Abstract
BackgroundGait and mobility impairments affect the quality of life (QoL) of patients with progressive multiple sclerosis (MS). Robot-assisted gait training (RAGT) is an effective rehabilitative treatment but evidence of its superiority compared to other options is lacking. Furthermore, the response to rehabilitation is multidimensional, person-specific and possibly involves functional reorganization processes. The aims of this study are: (1) to test the effectiveness on gait speed, mobility, balance, fatigue and QoL of RAGT compared to conventional therapy (CT) in progressive MS and (2) to explore changes of clinical and circulating biomarkers of neural plasticity.MethodsThis will be a parallel-group, randomized controlled trial design with the assessor blinded to the group allocation of participants. Ninety-eight (49 per arm) progressive MS patients (EDSS scale 6–7) will be randomly assigned to receive twelve 2-h training sessions over a 4-week period (three sessions/week) of either: (1) RAGT intervention on a robotic-driven gait orthosis (Lokomat, Hocoma, Switzerland). The training parameters (torque of the knee and hip drives, treadmill speed, body weight support) are set during the first session and progressively adjusted during training progression or (2) individual conventional physiotherapy focusing on over-ground walking training performed with the habitual walking device. The same assessors will perform outcome measurements at four time points: baseline (before the first intervention session); intermediate (after six training sessions); end of treatment (after the completion of 12 sessions); and follow-up (after 3 months from the end of the training program). The primary outcome is gait speed, assessed by the Timed 25-Foot Walk Test. We will also assess walking endurance, balance, depression, fatigue and QoL as well as instrumental laboratory markers (muscle metabolism, cerebral venous hemodynamics, cortical activation) and circulating laboratory markers (rare circulating cell populations pro and anti-inflammatory cytokines/chemokines, growth factors, neurotrophic factors, coagulation factors, other plasma proteins suggested by transcriptomic analysis and metabolic parameters).DiscussionThe RAGT training is expected to improve mobility compared to the active control intervention in progressive MS. Unique to this study is the analysis of various potential markers of plasticity in relation with clinical outcomes.Trial registrationClinicalTrials.gov, identifier: NCT02421731. Registered on 19 January 2015 (retrospectively registered).
Highlights
Gait and mobility impairments affect the quality of life (QoL) of patients with progressive multiple sclerosis (MS)
Several studies have tested in samples of MS patients the effects of interventions, such as treadmill training [4], bodyweightsupported training on a treadmill [20, 21], Robot-assisted gait training (RAGT) [18, 19, 22,23,24,25,26], or both treatments combined within a single session [27], reporting small but positive effects on functional status [4, 18,19,20, 23,24,25,26] or QoL [10, 21]
We expect to observe a greater effect of high-intensive robotic rehabilitation on mobility and functional recovery in a large cohort of MS patients compared to conventional therapy (CT)
Summary
Study design and setting This study is a parallel-assignment, single-blinded, randomized controlled trial with the assessor blinded to the group allocation of participants (Fig. 1). Outcome assessment and data collection Outcome measurements will be evaluated at the Operative Unit of Physical and Rehabilitation Medicine of Ferrara University Hospital by the same blinded assessors at the four time points (Fig. 1): (a) baseline (prior to the first intervention session, T0), (b) intermediate (after six training sessions, T1), (c) end of treatment (after the completion of 12 sessions, T2) and (d) follow-up (after 3 months from the end of training program, T3). Patients enrolled in the study will undergo metabolic evaluation consisting of different measurements: assessment of muscular oxygen consumption at gastrocnemius at rest (rmVO2) and dynamic evaluation of cerebral activation during a simple walking task performed on a treadmill. Metabolic and laboratory-based measures will be performed according to the procedures detailed above Possible correlation between these factors and clinical measures will be assessed by Spearman’s rho or included in multiple regression models. The authors intend to spread the information learned from this project by presenting it at MS support groups, to inform the patients about the efficacy of one or the other treatment and the local availability of them
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