NEUROMOdulation Pain Therapy in Combination With Intensive Physiotherapy (NEUROMOFY)

NEUROMOdulation Pain Therapy in Combination With Intensive Physiotherapy on a Neurophysiological Basis Improves Not Only Pain But Also Mobility in Spastic Paraparesis

In this project, the aim is to verify that neuromodulation therapy (spinal cord stimulation) in combination with intensive physiotherapy on a neurophysiological basis will lead to the restoration of mobility of lower limbs.

Study Overview

• Status: Not yet recruiting
• Conditions: Spinal Cord
• Intervention / Treatment: Procedure: NEUROMOdulation pain therapy in combination with intensive physiotherapy

Detailed Description

So far, posterior spinal cord neurostimulation (NM SCS) has been applied as a standard in patients with the most severe forms of pharmacoresistant neuropathic pain. The most recent research of the last 1-2 years brings clinical findings that, in a mode and modified arrangement, it could even induce rhythmic muscle activity of the lower limbs and help in verticalization and assisted bipedal locomotion.

In this project, the aim is to verify that neuromodulation therapy SCS (spinal cord stimulation) in combination with intensive physiotherapy on a neurophysiological basis will lead to the restoration of mobility of lower limbs.

In the therapy, the neuronal circuits of the lumbosacral region, where the so-called central pattern generators for locomotion are located will be targeted. Neurostimulation of this area will generate motor movement patterns corresponding to the previous mapping of the corresponding muscle groups. These will be supported by intensive physiotherapy on a neurophysiological basis - thanks to it and the facilitation of movement by neurostimulation, global motor patterns will be triggered, and motor programs stored at the subcortical level will be activated. Their memorization and subsequent spontaneous retrieval will facilitate sensorimotor learning techniques.

Current research further shows that neurostimulation stimulates neurons in Rexed laminae 3-5, specifically a group of neurons designated as SC VSX2 and subsequently proprioceptive fibres. Physiotherapy will enhance the effect of neuromodulation by stimulating proprioceptors using soft and neurophysiologically based techniques. Proprioceptive fibres make connections to motoneurons and also ascend through the spinal cord to the brain, and thus reflex motor movements can be triggered. Information about them is carried to the brain by ascending pathways, and thus a free awareness of the movement facilitated by the neurostimulator occurs. All these mechanisms should potentiate plasticity (and lead to the restoration of locomotion.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kamila Řasová, assoc. prof.; Phone Number: +420604511416; Email: kamila.rasova@lf3.cuni.cz

Study Locations

• Czechia
  • Prague, Czechia
    • Departmet of revmatology and rehabilitation, Faculty Thomayer Hospital
    • Contact: Tom Philipp, Ph.D.; Phone Number: +420737273589; Email: tom.philipp@ftn.cz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

spinal cord lesion

Exclusion Criteria:

other neurological conditions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: NEUROMOdulation pain therapy in combination with intensive physiotherapy; Neuromodulation therapy (low-voltage electrical stimulation of the posterior roots of the spinal cord) by electrodes inserted epidurally from a laminotomy in the lumbosacral region. Intensive, four hour per day, individual physiotherapy (soft techniques, methods based on neurophysiology, so-called neuroproprioceptive "facilitation, inhibition" (Vojta's reflex method, Motor programs activating therapy, Proprioceptive neuromuscular stimulation, Bobath concept) will be combined with methods of acquiring motor skills (individualized therapy using the knowledge of sensorimotor learning) will take minimally one month.

