Spasticity and Functional Recovery After SCI

Spasticity and Functional Recovery in Humans With Acute to Subacute Spinal Cord Injury.

Spasticity is one of the most common symptoms manifested in humans with spinal cord injury (SCI). However, the neural mechanisms underlying the development of spasticity over time after an acute SCI are not yet understood. Using electrophysiological and imaging techniques along with traditional measurements of neurological recovery in the acute rehabilitation setting including physical exam and functional assessments; the investigators aim to examine the relationship between development of spasticity, residual descending motor pathways and functional and neurological recovery in humans with SCI from acute to subacute phase

Study Overview

• Status: Enrolling by invitation
• Conditions: Spinal Cord Injuries; Acute Spinal Cord Injury
• Intervention / Treatment: Other: Measures of spasticity, connectivity and analysis of single nucleotide polymorphisms and biomarkers of inflammation; Other: Analysis of biomarkers

Detailed Description

The purpose of this study is to measure changes to motor-evoked potentials (MEPs) and to evaluate if the development of spasticity is related to residual descending motor pathways and to a better neurological recovery and functional improvement in individuals with SCI from the acute to the subacute phase. The investigators will also test for the presence of biological markers in the blood that may correlate with levels of spasticity or neurological recovery and functional improvement, including the presence or absence of neuroplastic genetic polymorphisms (e.g. BDNF Val66Met polymorphism), as well as circulating levels of neuroplastic (e.g. BDNF) or inflammatory factors (e.g. interleukins, TNF) that may affect neuronal growth and functional restoration.

• Study Type: Observational
• Enrollment (Estimated): 240

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Shirley Ryan AbilityLab

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Prospective participants who meet the study inclusion criteria will be identified by bi-weekly chart review ofall new admissions to the acute inpatient spinal cord injury unit at the Shirley Ryan AbilityLab (SRAlab).Eligible patients will be invited to participate by the clinical staff during their first week of admission.

Prospective participants that meet the inclusion criteria for the Control group will be recruited using various sources including the Shirley Ryan AbilityLab non-patient research database, participants who have taken part in our earlier studies, word of mouth, people who work at or visit our center and are interested in research participation.

Description

Individuals with SCI:

Inclusion criteria:

• Male and females 18 years of age or greater
• Basic proficiency in English language communication
• Are admitted to the Shirley Ryan AbilityLab as a spinal cord injury patient
• International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) level above L2
• American Spinal Cord Injury Association Impairment Scale (AIS) grades A, B, C, or D
• Patients with SCI within the first week of inpatient admission to the Shirley Ryan AbilityLab after sustaining a SC

Exclusion criteria:

• Under 18 years of age
• Severe cognitive impairment that precludes the ability to participate in a comprehensive physical exam or give verbal consent
• ISNCSCI level below L2
• People who have sustained SCI >30 days
• 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
• Vascular, traumatic, tumoral, infectious, or metabolic lesion of the brain, even without history of seizure, and without anticonvulsant medication
• History of seizures or epilepsy
• Ongoing cord compression or a syrinx in the spinal cord or people who suffer from a spinal cord disease such as spinal stenosis, spina bifida, MS, or herniated disk 13. Metal plate in skull
• Individuals with scalp shrapnel, cochlear implants, or aneurysm clips
• Skull fractures, skull deficits or concussion within the last 6 months
• Presence of orthoses and presence of spinal precautions or healing incisions that make the area inaccessible to the testing procedures. This criterion will be applied as needed for the specific study procedures that may need to access the areas under restriction.
• Formal diagnosis of Post-Traumatic Stress Disorder (PTSD)

Individuals in the control group:

Inclusion criteria:

1. Male and females 18 years of age or greater
2. Basic proficiency in English language communication

Exclusion criteria:

