Functional and Structural Changes in the Central Nervous System Following Spinal Cord Injury

Spinal Cord Injuries Clinical Trial

Official title:

Functional and Structural Changes in the Central Nervous System Following Spinal Cord Injury

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05681936
• Other study ID #: 2022-00558
• Status: Recruiting
• Start date: January 1, 2023
• Est. completion date: August 31, 2027

Study information

• Verified date: August 2023
• Source: University of Zurich
• Contact: Gergely David, Dr.
• Phone: +41 44 510 72 13
• Email: gergely.david[@]balgrist.ch
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Building on recent improvements, state-of-the-art functional MRI will be applied as an advanced diagnostic tool for the lumbosacral cord in spinal cord injury (SCI) patients to characterize the remaining neuronal activity of the motor and sensory neurons. Alterations in the activity pattern will reveal the effect upon task-related spinal cord activity of the lower motor neurons and sensory neurons undergoing trauma-induced neurodegeneration, at a spatial specificity that has not been possible so far. Results of this study will be of crucial importance because SCI patients can only profit from regeneration-inducing therapies if spinal neuronal function is preserved below the level of lesion.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 225
• Est. completion date: August 31, 2027
• Est. primary completion date: August 31, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age > 18 years

• Informed consent

• Willing to take part and follow requirements of the protocol

Patients additionally need to fulfil the following study-specific inclusion criteria:

Cross-sectional study:

• Chronic traumatic SCI (> 12 months after injury) or

• Diagnosed degenerative spondylotic myelopathy (DCM)

Longitudinal study:

• Acute traumatic SCI (< 2 months after injury) or

• Patients with neurogenic lower urinary tract dysfunction (NLUTD) who undergo routine tibial nerve stimulation (TNS) treatment as part of their rehabilitation (but independently of this study) at Balgrist University Hospital

Exclusion Criteria:

• Age < 18 years

• Contraindications for MRI (presence of pacemaker or other type of stimulator in the body, presence of metallic foreign body in or on the body, etc.); we will comply with the imaging center's (SCMI) guidelines and in case of doubt we will exclude the participant from the study

• No informed consent

• History of psychiatric or neurological disease, apart from those induced by SCI (e.g.epilepsy)

• History of skull opening or head trauma

• Known or suspected non-adherence, drug or alcohol abuse

• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc.

• Women who are pregnant (when uncertain, participants will undergo urine testing) or breastfeeding

• Intention to become pregnant during the course of the study

• Body mass index (BMI) > 35

• Individuals especially in need of protection (according to Research with Human Subjects published by the Swiss Academy of Medical Sciences)

Related Conditions & MeSH terms

• Degenerative Cervical Spinal Stenosis
• Neurogenic Bladder Dysfunction
• Spinal Cord Injuries
• Spinal Stenosis
• Urinary Bladder, Neurogenic
• Wounds and Injuries

Locations

Country	Name	City	State
Switzerland	Balgrist University Hospital	Zurich

Sponsors (3)

Lead Sponsor	Collaborator
University of Zurich	Swiss National Science Foundation, Swiss Paraplegic Research

