hypertonia, or balance issues. Ability to walk independently, without physical assistance from another person, defined by a Functional Ambulation Category score of 3 or higher. Ability to understand simple instructions, comprehend the purpose of the study, willingness to participate, commitment to at least 10 treatment sessions, and suitability for signing the informed consent. Exclusion criteria?Exclusion criteria The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.: Use of botulinum toxin or surgery to treat lower limb hypertonia within six months prior to study enrollment. Contraindications for moderate physical activity, including stretching exercises, muscle strengthening, and aerobic training. Withdrawal Criteria: Voluntary withdrawal by the patient. Occurrence of adverse events or health issues that prevent continuation of the treatment plan. Patient Replacement: Recruitment will continue until 20 subjects are enrolled. Any patients who withdraw from the study will not be replaced. METHODS: Twenty adults diagnosed with HSP will participate in 10 to 16 therapist-guided sessions, each lasting 60 or 120 minutes, occurring once or twice a week depending on individual choice and capabilities. At the conclusion of the study, participants will receive an information package (manual and video tutorials) to support long-term home exercise. Evaluations will take place at three time points: before the intervention (T0), immediately after the intervention (T1), and three months post-intervention (T2). The primary objectives will focus on assessing the study's feasibility (recruitment, retention, adherence, absence of adverse events, and patient satisfaction). Secondary outcomes will evaluate improvements in walking ability and specific contributing factors, such as reduced spasticity, increased muscle strength, and improved balance. INTERVENTION: FRAME training is composed of four key components: Component 1: Flexibility. To decrease muscle tone and enhance mobility, the therapist will apply a combination of stretching exercises and electrical stimulation, targeting areas such as the triceps surae, adductors, rectus femoris, and hamstrings. Electrical stimulation will utilize biphasic, high-frequency sensory stimulation (100 Hertz, pulse width 200 µs, and intensity just below the motor threshold) for a duration of 30 minutes, combined with stretching activities. Component 2: Resistance Training (and Balance). The resistance training will focus on strengthening muscles typically weakened in individuals with Hereditary Spastic Paraplegia (HSP), especially the proximal muscles of the hip and trunk. To promote muscle engagement and improve balance and coordination, core stability and resistance exercises will be performed under conditions of mild instability. These exercises will be carried out in sitting or standing positions, rather than lying down, to optimize muscle activation. Component 3: Movement Execution (and Balance). Gait training will be based on motor learning principles such as repetitive, task-oriented practice, variable practice, and graded practice. Graded practice involves breaking down a complex movement into simpler segments, practicing each segment until proficiency is achieved, and then progressively combining them into more complex sequences. Patients will be challenged with standing balance exercises while working on specific gait impairments. Gait training will involve varying walking patterns, including fast, slow, sidewalk walking, walking backward, and stair climbing. Component 4: Aerobic Training via High-Intensity Interval Training (HIIT). HIIT consists of brief, intense aerobic efforts using large muscle groups, followed by rest periods of equal length. HIIT has been found to produce better cardiovascular results with a lower perceived level of effort compared to moderate-intensity aerobic exercise. In this protocol, patients will perform 30-second high-intensity intervals followed by 30 seconds of passive rest, repeated 10 times in two sets. Each session will begin with a 5-minute warm-up, include a 5-minute rest between sets, and conclude with a 5-minute cool-down. Patients will participate in the modality most suitable for consistent training, such as walking, running, cycling, or squatting. RELEVANCE: This protocol is significant for providing clinicians with valuable insights into the feasibility and potential effectiveness of a comprehensive, clinically-oriented program designed to improve walking ability in adults with Hereditary Spastic Paraplegia. It also aims to inform future translational research studies in the field.