Clinical trial NCT02421731: Robot-assisted Gait Training on Mobility in Severely Disabled Multiple Sclerosis Patients
Official title: Effectiveness of Robot-assisted Gait Training Versus Conventional Therapy on Mobility in Severely Disabled Multiple Sclerosis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Multiple Sclerosis
Keywords: Rehabilitation
Gait
Lead sponsor: University Hospital of Ferrara
Sponsor class: OTHER
Collaborators: name: Regione Emilia-Romagna
name: Università degli Studi di Ferrara
First posted: 2015-04-21
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Gait disabilities affect personal activities and quality of life of progressive multiple sclerosis (MS) patients. A robot-driven gait orthosis allowing a more effective support of walking movements and imitation of a nearly normal gait pattern during treadmill training at a higher speed has been developed and recently introduced in clinical settings. However, until now few studies evaluated the effects of Robot-Assisted Gait Training (RAGT) in a group of stroke, spinal cord injury and MS subjects.

In addition, the training-induced neural and biological changes potentially related to the mechanisms of recovery remain undefined.

The primary aims of this study are:

to test the feasibility of RAGT in a group of progressive severely disabled MS patients and to test the hypothesis that this intensive intervention could have higher benefit, compared with conventional therapy alone, in mobility improvement as assessed by the Timed 25 Foot Walk (T25FW)

The secondary aims of this study are:

to determine whether fatigue, Quality of life, balance and locomotor function are improved by RAGT; to determine whether gait training influences markers of plasticity including clinical and circulating biomarkers to search for a possible correlation between clinical outcomes and clinical and circulating biomarkers

Detailed description: This is a prospective, randomized, single-blinded, controlled study. Ninety-eight MS subjects will be recruited from the identification of subjects at U.O. Rehabilitative Medicine and Rare Diseases and Neuroimmune Center, IRCCS Neurosciences "Bellaria" (BO).

After evaluation of their eligibility and when obtained the informed consent, patients will be enrolled and randomized to the two groups through a randomization stratification approach. Subjects will be grouped into strata defined by the degree of impairment (e.g. using outcomes from the Expanded Disability Status Scale or EDSS) and then randomized separately within each stratum according to a block randomization and will be assigned to one of the two treatment groups:

1. robot-assisted gait training (experimental group)
2. conventional therapy (control group)

Robot-assisted gait training:

Patients will receive 12 training sessions over 4 weeks (3 sessions/week) of RAGT. During these sessions subjects will wear a harness attached to a system to provide body weight support and they will walk on a treadmill with the help of a robotic-driven gait orthosis. The legs are guided according to a physiological gait pattern. The torque of the knee and hip drives can be adjusted from 100% to 0% for one or both legs. The speed of the treadmill can be adjusted from 0 km/h to approximately 3 km/h and body weight support from 0% to 100%. During the first session we will set these training parameters according to subject characteristics and demand level. As training will progress, adjustments in the assistance provided by the driven-gait orthosis, the amount of body weight support and treadmill speed will be performed. Training sessions will last for an hour with 30 minutes of real walking time, because subject set-up in the device take approximately 30 minutes.

Conventional therapy:

The control group will receive 12 conventional therapy sessions over 4 weeks (3 sessions/week), that will focus on gait training. Subjects will receive 1 hour of individual conventional physiotherapy for session. During the first 5-10 minutes the subjects will perform lower-limb and core stretching exercises to increase muscles flexibility; then they'll deal with lower-limb muscles strengthening exercises tailored on their baseline characteristics (10 minutes). After that, assisted over-ground walking training will be performed.

Outcome measures Outcome measures will be assessed a week before the treatment initiation (T0), after two weeks (T1), after 4 weeks (T2) and at 3 months follow-up (T3). Personnel blinded to the treatment will assess the effects of the intervention.

Eligibility criteria: Inclusion Criteria:

* severe gait impairments defined as EDSS 6-7
* lack of EDSS worsening in the last 3 months

Exclusion Criteria:

* neurologic conditions in addition to MS that may affect motor function and other medical conditions likely to interfere with the ability to safely complete the study protocol
* impaired cognitive functioning: score less than 24 on the Mini Mental State Examination
* spasticity (Ashworth scale \>3) or contractures that may limit range of motion or function
* changes in disease modifying drug therapy or in any other confounding factor during the study.

Primary outcomes:
measure: Timed 25 Foot Walk
timeFrame: weeks: 0,2,4,16
Secondary outcomes:
measure: Six-Minute Walking Test
timeFrame: weeks: 0,2,4,16
measure: Berg Balance Scale
timeFrame: weeks: 0,2,4,16
measure: Up and Go Test
timeFrame: weeks: 0,2,4,16
measure: Fatigue Severity Scale
timeFrame: weeks: 0,2,4,16
measure: Modified Ashworth Scale
timeFrame: weeks: 0,2,4,16
measure: Short-Form 36
timeFrame: weeks: 0,2,4,16
measure: Haemodynamic measurements
timeFrame: weeks: 0,2,4,16
measure: Metabolic measurements by Near infrared spectroscopy
timeFrame: weeks: 0,2,4,16
measure: Circulating biomarkers
timeFrame: weeks: 0,2,4,16
Other outcomes:
Locations:
city: Ferrara
country: Italy
facility: Ferrara University Hospital
Study officials:
affiliation: Ferrara Rehabilitation Hospital
name: Sofia Straudi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Manfredini F, Straudi S, Lamberti N, Patergnani S, Tisato V, Secchiero P, Bernardi F, Ziliotto N, Marchetti G, Basaglia N, Bonora M, Pinton P. Rehabilitation Improves Mitochondrial Energetics in Progressive Multiple Sclerosis: The Significant Role of Robot-Assisted Gait Training and of the Personalized Intensity. Diagnostics (Basel). 2020 Oct 17;10(10):834. doi: 10.3390/diagnostics10100834.
citation: Straudi S, Manfredini F, Lamberti N, Martinuzzi C, Maietti E, Basaglia N. Robot-assisted gait training is not superior to intensive overground walking in multiple sclerosis with severe disability (the RAGTIME study): A randomized controlled trial. Mult Scler. 2020 May;26(6):716-724. doi: 10.1177/1352458519833901. Epub 2019 Mar 4.
citation: Straudi S, Manfredini F, Lamberti N, Zamboni P, Bernardi F, Marchetti G, Pinton P, Bonora M, Secchiero P, Tisato V, Volpato S, Basaglia N. The effectiveness of Robot-Assisted Gait Training versus conventional therapy on mobility in severely disabled progressIve MultiplE sclerosis patients (RAGTIME): study protocol for a randomized controlled trial. Trials. 2017 Feb 27;18(1):88. doi: 10.1186/s13063-017-1838-2.