Procedure: NEUROMOdulation pain therapy in combination with intensive physiotherapy; Neuromodulation: Spinal cord stimulation affects nerve tissues with a defined electrical current. We will use low-voltage electrical stimulation of the posterior roots of the spinal cord in the MRI region of the localized conus medullaris. Electrodes are inserted epidurally from a laminotomy in the lumbosacral region. Physiotherapy will be based on recommendations for spinal patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Muscle strength at 2 weeks, 6 weeks, 6 and 12 months	Hip flexion, abduction and extension, knee flexion and extension, plantar flexion and dorsiflexion using a microFET2 digital dynamometer. The higher value, the better function (higher strength).	Pre-assessment (baseline testing), Post-assessment 1 (immediately after the end of two weeks hospitalisation), Post-assessment 2 (immediately after the end of one month hospitalisation), Follow up (6 and 12 month after beginning of the study).
Change in Spasticity at 2 weeks, 6 weeks, 6 and 12 months	Hip flexors, knee flexors and extensors, dorsal and plantar flexors using the Modified Ashworth scale. The higher value, the worse function (higher spasticity).	Post-assessment 1 (immediately after the end of two weeks hospitalisation)
Change from Baseline Timed Up And Go at 2 weeks, 6 weeks, 6 and 12 months	The subject stands up from a chair, walks 3m, turns back, and sits down again as quickly and safely as possible while being timed. Higher times reflect worse mobility.	Post-assessment 1 (immediately after the end of two weeks hospitalisation)
Change from Baseline Berg Balance Scale at 2 weeks, 6 weeks, 6 and 12 months	The subject stands up from a chair, walks 3m, turns back, and sits down again as quickly and safely as possible while being timed. Higher times reflect worse mobility.	Post-assessment 1 (immediately after the end of two weeks hospitalisation)
Change from Baseline The 10 Metre Walk Test at 2 weeks, 6 weeks, 6 and 12 months	A performance measure used to assess walking speed in meters per second over 10 meters. Shorter times reflect better mobility.	Post-assessment 1 (immediately after the end of two weeks hospitalisation)
Change from Baseline The 6 Minute Walk Test at 2 weeks, 6 weeks, 6 and 12 months	A long walking capacity test recording the maximal distance a subject walks at the fastest speed possible in 6 minutes. The more distance covered, the better the walking performance is.	Post-assessment 1 (immediately after the end of two weeks hospitalisation)
Change in Walking Index for Spinal Cord Injury at 2 weeks, 6 weeks, 6 and 12 months	questionnaire from 0 to 20. Higher number means better function.	Pre-assessment (baseline testing), Post-assessment 1 (immediately after the end of two weeks hospitalisation), Post-assessment 2 (immediately after the end of one month hospitalisation), Follow up (6 and 12 month after beginning of the study).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Visual Analogue Scale for pain at 2 weeks, 6 weeks, 6 and 12 months	scale from 0 to 10. Higher number means worse function (higher subjective feeling of pain)	Pre-assessment (baseline testing), Post-assessment 1 (immediately after the end of two weeks hospitalisation), Post-assessment 2 (immediately after the end of one month hospitalisation), Follow up (6 and 12 month after beginning of the study).
Change in The Fatigue Scale for Motor and Cognitive Functions at 2 weeks, 6 weeks, 6 and 12 months	Questionnaire with 20 questions on fatigue. Higher number, worse fatigue.	Pre-assessment (baseline testing), Post-assessment 1 (immediately after the end of two weeks hospitalisation), Post-assessment 2 (immediately after the end of one month hospitalisation), Follow up (6 and 12 month after beginning of the study).
Change in SYMBOL DIGIT MODALITIES TEST at 2 weeks, 6 weeks, 6 and 12 months	Cognitive testing (putting right symbols in 90 seconds). Higher number, better function.	Pre-assessment (baseline testing), Post-assessment 1 (immediately after the end of two weeks hospitalisation), Post-assessment 2 (immediately after the end of one month hospitalisation), Follow up (6 and 12 month after beginning of the study).
Change in European Health Questionnaire at 2 weeks, 6 weeks, 6 and 12 months	questionnaire on Quality of Life. Higher value, better quality of life.	Pre-assessment (baseline testing), Post-assessment 1 (immediately after the end of two weeks hospitalisation), Post-assessment 2 (immediately after the end of one month hospitalisation), Follow up (6 and 12 month after beginning of the study).
Change from Baseline World Health Organisation Disability Assessment Schedule 2.0 at 2 weeks, 6 weeks, 6 and 12 months	the 36-item questionnaire, higher score means higher disability	Pre-assessment (baseline testing), Post-assessment 1 (immediately after the end of two weeks hospitalisation), Post-assessment 2 (immediately after the end of one month hospitalisation), Follow up (6 and 12 month after beginning of the study).
Change in the 36-Item Short Form Survey Instrument at 2 weeks, 6 weeks, 6 and 12 months	36 item questionnaire. Higher number, worse quality of life.	Pre-assessment (baseline testing), Post-assessment 1 (immediately after the end of two weeks hospitalisation), Post-assessment 2 (immediately after the end of one month hospitalisation), Follow up (6 and 12 month after beginning of the study).
Change from Baseline Goal Attainment scale at 2 weeks, 6 weeks, 6 and 12 months	Each goal is rated on 5-point scale (-2 much less than expected, 0 achieved the expected level, 2 much more than expected). Higher score means a better outcome.	Pre-assessment (baseline testing), Post-assessment 1 (immediately after the end of two weeks hospitalisation), Post-assessment 2 (immediately after the end of one month hospitalisation), Follow up (6 and 12 month after beginning of the study).
Change in the Spinal Cord Independence Measure at 2 weeks, 6 weeks, 6 and 12 months	17 item questionnaire. Higher number, better function (lower independence).	Pre-assessment (baseline testing), Post-assessment 1 (immediately after the end of two weeks hospitalisation), Post-assessment 2 (immediately after the end of one month hospitalisation), Follow up (6 and 12 month after beginning of the study).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline the serum level of Long non-coding ribonucleic acid (lncRNA) at 2 weeks, 6 weeks, 6 and 12 months	LncRNAs are defined as RNA transcripts >200 nucleotides with limited coding potential, but multiple function of binding different DNA, mRNAs and proteins, and they can be expressed under different conditions. As an improvement will be interpreted a significant mean fold change in gene expression (≥ 2.0, p value ≤ 0.05) between two groups following endogenous gene standardisation and normalization through control adjustment to a value of 1.0.	Pre-assessment (baseline testing), Post-assessment 1 (immediately after the end of two weeks hospitalisation), Post-assessment 2 (immediately after the end of one month hospitalisation), Follow up (6 and 12 month after beginning of the study).
Change in pattern of brain activity at 6 and 12 months	fMRI will follow the changes in functional and structural brain connectivity. All fMRI examinations shall be performed in MR system Siemens Vida 3T located in IKEM using 64-channel RF head coil. Examination protocol will include not only essential structural imaging (3D SPACE FLAIR sequence with isotropic spatial resolution of 1 mm3), but also the measurement of functional connectivity using resting state fMRI and measurement of structural connectivity by means of the evaluation of spatial distribution of molecular diffusion (generalized DTI - diffusion tensor imaging, with 108 spatial directions and 3 b-factors allowing the reconstruction not only of fractional anisotropy but also the diffusion kurtosis imaging). The duration of the entire MR examination should not exceed 45 minutes. Extent activation, better value.	Pre-assessment (baseline testing), Post-assessment 1 (immediately after the end of two weeks hospitalisation), Follow up (6 and 12 month after beginning of the study).
Change in muscle activity	Needle electromyography. Higher value, higher function.	Pre-assessment (baseline testing), Post-assessment 1 (immediately after the end of two weeks hospitalisation), Follow up (6 and 12 month after beginning of the study).