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cross-sectional study: lumbosacral functional fMRI	Activations in the gray matter of the lumbosacral cord, as a response to sensory, motor, and somatosensory stimulations, or no stimulation (resting state). Spatiotemporal components of the BOLD signal as well as the couplings and anti-couplings between these components	Baseline only
Primary	Longitudinal study: lumbosacral functional fMRI	Activations in the gray matter of the lumbosacral cord, as a response to sensory, motor, and somatosensory stimulations, or no stimulation (resting state). Spatiotemporal components of the BOLD signal as well as the couplings and anti-couplings between these component	Change from baseline at 2-month, 6-month, and 12-month
Primary	Cross-sectional study: brain functional MRI	Activations in the cortical and subcortical areas of the brain as a response to sensory, motor, and somatosensory stimulations, or no stimulation (resting state)	Baseline only
Primary	Longitudinal study: brain functional MRI	Activations in the cortical and subcortical areas of the brain as a response to sensory, motor, and somatosensory stimulations, or no stimulation (resting state)	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Cross-sectional study: diffusion MRI in the spinal cord	Directional diffusivities in the spinal cord (units of mm2/s)	Baseline only
Secondary	Cross-sectional study: diffusion MRI in the spinal cord	Fractional anisotropy in the spinal cord (unitless)	Baseline only
Secondary	Longitudinal study: diffusion MRI in the spinal cord	Directional diffusivities in the spinal cord, measured (units of mm2/s)	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Longitudinal study: diffusion MRI in the spinal cord	Fractional anisotropy in the spinal cord (unitless)	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Cross-sectional study: structural MRI in spinal cord	Cross-sectional areas of the spinal cord gray and white matter (units of mm2)	Baseline only
Secondary	Longitudinal study: structural MRI in spinal cord	Cross-sectional areas of the spinal cord gray and white matter (units of mm2)	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Cross-sectional study: magnetic resonance neurography of the lumbosacral plexus	Thickness of nerves and nerve roots (units of mm2)	Baseline only
Secondary	Cross-sectional study: magnetic resonance neurography of the lumbosacral plexus	Nerve entry points into the spinal cord (for determining neurological levels)	Baseline only
Secondary	Longitudinal study: magnetic resonance neurography of the lumbosacral plexus	Thickness of nerves and nerve roots (units of mm2)	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Longitudinal study: magnetic resonance neurography of the lumbosacral plexus	Nerve entry points into the spinal cord (for determining neurological levels)	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Cross-sectional study: diffusion MRI in the brain	Directional diffusivities in the brain (units of mm2/s)	Baseline only
Secondary	Cross-sectional study: diffusion MRI in the brain	Fractional anisotropy in the brain (unitless)	Baseline only
Secondary	Longitudinal study: diffusion MRI in the brain	Directional diffusivities in the brain (units of mm2/s)	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Longitudinal study: diffusion MRI in the brain	Fractional anisotropy in the brain (unitless)	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Cross-sectional study: structural MRI in the brain	Cortical thickness (units of mm)	Baseline only
Secondary	Cross-sectional study: structural MRI in the brain	Volumes of the brain gray and white matter (units of mm3)	Baseline only
Secondary	Longitudinal study: structural MRI in the brain	Cortical thickness (units of mm)	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Longitudinal study: structural MRI in the brain	Volumes of the brain gray and white matter (units of mm3)	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Cross-sectional study: nerve conduction study	Latencies of F waves (units of ms). Period between initial stimulation and F wave elicitation in the tibial and peroneal motor nerves.	Baseline only
Secondary	Cross-sectional study: nerve conduction study	Amplitudes of F waves in the tibial and peroneal motor nerves (units of microV)	Baseline only
Secondary	Cross-sectional study: nerve conduction study	Duration of F waves in the tibial and peroneal motor (units of ms)	Baseline only
Secondary	Longitudinal study: nerve conduction study	Latencies of F waves (units of ms). Period between initial stimulation and F wave elicitation in the tibial and peroneal motor nerves.	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Longitudinal study: nerve conduction study	Amplitudes of F waves in the tibial and peroneal motor nerves (units of microV)	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Longitudinal study: nerve conduction study	Duration of F waves in the tibial and peroneal motor (units of ms)	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Cross-sectional study: motor evoked potentials (MEP)	Latencies (units of ms)	Baseline only
Secondary	Cross-sectional study: motor evoked potentials (MEP)	Amplitudes (units of mV)	Baseline only
Secondary	Longitudinal study: motor evoked potentials (MEP)	Latencies (units of ms)	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Longitudinal study: motor evoked potentials (MEP)	Amplitudes (units of mV)	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Cross-sectional study: American Spinal Injury Association Impairment Scale (AIS) from the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) protocol	AIS quantifies the severity of the spinal cord injury. AIS (ASIA Impairment Scale) grades from A-E, whereas grade A (complete spinal cord injury) is worse than grade E (no impairment)	Baseline only
