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

NCT ID: NCT06742697

Last Updated: 2025-01-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-12-23

Study Completion Date

2027-04-30

Brief Summary

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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

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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.

Conditions

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Hereditary Spastic Paraplegia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Single-cohort feasibility trial.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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HSP Cohort

The whole cohort of HSP patients will receive the same comprehensive neurorehabilitation program aiming at improving gait capabilities (speed and endurance). The content and the dosis of the treatment will be personalized according to patient's specific needs and preferences.

Group Type EXPERIMENTAL

Flexibility, Resistance, Aerobic, Movement Execution training

Intervention Type BEHAVIORAL

Flexibility: static and dynamic stretching combined with sensory, high-frequency electrical stimulation to reduce spasticity and improve mobility.

Resistance training: core stability and lower limb strength training in conditions of instability, to improve strength, coordination, and balance.

Movement execution training: gait training according to motor learning principles.

Aerobic exercise: in the form of high-intensity interval training at the end of each session, to improve cardiovascular status and foster motor learning consolidation (probably due to the release of brain derived neurothrophic factors).

Interventions

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Flexibility, Resistance, Aerobic, Movement Execution training

Flexibility: static and dynamic stretching combined with sensory, high-frequency electrical stimulation to reduce spasticity and improve mobility.

Resistance training: core stability and lower limb strength training in conditions of instability, to improve strength, coordination, and balance.

Movement execution training: gait training according to motor learning principles.

Aerobic exercise: in the form of high-intensity interval training at the end of each session, to improve cardiovascular status and foster motor learning consolidation (probably due to the release of brain derived neurothrophic factors).

Intervention Type BEHAVIORAL

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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IRCCS Eugenio Medea

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Leonardo Boccuni, PhD

Role: PRINCIPAL_INVESTIGATOR

Scientific Institute, IRCCS E. Medea, Department of Conegliano, Treviso, Italy.

Locations

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Scientific Institute, IRCCS E. Medea, Department of Bosisio Parini, Lecco, Italy.

Bosisio Parini, Lombardy, Italy

Site Status RECRUITING

Scientific Institute, IRCCS E. Medea, Department of Pieve di Soligo, Treviso, Italy

Pieve di Soligo, Veneto, Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Leonardo Boccuni, PhD

Role: CONTACT

003904384141

Marco Bortolini, BSc

Role: CONTACT

003904389062

Facility Contacts

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Eleonora Diella, BSc

Role: primary

0039031877589

Leonardo Boccuni, PhD

Role: backup

003904384141

Leonardo Boccuni, PhD

Role: primary

003904384141

Marco Bortolini, BSc

Role: backup

003904389062

References

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Eng JJ, Tang PF. Gait training strategies to optimize walking ability in people with stroke: a synthesis of the evidence. Expert Rev Neurother. 2007 Oct;7(10):1417-36. doi: 10.1586/14737175.7.10.1417.

Reference Type BACKGROUND
PMID: 17939776 (View on PubMed)

Crozier J, Roig M, Eng JJ, MacKay-Lyons M, Fung J, Ploughman M, Bailey DM, Sweet SN, Giacomantonio N, Thiel A, Trivino M, Tang A. High-Intensity Interval Training After Stroke: An Opportunity to Promote Functional Recovery, Cardiovascular Health, and Neuroplasticity. Neurorehabil Neural Repair. 2018 Jun;32(6-7):543-556. doi: 10.1177/1545968318766663. Epub 2018 Apr 20.

Reference Type BACKGROUND
PMID: 29676956 (View on PubMed)

Thijs L, Voets E, Denissen S, Mehrholz J, Elsner B, Lemmens R, Verheyden GS. Trunk training following stroke. Cochrane Database Syst Rev. 2023 Mar 2;3(3):CD013712. doi: 10.1002/14651858.CD013712.pub2.

Reference Type BACKGROUND
PMID: 36864008 (View on PubMed)

Maccora S, Torrente A, Di Stefano V, Lupica A, Iacono S, Pilati L, Pignolo A, Brighina F. Non-pharmacological treatment of hereditary spastic paraplegia: a systematic review. Neurol Sci. 2024 Mar;45(3):963-976. doi: 10.1007/s10072-023-07200-1. Epub 2023 Nov 16. No abstract available.

Reference Type BACKGROUND
PMID: 37968432 (View on PubMed)

Bellofatto M, De Michele G, Iovino A, Filla A, Santorelli FM. Management of Hereditary Spastic Paraplegia: A Systematic Review of the Literature. Front Neurol. 2019 Jan 22;10:3. doi: 10.3389/fneur.2019.00003. eCollection 2019.

Reference Type BACKGROUND
PMID: 30723448 (View on PubMed)

Ruano L, Melo C, Silva MC, Coutinho P. The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology. 2014;42(3):174-83. doi: 10.1159/000358801. Epub 2014 Mar 5.

Reference Type BACKGROUND
PMID: 24603320 (View on PubMed)

Boccuni L, Bortolini M, Stefan C, Dal Molin V, Dalla Valle G, Martinuzzi A. 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. Front Neurol. 2025 Feb 18;16:1441512. doi: 10.3389/fneur.2025.1441512. eCollection 2025.

Reference Type DERIVED
PMID: 40040914 (View on PubMed)

Other Identifiers

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1130

Identifier Type: -

Identifier Source: org_study_id

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