Traditional Versus Progressive Robot-assisted Gait Training in People With Multiple Sclerosis and Severe Gait Disability

Multiple Sclerosis Clinical Trial

— PROGR-EX  

Official title:

Traditional Versus Progressive Robot-assisted Gait Training in People With Multiple Sclerosis and Severe Gait Disability: Study Protocol for a the PROGR-EX Randomized-controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06381440
• Other study ID #: PROGR-EX_MNESYS
• Status: Recruiting
• Phase: N/A
• Start date: November 15, 2023
• Est. completion date: November 30, 2024

Study information

• Verified date: January 2024
• Source: University Hospital of Ferrara
• Contact: Sofia Straudi, PhD
• Phone: 0532238720
• Email: sofia.straudi[@]unife.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Multiple sclerosis (MS) is a demyelinating neurodegenerative disease. Qualitative alterations in walking function in MS people involve 75% of subjects with MS and are determined by reduced coordination, mobility, balance, and increased risk of falling. Robot assisted gait training (RAGT) devices seem effective in MS patients with severe motor disabilities, failing to show significant superiority when compared to intensive overground gait rehabilitation (OGT). This study aims to evaluate the effects of a low-intensity RAGT at progressively increasing intensity compared to conventional RAGT and OGT.

Description:

Gait disorders are the most frequent symptoms associated to multiple sclerosis (MS).Robot-assisted gait training (RAGT) in people with MS (PwMS) has been proposed as a possible effective treatment option for severe motor disability. Although RAGT continues to prove effective in increasing patient mobility, no significant superiority was found when compared to intensive overground gait rehabilitation (OGT). In PwMS, RAGT at high-intensity may enhance fatigue and spasticity, compromising the effectiveness and applicability of the intervention.

This study aims to evaluate the effects of a low-intensity RAGT at progressively increasing intensity compared to conventional RAGT and OGT in PwMS and moderate to severe walking impairment.

We will recruit 24 PwMS from the patients afferent to Outpatient Rehabilitation Clinic at University Hospital of Ferrara and we will assign them to one of the three treatment groups: low-intensity RAGT at progressively increasing intensity, conventional RAGT and OGT. All participants will receive 3 weekly treatment sessions of 3 hours each for 4 weeks. In the first 2 hours of treatment, an experienced physiotherapist will propose a programme based on stretching exercises, muscle strengthening and educational interventions. During the last hour, subjects will undergo specific gait training according to the assignment group. Subjects allocated to low-intensity RAGT at progressively increasing intensity group will receive gait rehabilitation on the Lokomat device and a speed initially set at 1.0 km/h, with progressive increments of 0.1 km/h at each training session. The working time consists of bouts of 3 minutes of work alternated by 1 minute of recovery, to be repeated 8 times. Subjects allocated to conventional RAGT will receive gait rehabilitation on the Lokomat device and the machine parameters will be determined based on the patient's characteristics. Subjects allocated to OGT will perform a 40-minute walk on a flat surface supervised by a physiotherapist. Outcomes will be assessed before and after treatment and at 3-month follow-up. The primary outcome is walking speed. Secondary outcomes include mobility and balance, psychological measures, muscle oxygen consumption, electrical and hemodynamic brain activity, urinary biomarkers, usability, and acceptability of robotic devices for motor rehabilitation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: November 30, 2024
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Diagnosis of MS (primary or secondary progressive) without relapses in the preceding 3 months

• Disability rate defined by Expanded Disability Status Scale (EDSS) score from 6 to 7

• Ability to perform the Timed 25-Foot Walk (T25-FW) test

• Mini-Mental Status Examination score = 24/30

Exclusion Criteria:

• Other (neurological) conditions that may affect motor function

• Medical conditions might interfere with the ability to complete the study protocol safely

• Presence of spasticity with a Modified Ashworth Scale (MAS) score > 3 or retractions limiting the range of motion of the hip, knee or ankle

• MS relapses or medication changes or any other confounding factors during the study period

• Rehabilitation treatment or botulinum toxin injection in the 3 months preceding the start of the study

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Device:
• Lokomat device (Hocoma AG, Volketswil, Switzerland).
Robot Assisted Gait Training device

Other:
• Conventional walking training
Self-paced supervised walking training

Locations

Country	Name	City	State
Italy	Department of Neuroscience and Rehabilitation, University Hospital of Ferrara	Ferrara	Emilia Romagna

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital of Ferrara	Università degli Studi di Ferrara, Universita di Verona

