Early Symptoms in Multiple Sclerosis: an Investigation Using fMRI and Gait Analysis to Develop Personalized Balance Training for People With Low Disability

NCT07805733 | Not Yet Recruiting

• 1 other identifier: 538/SL/26
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background Many people with Multiple Sclerosis (MS) experience a hidden yet clinically significant symptom: impaired balance or a persistent feeling of instability, even during the early stages of the disease (Martin et al., 2006). Although these individuals may appear to walk normally, they often report feeling unsteady, avoiding crowded environments, or fearing falls. In some cases, however, balance deficits become overt and disabling, depending on the location and extent of lesions within the central nervous system. This heterogeneity complicates both the assessment and treatment of balance disorders in MS and highlights the need for personalized evaluation and rehabilitation strategies (Carpinella et al., 2022). Because early balance impairments are often subtle, they tend to be underestimated in clinical practice and may remain untreated for months or even years. This delay can negatively affect confidence, mobility, safety, and overall quality of life. The present project seeks to address this gap by promoting early identification and intervention before substantial disability develops. Project Objectives The objectives of this project are: To identify the mechanisms underlying early balance impairment in people with MS. To develop and evaluate an early intervention based on Vestibular Physical Therapy (VPT) that specifically targets sensory reweighting and visuo-vestibular integration. The rehabilitation program is designed to improve gaze stability and saccadic velocity, both of which are essential for maintaining postural control and dynamic balance. In addition, functional magnetic resonance imaging (fMRI) will be used to investigate the neurophysiological mechanisms underlying the intervention, providing insight into how the brain adapts to vestibular stimulation. If successful, this approach could enable clinicians to detect and treat balance impairments at an earlier stage, using objective and measurable changes in gait and brain function as biomarkers of rehabilitation efficacy. Methodology The study will recruit two groups of participants: Individuals diagnosed with Multiple Sclerosis (Thompson et al., 2018; Wallace et al., 2025) with mild disability (Expanded Disability Status Scale, EDSS ≤ 2.5) who report balance complaints. Healthy volunteers matched for age and sex. At baseline (T0), all participants will undergo a comprehensive assessment including: Structural and functional MRI with vestibular stimulation to investigate the integrity and functional organization of the vestibular network. Instrumented gait analysis using wearable inertial sensors (Castiglia et al., 2025). Validated clinical scales and questionnaires assessing objective balance performance, perceived stability, fear of falling, fall risk, and health-related quality of life. Participants with MS will then be randomly assigned to one of two groups: Intervention group: Participants will receive a structured Vestibular Physical Therapy (VPT) program consisting of 12 sessions (three sessions per week). Unlike conventional vestibular rehabilitation, this protocol specifically focuses on sensory reweighting and visuo-vestibular integration to enhance gaze stability, saccadic velocity, and postural control. Control group: Participants will continue receiving standard clinical care for MS without additional vestibular rehabilitation during the initial study phase. Following completion of the 12-session intervention, all participants will repeat the full assessment battery (T1) to evaluate changes in gait performance, balance, patient-reported outcomes, and brain function. After a 4-week washout period, a crossover design will be implemented, with participants switching to the alternate treatment arm for an additional 12-session period, followed by a final assessment (T2). Participants initially assigned to the control group will not require a washout period before crossing over to the intervention, as they will not have received VPT during the first phase of the study.

Conditions

Multiple Sclerosis

Keywords

Multiple Sclerosis; Vestibular Physical Therapy; Gait Analysis; fMRI

Outcome Measures

Primary Outcomes (1)

• Mini-BESTest

  is a 14-item scale (0-28) measures anticipatory postural adjustments, reactive control, sensory orientation and dynamic gait. It is validated and reliable in people with MS. Test-retest reliability is "good to excellent" in mild/moderate MS. Higher scores indicate better balance stability.

  Baseline (T0), after first intervention period (T1; 4 weeks), and after crossover (T2; 8 weeks).

Secondary Outcomes (7)

• Neuroimaging (MRI)

  Baseline (T0), after first intervention period (T1; 4 weeks), and after crossover (T2; 8 weeks).