1. Under 18 years of age
2. Uncontrolled medical problems including pulmonary, cardiovascular, or orthopedic disease
3. History of neurological impairment or conditions affecting the Central Nervous System
4. Premorbid, ongoing major depression or psychosis, altered cognitive status
5. Pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Inpatients; Prospective participants who meet the study inclusion criteria will be identified by bi-weekly chart review of all new admissions to the acute inpatient spinal cord injury unit at the Shirley Ryan AbilityLab (SRAlab). Eligible patients will be invited to participate by the clinical staff during their first week of admission.	Other: Measures of spasticity, connectivity and analysis of single nucleotide polymorphisms and biomarkers of inflammation; We will test for presence of biological markers in blood that may correlate with levels of spasticity or neurological recovery and functional improvement, including the presence or absence of neuroplastic genetic polymorphisms (e.g. BDNF Val66Met polymorphism), as well as circulating levels of neuroplastic(e.g. BDNF) or inflammatory factors (e.g. interleukins, TNF) that may affect neuronal growth and functional restoration.; Other: Analysis of biomarkers; We will test for the presence of biological markers in the blood to compare the distribution of polymorphisms and biomarkers with the spinal cord injury patient population.
Control group; We will enroll non-injured healthy individuals to compare the level of biomarkers	Other: Analysis of biomarkers; We will test for the presence of biological markers in the blood to compare the distribution of polymorphisms and biomarkers with the spinal cord injury patient population.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Ashworth scale (MAS)	This clinical scale will be used by measuring resistance encountered during manual passive muscle stretching using a six-point ordinal scale (0=no increase in tone, 1/+1=slight increase in tone with a catch and release or minimal resistance at the end or less than half of the range of movement, respectively, 2=more marked increased tone through most of the range of movement but affected parts easily moved, 3=considerable increase in tone and passive movement difficultly, and 4=affected parts rigid)	From the time of admission to the hospital and enrolled in the study till the time of discharge (up to 12 weeks)
Motor evoked potential (MEP)	Transcranial magnetic stimulation will be delivered and the coil will be positioned over the vertex and moved around this point to determine the optimal position for eliciting a motor evoked potentials (MEPs) in legs muscles.	From the time of admission to the hospital and enrolled in the study till the time of discharge (up to 12 weeks)
First swing test (FST)	We will use the pendulum test to measure muscle tone at the knee by using gravity to provoke muscle stretch reflexes during passive swinging of the lower limb.	From the time of admission to the hospital and enrolled in the study till the time of the discharge (up to 12 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI)	At the time of the admission, after obtaining consent, and at the time of discharge, the chart will be reviewed to obtain the ISNCSCI score	From the time of admission to the hospital and enrolled in the study till the time of discharge (up to 12 weeks)
Circulating biomarkers of inflammation and neuroplasticity	In this study, we will focus on tracking expression of key inflammatory cytokines that have been shown to play a pivotal role in activating the major nuclear factor kappa-B (NF-κB) inflammatory pathway. Specifically, we will characterize serum levels of pro-inflammatory cytokines interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and anti-inflammatory marker interleukin-10 (IL-10). We will also measure levels of circulating neuroplasticity marker Brain-derived neurotrophic factor (BDNF)	From the time of admission to the hospital and enrolled in the study till the time of discharge (up to 12 weeks)

Collaborators and Investigators

• Sponsor: Shirley Ryan AbilityLab
• Investigators: Principal Investigator: Monica A Perez, PT, PhD, Shirley Ryan AbilityLab

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: April 7, 2022
• First Submitted That Met QC Criteria: September 1, 2023
• First Posted (Actual): September 11, 2023

Study Record Updates

• Last Update Posted (Actual): September 11, 2023
• Last Update Submitted That Met QC Criteria: September 1, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Recovery; Bio-markers; Spasticity
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Trauma, Nervous System; Spinal Cord Diseases; Muscle Hypertonia; Wounds and Injuries; Spinal Cord Injuries; Muscle Spasticity
• Other Study ID Numbers: STU00210582

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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