Collaborators and Investigators

• Sponsor: Charles University, Czech Republic
• Investigators: Principal Investigator: Kamila Řasová, assoc. prof., Department of rehabilitation, Third Faculty of Medicine, Charles University

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2024
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): December 22, 2026

Study Registration Dates

• First Submitted: September 14, 2022
• First Submitted That Met QC Criteria: September 14, 2022
• First Posted (Actual): September 16, 2022

Study Record Updates

• Last Update Posted (Estimated): February 6, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: physiotherapy; spinal cord stimulation
• Other Study ID Numbers: 092022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

All data sharing terms and conditions and the nature of the relationship between the study and new user will be contained in a Data-sharing Agreement that will be issued and sighed before any data are handed out. The de-identification process for each patient is to ensure anonymization of individual patient's data, in order to be able to share IPD within the terms of participant's consent and ethics committee approval.

The study policy on sharing defines the terms of privileged use by the study team. The research team requires to be appropriately notified and acknowledged in publications and other outputs of the transferred data (or analyses conducted by the study on the new users' behalf). The Data-sharing agreement will comprehend arrangements for data destruction or secure archiving.

It is planned that the data will be placed into an online repository (to be specified later).

• IPD Sharing Time Frame: The IPD will be made available from 3-months months following the first publication of findings based on the data until 3 years following the first publication.
• IPD Sharing Access Criteria: The datasets will be prepared and might be reachable on a request. The study team formally reviews access requests for proposals. The data on an exclusive basis will be made available for third party use/ the new user, which can range from direct provision of data, data analysis collaboration, and/or scientific collaboration.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No