Secondary	Cross-sectional study: Lower Extremities Motor Scale (LEMS) from the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) protocol	LEMS is based on assessments of ISNCSCI and composed from the sum of muscle function grading of the five key muscles of the lower limbs. It consists of a 6-point scale (0=no; 5=normal activity) for each muscle and body site. The lowest possible score in the total LEMS score for one body site is 0 (symptomatic); the highest possible score is 50 (asymptomatic)	Baseline only
Secondary	Cross-sectional study: Upper Extremities Motor Scale (UEMS) from the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) protocol	UEMS is based on assessments of ISNCSCI and composed from the sum of muscle function grading of the five key muscles of the upper limbs. It consists of a 6-point scale (0=no; 5=normal activity) for each muscle and body site. The lowest possible score in the total UEMS score for one body site is 0 (symptomatic); the highest possible score is 50 (asymptomatic)	Baseline only
Secondary	Cross-sectional study: Light touch (LT) score from the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) protocol	The LT score is based on assessments of ISNCSCI and represents the sum of sensory function of 28 dermatome pairs in terms of light touch sensation. It consists of a 2-point scale (0=absent sensation; 1=altered (impaired or partial sensation, including hyperesthesia); 2 = normal or intact sensation) for each dermatome and body site. The lowest and highest possible LT score for one body site is 0 and 56, respectively	Baseline only
Secondary	Cross-sectional study: Pin prick (PP) score from the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) protocol	The PP score is based on assessments of ISNCSCI and represents the sum of sensory function of 28 dermatome pairs in terms of pin prick discrimination. It consists of a 2-point scale (0=absent discrimination; 1=altered (impaired or partial discrimination); 2 = normal or intact discrimination) for each dermatome and body site. The lowest and highest possible PP score for one body site is 0 and 56, respectively	Baseline only
Secondary	Longitudinal study: American Spinal Injury Association Impairment Scale (AIS) from the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) protocol	AIS quantifies the severity of the spinal cord injury. AIS (ASIA Impairment Scale) grades from A-E, whereas grade A (complete spinal cord injury) is worse than grade E (no impairment).	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Longitudinal study: Lower Extremities Motor Scale (LEMS) from the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) protocol	LEMS is based on assessments of ISNCSCI and composed from the sum of muscle function grading of the five key muscles of the lower limbs. It consists of a 6-point scale (0=no; 5=normal activity) for each muscle and body site. The lowest possible score in the total LEMS score for one body site is 0 (symptomatic); the highest possible score is 50 (asymptomatic)	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Longitudinal study: Upper Extremities Motor Scale (UEMS) from the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) protocol	UEMS is based on assessments of ISNCSCI and composed from the sum of muscle function grading of the five key muscles of the upper limbs. It consists of a 6-point scale (0=no; 5=normal activity) for each muscle and body site. The lowest possible score in the total UEMS score for one body site is 0 (symptomatic); the highest possible score is 50 (asymptomatic)	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Longitudinal study: Light touch (LT) score from the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) protocol	The LT score is based on assessments of ISNCSCI and represents the sum of sensory function of 28 dermatome pairs in terms of light touch sensation. It consists of a 2-point scale (0=absent sensation; 1=altered (impaired or partial sensation, including hyperesthesia); 2 = normal or intact sensation) for each dermatome and body site. The lowest and highest possible LT score for one body site is 0 and 56, respectively	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Longitudinal study: Pin prick (PP) score from the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) protocol	The PP score is based on assessments of ISNCSCI and represents the sum of sensory function of 28 dermatome pairs in terms of pin prick discrimination. It consists of a 2-point scale (0=absent discrimination; 1=altered (impaired or partial discrimination); 2 = normal or intact discrimination) for each dermatome and body site. The lowest and highest possible PP score for one body site is 0 and 56, respectively	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Cross-sectional study: Graded and Redefined Assessment of Strength, Sensation and Prehension (GRASSP)	GRASSP measures sensorimotor and prehension function through three domains (strength, sensation and prehension) which are important in describing arm and hand function. The total GRASSP score ranges from 0 to 116 points, where a higher score indicates a better outcome	Baseline only
Secondary	Longitudinal study: Graded and Redefined Assessment of Strength, Sensation and Prehension (GRASSP)	GRASSP measures sensorimotor and prehension function through three domains (strength, sensation and prehension) which are important in describing arm and hand function. The total GRASSP score ranges from 0 to 116 points, where a higher score indicates a better outcome	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Cross-sectional study: European Multicenter Study about SCI (EMSCI) pain questionnaire	The EMSCI pain questionnaire rates various aspects of pain (e.g., current pain intensity, mean and maximal pain intensity during the last week before the assessment, location and quality of pain, intensity of allodynia and paresthesia). Pain intensity is quantified on an 11-point numeric scale (0=no pain; 10=worst imaginable pain)	Baseline only
