Clinical trial NCT06742697: Flexibility, Resistance, Aerobic, Movement Execution Training in Adults With Hereditary Spastic Paraplegia
Official title: Flexibility, Resistance, Aerobic, Movement Execution (FRAME) Training Program to Improve Gait Capacity in Adults With Hereditary Spastic Paraplegia: Protocol for a Single-cohort Feasibility Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Hereditary Spastic Paraplegia
Keywords: feasibility
gait
endurance
speed
balance
neurorehabilitation
hereditary spastic paraplegia
motor learning
aerobic exercise
high intensity interval training
resistance training
flexibility training
gait training
Lead sponsor: IRCCS Eugenio Medea
Sponsor class: OTHER
First posted: 2024-12-19
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single-cohort feasibility trial.
Primary purpose: TREATMENT

Brief summary: Hereditary Spastic Paraplegia (HSP) is a diverse group of genetic neurological conditions causing progressive weakness and spasticity in the lower limbs, severely reducing balance and gait capabilities. There is currently a lack of structured neurorehabilitation programs aimed at improving gait in adults with HSP. This protocol seeks to assess the feasibility and effectiveness of a structured training approach focusing on flexibility, muscle strength, motor control, balance, and aerobic capacity.

To this end, twenty adults diagnosed with HSP will engage in 10 to 16 sessions, each lasting 60 to 120 minutes, guided by a therapist once or twice a week, depending on individual preferences. At the end of the program, participants will receive a transfer package, including written instructions (a manual) and video tutorials, to encourage ongoing exercise at home. Assessments will occur before the intervention (T0), immediately after (T1), and three months later (T2). The primary outcomes will measure the feasibility of the program, including recruitment, retention, adherence, the absence of adverse events, and patient satisfaction. Secondary outcomes will focus on improvements in gait capabilities such as gait endurance and gait speed.

Detailed description: 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: 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: Therapeutic efficacy of the study, assessed by:

Improvement in walking endurance (6-Minute Walk Test). 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, non-randomized, uncontrolled interventional study.

STUDY POPULATION: Hereditary Spastic Paraplegia patients

SAMPLE SIZE: 20 patients

ELIGIBILITY:

Inclusion criteria:

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:

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.

Eligibility criteria: Inclusion Criteria:

* Adults diagnosed with Hereditary Spastic Paraplegia.
* Presence of any functional deficit in the lower limbs that affects walking, such as muscle weakness, hypertonia, or balance issues.
* Ability to walk without the need for physical contact with another person, as 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 and undergo at least 10 treatment sessions, eligible and willing to sign the informed consent.

Exclusion Criteria:

* Botulinum toxin or surgery to treat lower limb hypertonia in the six months prior to enrollment in the study.
* Contraindications for moderate physical activity, such as stretching exercises, muscle strength training, and aerobic capacity training.

Primary outcomes:
measure: Feasibility (recruitment rate).
timeFrame: Enrolment (T0), end of treatment five to ten weeks after T0 (T1).
measure: Feasibility (adherence rate).
timeFrame: Enrolment (T0), end of treatment five to ten weeks after T0 (T1).
measure: Feasibility (retention rate).
timeFrame: Enrolment (T0), end of treatment five to ten weeks after T0 (T1).
measure: Feasibility (safety).
timeFrame: Enrolment (T0), end of treatment five to ten weeks after T0 (T1).
Secondary outcomes:
measure: Six Minute Walking Test (6MWT).
timeFrame: Enrolment (T0), end of treatment five to ten weeks after T0 (T1), follow-up 12 weeks after T1 (T2).
measure: Ten Metre Walk Test (10MWT).
timeFrame: Enrolment (T0), end of treatment five to ten weeks after T0 (T1), follow-up 12 weeks after T1 (T2).
Other outcomes:
measure: Passive range of motion.
timeFrame: Enrolment (T0), end of treatment five to ten weeks after T0 (T1), follow-up 12 weeks after T1 (T2).
measure: Hereditary Spastic Paraplegia - Self Notion and Perception Questionnaire (HSP-SNAP).
timeFrame: Enrolment (T0), end of treatment five to ten weeks after T0 (T1), follow-up 12 weeks after T1 (T2).
measure: Functional Reach Test (FRT).
timeFrame: Enrolment (T0), end of treatment five to ten weeks after T0 (T1), follow-up 12 weeks after T1 (T2).
measure: Five times Sit-to-Stand (5TSTS).
timeFrame: Enrolment (T0), end of treatment five to ten weeks after T0 (T1), follow-up 12 weeks after T1 (T2).
measure: modified Spastic Paraplegia Rating Scale (mSPRS)
timeFrame: Enrolment (T0), end of treatment five to ten weeks after T0 (T1), follow-up 12 weeks after T1 (T2).
measure: Stabilometric platform.
timeFrame: Enrolment (T0), end of treatment five to ten weeks after T0 (T1), follow-up 12 weeks after T1 (T2).
measure: Isometric strength.
timeFrame: Enrolment (T0), end of treatment at four weeks (T1), follow-up at 12 weeks after T1 (T2).
Locations:
city: Bosisio Parini
country: Italy
facility: Scientific Institute, IRCCS E. Medea, Department of Bosisio Parini, Lecco, Italy.
state: Lombardia
city: Pieve di Soligo
country: Italy
facility: Scientific Institute, IRCCS E. Medea, Department of Pieve di Soligo, Treviso, Italy
state: Veneto
Study officials:
affiliation: Scientific Institute, IRCCS E. Medea, Department of Conegliano, Treviso, Italy.
name: Leonardo Boccuni, PhD
role: PRINCIPAL_INVESTIGATOR
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