• Berg Balance Scale (BBS)

  Baseline (T0), after first intervention period (T1; 4 weeks), and after crossover (T2; 8 weeks).

• Dizziness Handicap Inventory (DHI)

  Baseline (T0), after the first intervention period (T1; 4 weeks), and after the crossover intervention (T2; 8 weeks).

• Activities-specific Balance Confidence (ABC) Scale

  Baseline (T0), after the first intervention period (T1; 4 weeks), and after the crossover intervention (T2; 8 weeks).

• Fatigue Severity Scale

  Baseline (T0), after the first intervention period (T1; 4 weeks), and after the crossover intervention (T2; 8 weeks).

Study Arms (3)

VPT

EXPERIMENTAL

People in this arm will be treated with a vestibular physical therapy programme.

Other: Vestibular Physical Therapy

No VPT

NO INTERVENTION

People in this arm will receive a no-add-on-intervention period

Healty control

NO INTERVENTION

A healthy control group is required to enable comparisons between individuals with MS and healthy participants.

Interventions

Vestibular Physical Therapy OTHER

Vestibular Physical Therapy sessions realized focusing on visuo-vestibular interaction (12 session, 3 x 4 weeks)

VPT

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• people with Relapsing-Remitting Multiple Sclerosis;
• All participants must be ambulatorial (EDSS ≤2.5);

You may not qualify if:

• relapse or medication changes in the prior 6 months;
• people with peripheral vestibular disorders;
• people with contraindications to MRI.
• We will also recruit 30 healthy volunteers, matched for age and sex, who will complete the assessment protocol once, to serve as a comparison group for individuals with MS.

Sponsors & Collaborators

• LIFE - Research and Care Institute - Santa Lucia IRCCS: lead

Related Publications (3)

• Tramontano M, Paolocci G, Piatti D, Attanasio G, Casagrande Conti L, Bergamini E, Manzari L, Lacquaniti F, Staab JP, Bosco G, Indovina I. Dynamic postural stability, symmetry, and smoothness of gait in patients with persistent postural-perceptual dizziness. J Vestib Res. 2025 Mar;35(2):82-90. doi: 10.1177/09574271241295615. Epub 2024 Nov 6.

  PMID: 39973598 BACKGROUND

• Piatti D, Paolocci G, Verdecchia DH, Grasso MG, Bosco G, Indovina I, Tramontano M. Effectiveness of vestibular physical therapy on balance and dizziness in people with multiple sclerosis: A systematic review and meta-analysis. J Vestib Res. 2026 May 5:9574271261444952. doi: 10.1177/09574271261444952. Online ahead of print.

  PMID: 42084487 BACKGROUND

• Caronni A, Gervasoni E, Ferrarin M, Anastasi D, Brichetto G, Confalonieri P, Di Giovanni R, Prosperini L, Tacchino A, Solaro C, Rovaris M, Cattaneo D, Carpinella I. Local Dynamic Stability of Gait in People With Early Multiple Sclerosis and No-to-Mild Neurological Impairment. IEEE Trans Neural Syst Rehabil Eng. 2020 Jun;28(6):1389-1396. doi: 10.1109/TNSRE.2020.2991636. Epub 2020 Apr 30.

  PMID: 32356754 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Maria Grazia Grasso, MD, PhD

  LIFE - Research and Care Institute - Santa Lucia IRCCS

  PRINCIPAL INVESTIGATOR

• Diego Piatti, PT, MSc

  LIFE - Research and Care Institute - Santa Lucia IRCCS

  STUDY DIRECTOR

• Iole Indovina, PhD

  LIFE - Research and Care Institute - Santa Lucia IRCCS

  STUDY CHAIR

• Gianfranco Bosco, MD, PhD

  LIFE - Research and Care Institute - Santa Lucia IRCCS

  STUDY CHAIR

• Giorgia Presicce, MD, PhD

  LIFE - Research and Care Institute - Santa Lucia IRCCS

  STUDY CHAIR

• Gianluca Paolocci, PhD

  LIFE - Research and Care Institute - Santa Lucia IRCCS

  STUDY CHAIR

• Marco Tramontano, PhD

  University of Bologna

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2026
• First Posted: September 4, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2029
• Last Updated: September 4, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share