Secondary	Longitudinal study: European Multicenter Study about SCI (EMSCI) pain questionnaire	The EMSCI pain questionnaire rates various aspects of pain (e.g., current pain intensity, mean and maximal pain intensity during the last week before the assessment, location and quality of pain, intensity of allodynia and paresthesia). Pain intensity is quantified on an 11-point numeric scale (0=no pain; 10=worst imaginable pain)	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Cross-sectional study: sympathetic skin response including hand, sole and perineum recordings	Latencies (units of ms)	Baseline only
Secondary	Cross-sectional study: sympathetic skin response including hand, sole and perineum recordings	Amplitudes (units of microV)	Baseline only
Secondary	Longitudinal study: sympathetic skin response including hand, sole and perineum recordings	Latencies (units of ms)	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Longitudinal study: sympathetic skin response including hand, sole and perineum recordings	Amplitudes (units of microV)	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Cross-sectional study: Spinal Cord Independence Measure (SCIM III)	The SCIM-III ("Spinal Cord Independence Measure III") score is based on questions concerning independence of persons with a spinal cord injured. It consists of 19 items covering 3 domains, self-care, respiration and sphincter management, and mobility. The self-care subscale ranges from 0 to 20. The respiration and sphincter management subscale ranges from 0 to 40. The mobility subscale ranges from 0 to 40. Total score ranges from 0 (symptomatic) to 100 (asymptomatic). Higher scores reflect higher levels of independence.	Baseline only
Secondary	Longitudinal study: Spinal Cord Independence Measure (SCIM III)	The SCIM-III ("Spinal Cord Independence Measure III") score is based on questions concerning independence of persons with a spinal cord injured. It consists of 19 items covering 3 domains, self-care, respiration and sphincter management, and mobility. The self-care subscale ranges from 0 to 20. The respiration and sphincter management subscale ranges from 0 to 40. The mobility subscale ranges from 0 to 40. Total score ranges from 0 (symptomatic) to 100 (asymptomatic). Higher scores reflect higher levels of independence	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Cross-sectional study: Walking index for Spinal Cord Injury (WISCI)	WISCI is an ordinal 20-point scale (0=unable to stand and/or participate in walking; 20=ambulates with no devices, with brace and no assistance) to assess walking function	Baseline only
Secondary	Longitudinal study: Walking index for Spinal Cord Injury (WISCI)	WISCI is an ordinal 20-point scale (0=unable to stand and/or participate in walking; 20=ambulates with no devices, with brace and no assistance) to assess walking function	Change from baseline at 2-month, 6-month, and 12-month
Secondary	Longitudinal study: International Prostate Symptom Score (IPSS) (only in patients with neurogenic lower urinary tract dysfunction)	The IPSS score is based on questions concerning urinary symptoms and quality of life (QoL). It consists of 8 items covering 7 urinary symptoms related dimensions (subscales) and 1 additional item assessing quality of life. Each item is rated on a 6-point scale (0=not at all; 5=almost always). The lowest possible score in the total IPSS score is 0 (asymptomatic); the highest possible score is 35 (symptomatic). The QoL index is rated on a 7-point scale, with 0 indicating "delighted" and 6 "terrible"	Change between baseline and follow-up (6-12 weeks of tibial nerve stimulation)
Secondary	Longitudinal study: Qualiveen questionnaire (only in patients with neurogenic lower urinary tract dysfunction)	Qualiveen-30 assesses the Specific Impact of Urinary Problems (SIUP) on Quality of Life. It consists of 30 items covering 4 domains, namely inconvenience (9 questions), restrictions (8 questions), fears (8 questions), and impact on daily life (5 questions). Each item is rated on a 5-point ordinal scale (0=asymptomatic; 4=symptomatic). The index of the SIUP on Quality of Life is the mean of the four individual scores. The lowest possible overall score in the Qualiveen-30 is 0 (Urinary problems have no specific impact on QoL); the highest possible score is 30 (Urinary problems have a huge specific impact on QoL)	Change between baseline and follow-up (6-12 weeks of tibial nerve stimulation)
Secondary	Longitudinal study: Urinary Symptom Profile (USP) (only in patients with neurogenic lower urinary tract dysfunction)	The USP score is based on questions concerning urinary symptoms and their severity in males and females. It consists of 13 items covering 3 dimensions (subscales) with 7 overactive bladder (OAB), 3 stress urinary incontinence (SUI), and 3 low stream (LS) related items. Each item is rated on a 4-point scale. The lowest score is 0 (asymptomatic); the highest score is 3 (symptomatic)	Change between baseline and follow-up (6-12 weeks of tibial nerve stimulation)
Secondary	Longitudinal study: Overactive Bladder (ICIQ-OAB) questionnaire (only in patients with neurogenic lower urinary tract dysfunction)	International Consultation on Incontinence Questionnaire Overactive Bladder Quality of Life ICIQ-OAB-QoL is a 26-item questionnaire evaluating quality of life (QoL) in patients with overactive bladder. Scores range from 25-160, with greater values indicating increased impact on quality of life	Change between baseline and follow-up (6-12 weeks of tibial nerve stimulation)