Clinical trial NCT04393922: Spasticity After Spinal Cord Injury
Official title: Spasticity After Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Spinal Cord Injuries
Keywords: Spinal cord injury, Spasticity, TMS
Lead sponsor: Shirley Ryan AbilityLab
Sponsor class: OTHER
First posted: 2020-05-19
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Very often, people who have a SCI have difficulty doing things with their arms or hands as a result of muscle stiffness , or spasticity. Spastacity can cause problems performing even the simplest of everyday tasks. This research will help us understand how the body recovers and changes neurologically after SCI.

Detailed description: After spinal cord injury (SCI), damage to descending motor pathways has been associated with the development of spasticity (Frigon and Rossignol, 2006; Trompetto et al., 2014). Self-reported questionnaires and clinical exams indicate that individuals with incomplete SCI, who showed residual descending connectivity, have a high prevalence of spasticity compared to individuals with complete SCI (Little et al., 1989; Holtz et al., 2017). In agreement, our recent electrophysiological and spinal cord imaging data in humans with a diagnosis of a clinically motor complete SCI showed the presence of descending motor pathway connectivity in individuals with spasticity compared to those without spasticity (Sangari et al., 2019). However, which descending motor pathways influence spasticity following SCI, and to what extent, remains poorly understood. This proposal has two main goals: 1) to examine the contribution of cortico- and reticulo-spinal pathways to spasticity in upper and lower limb muscles, and 2) to develop strategies to promote functional recovery of upper and lower limb spastic muscles in humans with chronic incomplete SCI. The aims below will test two main hypotheses.

In Aim 1, we will use transcranial magnetic stimulation and startle acoustic stimuli to examine the contribution of the cortico- and reticulo-spinal pathway to upper and/or lower limb muscles electromyographic activity. Spinal cord atrophy and morphological characterization of cortico- and reticulo-spinal pathways will be assessed with high-resolution magnetic resonance imaging. Physiological and neuroimaging outcomes will be associated with clinical assessment of spasticity.

In Aim 2, we propose to enhance cortico- and reticulo-spinal contribution to upper and/or lower limb function in spastic muscles by using a novel intervention combining startle acoustic stimuli with motor training.

This research will provide new knowledge about the contribution of descending motor pathways to the control of spasticity in upper and lower limb muscles following incomplete cervical SCI (Aim1) and might lead to the development of a novel rehabilitation intervention to improve upper and lower limb motor function recovery by enhancing residual descending control over spinal networks (Aim 2).

Eligibility criteria: Inclusion criteria for individuals with SCI

* Chronic SCI (≥1 year of injury)
* Incomplete spinal cord injury at T12 or above
* Males and Females
* Ages 18-75 years

Inclusion criteria for non-spastic individuals with SCI

-MAS scores of 0 and 1

Inclusion criteria for spastic individuals with SCI

* MAS scores of 2, 3 and 4
* The ability to perform a voluntary flexion and extension of the elbow and/or knee or ankle
* The ability to reach and grasp an object

Inclusion criteria for health controls

* Males and females
* Ages 18-75 years
* Right-handed
* Able to perform elbow and/or knee or ankle flexion and extension

Exclusion Criteria for individuals with SCI and healthy controls:

* Uncontrolled medical problems including pulmonary, cardiovascular, or orthopedic disease
* Any debilitating disease prior to the SCI that caused exercise intolerance
* Premorbid, ongoing major depression or psychosis, altered cognitive status
* History of head injury or stroke
* Pacemaker
* Metal plate in skull
* History of seizures
* Receiving drugs acting primarily on the central nervous system, which lower the seizure threshold such as antipsychotic drugs (chlorpromazine, clozapine) or tricyclic antidepressants
* Pregnant females
* Ongoing cord compression or a syrinx in the spinal cord or who suffer from a spinal cord disease such as spinal stenosis, spina bifida, or herniated cervical disk

Primary outcomes:
measure: MEP recruitment curves
timeFrame: 3-4 hours
measure: Ipsilateral MEPs (iMEPs)
timeFrame: 3-4 hours
measure: StartReact
timeFrame: 3-4 hours
measure: Participant reported spasticity
timeFrame: 3-4 hours
measure: Modified Ashworth Scale (MAS)
timeFrame: 3-4 hours
measure: Portable Spasticity Assessment Device (PSAD)'
timeFrame: 3-4 hours
measure: Pendulum Test
timeFrame: 3-4 hours
measure: 10-meter walk test
timeFrame: 3-4 hours
measure: Graded and Redefined Assessment of Strength, Sensibility and Prehension (GRASSP).
timeFrame: 3-4 hours
measure: Toronto Rehabilitation Institute-Hand Function Test (TRI-HFT)
timeFrame: 3-4 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Shirley Ryan AbilityLab
state: Illinois
Study officials:
References: