Longitudinal Assessment of Spinal Cord Structural Plasticity Using DTI in SCI Patients

September 9, 2020 updated by: Bing Yao, PhD, Kessler Foundation
This study will apply novel magnetic resonance imaging (MRI) techniques to investigation of spinal cord injury (SCI) to learn how nerve fibers repair and neural cells regain ability to control muscle during the rehabilitation. The information gained will be helpful for physicians to make more accurate diagnosis of SCI, predict injury recovery and movement restoration, and develop more effective treatment plans.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Today, the International Standards for the Neurological Classification of Spinal Cord Injury (ISNSCI) , which includes tests of motor and cutaneous sensory function, and Spinal Cord Independence Measure (SCIM) are the gold standards for neurological classification of spinal cord injury (SCI). These standard measures have very important applications in the rehabilitation of SCI as primary clinical and outcome measures. Despite the importance and usefulness of their applications, these standard measures have their limitations. For example, ISNSCI, intended to be a clinical classification system, is subjective and relatively insensitive to incremental neurophysiological and functional changes during both acute and chronic stages of recovery. Moreover, the ISNSCI cannot evaluate the spinal cord (SC) function bellow the neurological level. For some patients such as children and patients with concomitant brain injuries, reliable evaluation cannot be completed due to their limited cognitive engagement in the evaluation process. Magnetic resonance imaging (MRI) has been proposed as a more objective tool to help clinicians make prognosis. However, recent study showed that conventional clinical MRI does not correlate well with scores measured with ISNSCI.

Diffusion Tensor Imaging (DTI) is an advanced MRI tool capable of probing white matter integrity information through measuring directional diffusion of water molecules, thus providing more microscopic details than conventional MRI. Recent findings suggest that DTI is a promising, non-invasive and objective tool for evaluating and monitoring structural changes within white matter axon pathways after SCI. Our preliminary data showed significant deviation of DTI indices from normative values of healthy subjects in a SCI patient whose conventional T2 scans appeared to be normal (see preliminary data section). A likely explanation for this observed alteration of DTI indices is degeneration and demyelization in descending axonal pathways. Although DTI has been used in animal models to measure the evolution of the injury in the SC and showed great promise in detection of pathological changes in SC, no longitudinal DTI data obtained from human SC are available to indicate sensitivity of DTI technique in detecting SCI progression or recovery. Is DTI capable of detecting structural changes taking place in the SC over the course of rehabilitation in individuals with SCI? Will these measured DTI parameters correlate with ISNSCI-based scores? The fundamental hypothesis of the current study is that rehabilitation can facilitate SC fiber tract repair along with spontaneous adaptations following the injury to help reconnect some of the injured nerve fibers with motoneurons controlling muscles and this will in turn improve the motoneuron activity to promote muscular function, and all these changes can be detected by the proposed longitudinal DTI protocols and standard clinical tools for motor function evaluation. The expected results gained by this longitudinal study would support the application of DTI in monitoring plastic changes in the injured SC and the DTI-derived measures could potentially aid clinicians make more objective diagnosis of the injury and estimate its progression, which are critical in planning targeted therapies. However, it is out of the scope of this proposal to distinguish contributions to structural changes occurring in the SC between spontaneous and treatment factors. Because it is unethical to not treat patients, this limitation cannot be overcome in the current human study. Given the primary focus of the study being longitudinal tracking of SC structural changes using neuroimaging rather than determining relative contributions to these changes by spontaneous recovery and treatment, the limitation should not significantly influence the quality of our study. To test the hypothesis, the investigators propose the following Specific Aims.

Aim 1: Track SC structural changes in patients with incomplete SCI (iSCI) using DTI. Each patient in the proposed study will be scanned covering entire cervical region of the SC using a DTI sequence at baseline, 2 weeks, 1 month, 3 month and 6 month after start of standard rehabilitation intervention. DTI indices (see methods for details) will be quantified and compared across all time points. Previous longitudinal brain DTI human and animal studies suggest that DTI is sensitive to detect brain whiter matter structural changes 24 hours (animal study) and 3 months (unpublished human DTI results by PI's group) after brain injury, and 6 month after initial scan in patients with Amyotrophic lateral sclerosis(ALS) (DTI data were only available 6 months after initial scan in this study). The investigators hypothesize that the proposed DTI protocol will be able to capture structural changes in SCI during its recovery course.

Aim 2: Correlate the SC plasticity manifested by changes in DTI indices with clinical assessments of injury and sensorimotor function. Quantitative DTI indices will be correlated to clinical diagnoses of SCI and clinical evaluations of upper and lower limb sensorimotor function of the patients. It is hypothesized that the DTI index of SCI will significantly be correlated with clinical diagnosis and scores of upper and lower sensorimotor function. The DTI parameter holds great promise to be a biomarker of SCI and is expected to have prognostic value in predicting functional outcome of a rehabilitation program.

Study Type

Observational

Enrollment (Actual)

19

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Jersey
      • West Orange, New Jersey, United States, 07052
        • Kessler Foundation

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Twelve (12) individuals with iSCI (within 3 weeks post injury) will be recruited from Kessler Institute for Rehabilitation (KIR). In addition, we will recruit twelve healthy age- and gender-matched controls. All participants will give informed consent. For the SCI group the following clinical evaluations will occur at baseline, 2 weeks, 1 month, 3 months and 6 months by the study physician or clinician.

Description

Inclusion Criteria:

  • SCI due to single event traumatic injury; C4-T12 neurological level of injury, AIS grade B,C or D;
  • currently medically stable;
  • no history of seizure;
  • spasticity at a score of 2 or lower assessed using Modified Ashworth Assessment of the upper and lower extremities;
  • able to give informed consent;
  • to stay still in the MR scanner for ~30 min.

Exclusion Criteria:

  • MRI contraindications;
  • younger than 18 and older than 75 years (this age range will limit contributions from nervous system development and aging to results of the study);
  • history of epilepsy and other neurological diseases and trauma;
  • drug and alcohol abuse;
  • multi injury levels;
  • severe craniocerebral injury and
  • presence of non-MRI-safe post-operative hardware in the spine or brain.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patient
SCI patients enrolled at Kessler Institute Rehabiliation
Other: Standard Rehabilitative Treatment
The patients will participate in standard but comprehensive SCI specific rehabilitation therapy provided by the SCI program at KIR. The therapy consists of 3 hours per day, 5 days a week. Motor function therapy includes standardized procedures for range of motion, passive and active muscle activities, and therapies to improve mobility. The treatment program for the enrolled patients will be standardized by Dr. Kirshblum, Director of the SCI program at KIR and a Co-Investigator of the study. Patients usually receive 4 weeks of rehabilitation treatment; however, if any of them are discharged earlier from KIR, their out-patient treatment activities will be monitored and the patients will be tested based on the planned schedule.
Control
age and gender matched with patient enrolled

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI)
Time Frame: changes within 6 months after participant enrolls.
Neurological examination will be performed using the ISNCSCI. Sensory scores and lower and upper extremity motor scores (LEMS and UEMS) are derived at the time of this exam. The ISNCSCI and all examinations described below will be performed following the same schedule as the imaging (DTI, T2, T2*) evaluation (baseline, 2 weeks, 1 month, 3 months, and 6 months after commencement of rehabilitation therapy). The LEMS measures strength in five muscle groups bilaterally (hip flexors, knee flexors, extensors, and ankle dorsiflexors) and the UEMS also assess strength bilaterally in 5 muscle groups (elbow flexors, elbow extensors, wrist extensors, finger flexors, finger abductors) with the modified British Medical Research Council scale and is performed during the ISNCSCI examination.
changes within 6 months after participant enrolls.
Modified Ashworth Scale (MAS)
Time Frame: changes within 6 months after participant enrolls.
Spasticity assessments will be performed at each visit using the MAS. It tests the resistance to passive movement about a joint with vary degrees of velocity. The scores range from 0 to 4, with 6 choices (0, 1, 1+, 2, 3, and 4). A score of 0 indicates no resistance, and 4 indicates rigidity. The MAS scores will be averaged across 5 muscle groups bilaterally for lower extremities and 5 muscle groups for upper extremities. An experienced therapist will perform all the evaluations for all the visits and all subjects.
changes within 6 months after participant enrolls.
Spinal Cord Independence measure III (SCIM III)
Time Frame: changes within 6 months after participant enrolls.
The SCIM is a measure of functional ability developed specifically for individuals with SCI to evaluate their performance of activities of daily living and to make functional assessments of this population sensitive to change. SCIM scores a task higher in patients who accomplish it with less assistannce, aids, or medical compromise than other patients. The SCIM III to be adopted by the current study is composed of 19 items in 3 subscales: (a) self-care; (b) respiration and sphincter management; and (c) mobility. The total score ranges from 0 to 100. Mobility is subdivided into "room and toilet" and "indoors and outdoors". The items are weighted in terms of their assumed clinical relevance. The SCIM III is a valid and reliable measure and is recommended as a primary outcome measure to assess functional recovery in individuals with SCI.
changes within 6 months after participant enrolls.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diffusion Tensor Image
Time Frame: before [baseline] and 2 weeks, 1 month, 3 months and 6 months after commencement of rehabilitative treatment)
Being an advanced MRI tool, DTI provides excellent structural information on microscopic level such as remyelination which plays an important role in rehabilitation of SCI.
before [baseline] and 2 weeks, 1 month, 3 months and 6 months after commencement of rehabilitative treatment)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kessler Foundation

Investigators

  • Principal Investigator: Bing Yao, Ph.D., Kessler Fondation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2016

Primary Completion (Actual)

March 31, 2020

Study Completion (Actual)

March 31, 2020

Study Registration Dates

First Submitted

February 14, 2017

First Submitted That Met QC Criteria

February 27, 2017

First Posted (Actual)

March 3, 2017

Study Record Updates

Last Update Posted (Actual)

September 11, 2020

Last Update Submitted That Met QC Criteria

September 9, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Kessler

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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