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Walking function	The walking function will be assessed by the T25-FW test	Score changes before (T0) and after (T1) the twelve sessions of treatment and at 3-months follow-up (T2).
Secondary	Mobility	Timed Up and Go (TUG) test	Score changes before (T0) and after (T1) the twelve sessions of treatment and at 3-months follow-up (T2).
Secondary	Walking endurance	6-Minute Walk Test (6MWT)	Score changes before (T0) and after (T1) the twelve sessions of treatment and at 3-months follow-up (T2).
Secondary	Balance	Berg Balance Scale (BBS), a 5-point ordinal scale used to assess the ability to maintain balance statically and while performing functional movements. BBS comprises 14 tasks; the total score is calculated by summing the scores of each item (0-4). The maximum total score is 56. Higher totals reflect more balance impairment.	Score changes before (T0) and after (T1) the twelve sessions of treatment and at 3-months follow-up (T2).
Secondary	Spasticity	Modified Ashworth Scale (MAS), a 6-point measure of spasticity. The assessor will rate the perceived amount of resistance or tone at the flexor and extensor muscles of the hip, knee, and ankle. Higher scores reflect more spasticity	Score changes before (T0) and after (T1) the twelve sessions of treatment and at 3-months follow-up (T2).
Secondary	Perceived quality of life	Multiple Sclerosis Impact Scale-29 (MSIS-29), a questionnaire that evaluates the impact of MS on physical and psychological functioning. It comprises 29 items, with 20 items assessing physical activity and 9 assessing psychological state. Each item can be rated from 0 to 5; the total score is the sum of all items. Higher score reflect higher impact of MS on quality of life.	Score changes before (T0) and after (T1) the twelve sessions of treatment and at 3-months follow-up (T2).
Secondary	Perceived walking ability	Multiple Sclerosis Walking Scale-12 (MSWS-12), a questionnaire used to evaluate the impact of MS on walking ability. It comprises 12 items that inquire about the patient's perception of gait speed, running, confidence in ascending/descending stairs, balance, and fatigue. The total score is calculated by summing the scores of each item (0-5) and then converting it into a value ranging from 0 to 100. Higher score reflect higher impact of MS on walking ability.	Score changes before (T0) and after (T1) the twelve sessions of treatment and at 3-months follow-up (T2).
Secondary	Fatigue	Fatigue Severity Scale (FSS), a short questionnaire that requires the subject to rate their level of fatigue from 1 to 7 in different activities. Higher score reflect higher impact of fatigue	Score changes before (T0) and after (T1) the twelve sessions of treatment and at 3-months follow-up (T2).
Secondary	Anxiety	Beck Anxiety Inventory (BAI), a questionnaire used to measure anxiety levels, consisting of 21 items. Respondents indicate how severely each symptom affected them using a 4-point Likert scale, ranging from 0 (not at all) to 3 (severely). The sum of all responses provides an overall score, with higher totals reflecting more intense anxiety symptoms	Score changes before (T0) and after (T1) the twelve sessions of treatment and at 3-months follow-up (T2).
Secondary	Depression	Beck Depression Inventory - II (BDI-II), a questionnaire comprised of 21 multiple-choice questions. Respondents assign a score ranging from 0 to 3 to each answer, where higher cumulative scores signal a greater severity of depressive symptoms	Score changes before (T0) and after (T1) the twelve sessions of treatment and at 3-months follow-up (T2).
Secondary	Kinesiophobia	Tampa Scale of Kinesiophobia (TSK), a 17-item self-evaluation checklist on a 4-point Likert scale to assess the fear of movement or potential re-injury. The scoring yields a total raw score that can range from 17 to 68 and higher cumulative scores reflect higher fear of movement.	Score changes before (T0) and after (T1) the twelve sessions of treatment and at 3-months follow-up (T2).
Secondary	Adaptation to medical condition	Psychosocial Adjustment to Illness Scale-Self Report (PAIS-SR), a 46-item self-report tool designed to evaluate a patient's adaptation to either a current medical condition or the aftermath of a past illness. Each question within the PAIS-SR is scored on a scale from 0 to 3, where a higher score reflects a lower level of adjustment	Score changes before (T0) and after (T1) the twelve sessions of treatment and at 3-months follow-up (T2).
Secondary	Coping strategies	Brief COPE, a self-report questionnaire used to evaluate coping strategies in facing stressful, unpredictable, and damaging events. It comprises 28 items grouped in 14 faced-scales which represent 14 different coping reactions. Respondents rate each item on a 4-point Likert scale, ranging from 1 (I haven't been doing this at all) to 4 (I've been doing this a lot). Total scores on each scale range from 2 (minimum) to 8 (maximum). Higher scores indicate increased utilization of that specific coping strategy.	Score changes before (T0) and after (T1) the twelve sessions of treatment and at 3-months follow-up (T2).
Secondary	Muscle oxygen consumption	The Near-infrared spectroscopy (NIRS) technology will evaluate muscle oxygen consumption. The patient, lying supine, will be fitted with a pair of NIRS sensors (transmitter and receiver) at the medial belly of the gastrocnemius to monitor changes in oxygenated and deoxygenated hemoglobin.	Data changes before (T0) and after (T1) the twelve sessions of treatment and at 3-months follow-up (T2).
Secondary	Hemodynamic cortical activation	Hemodynamic cortical activation recorded during reaching and grasping activities performed with the most impaired (or not dominant) upper limb. Each patient will be equipped with a Near-infrared spectroscopy (NIRS) system composed of 16 sources and 16 detectors emitting two wavelengths of near-infrared light (760 and 850 nm). Hemodynamic signals will be recorded at a sampling rate of 3.81 Hz. A standard cap will be placed over each participant's scalp, and sources and detectors were positioned on the measuring cap according to the 10-20 international system with standard interoptode distances of approximately 3 cm. Optodes were placed over both hemispheres, resulting in 48 channels covering the regions of the primary motor and sensorimotor cortices. Data will be analyzed assessing the variations in oxygenated and deoxygenated hemoglobin	Data changes before (T0) and after (T1) the twelve sessions of treatment and at 3-months follow-up (T2).
Secondary	Electrical brain activity	EEG recording during action observation task. Stimuli will consist in videos, filmed in the first person, in which a hand will show reaching for and grasping a can. The EEG will be recorded during the 20 minutes of the session: 3 minutes with open eyes, 3 minutes with closed eyes, and 14 minutes of video observation.	Data changes before (T0) and after (T1) the twelve sessions of treatment and at 3-months follow-up (T2).
Secondary	miRNA expression	Urinary lab examination	Data changes before (T0) and after (T1) the twelve sessions of treatment.
Secondary	Acceptability of robot intervention	Ad-hoc questionnaire with closed 1-10 Likert-scale and open-ended questions to assess patients' experience with the robot intervention. The questionnaire will specifically explore the usability, acceptability, perceived pleasantness, and safety of the intervention. Higher scores reflects higher satisfaction of the treatment.	Scores registered after (T1) the twelve sessions of robotic treatment.