Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Investigation of Brain Functional MRI as an Early Biomarker of Recovery in Individuals With Spinal Cord Injury

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03854214
Recruitment Status : Not yet recruiting
First Posted : February 26, 2019
Last Update Posted : February 27, 2019
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Ann Choe, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Brief Summary:
Early detection of response to therapeutic intervention is vital, as it will enable early termination of intervention in non-responding patients, prevent unnecessary financial burden, and allow for early changes to the intervention program. Previous functional MRI (fMRI) studies have shown that changes in brain functional network in spinal cord injury (SCI) patients can occur after as little as one week of intervention. Resting state fMRI (rsfMRI) is a type of fMRI that does not require performance of explicit motor tasks, which makes the method especially suitable for SCI patient population. In this project, the investigators propose that rsfMRI outcome measures can be used to detect early brain functional network changes that occur during intervention, and that the changes will be predictive of recovery in chronic SCI patients.

Condition or disease Intervention/treatment Phase
Spinal Cord Injuries Device: Functional Electric Stimulation cycling Device: Passive cycling Early Phase 1

Detailed Description:
Early detection of response to spinal cord injury (SCI) therapeutic intervention programs is vital, as it will enable early termination of intervention in non-responding patients, prevent unnecessary financial burden, and allow for early changes of the programs. In this project, the investigators propose that resting state functional MRI (rsfMRI) can be used to detect early brain functional network changes that occur during intervention, and that the changes will be predictive of recovery in chronic SCI patients. The long-term goal of this study is to establish rsfMRI as a new imaging biomarker that is predictive of progress towards recovery in response to therapy. International Standard of Neurological Classification for Spinal Cord Injury (ISNCSCI) scoring system is the most widely used clinical classification system of SCI that describes neurological injury level and degree of functional preservation. It is also used to monitor the progress and response to interventions such as functional electrical stimulation (FES) therapy. However, monitoring responses using ISNSCI is challenging, because its ability to describe the degree of functional loss is limited. Therefore, there is a need in the field of SCI for a biomarker that is more sensitive to changes in function. The investigators will recruit 2 groups of 24 chronic SCI patients. In one group, the investigators will characterize the baseline time profile of rsfMRI outcome measures acquired during a 4-weeks passive cycling program, where movement is driven only by the cycle's motor (no electric stimulation). RsfMRI data of the patients acquired at weeks 0, 2, and 4 will be used perform functional parcellation of the sensorimotor cortex using independent component analysis (ICA) and spectral clustering analysis (SCA) approaches. BNC will be calculated between pairs of sensory and motor brain parcels. Sensory and motor ISNCSCI scores will also be measured at weeks 0, 2, and 4. The investigators will then test the hypothesis that the investigators will observe stable baseline measures of sensory and motor cortex BNC and ISNCSCI scores of the patients during the 4-week passive cycling program, with minimal to no change in values. In the second group, the investigators will characterize the time profile of the cortical reorganization in chronic SCI patients that occurs during the four-week FES cycling. Specifically, the investigators predict that the investigators will observe early functional network changes in the sensorimotor cortex of SCI patients (measured using BNC) at week 2 of the four-week FES cycling program, which will be predictive of changes in ISNSCI scores (neurological outcomes) at week 4. Finally, the longitudinal intra-subject reproducibility of the two parcellation methods will be investigated. If successful, the study will: 1) provide a new and effective clinical tool to study plastic cortical changes that occur after SCI, 2) provide a new non-invasive imaging biomarker that is predictive of progress towards recovery in response to therapy, and 3) extend our knowledge about the functional reorganization that takes place during and after therapeutic intervention.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

The study will be performed as a randomized, parallel group trial to determine if the amount of changes in brain functional connectivity outcome measures (i.e., between network connectivity) is significantly different between the group of patients that perform FES cycling and another group of patients that perform passive (sham) cycling.

Official screening will be performed after participants consent by signing the study's consent form. Participants will be randomized into 2 groups: FES cycling (Group 1; n=24) and passive cycling (Group 2; n=24). The participants will undergo either an FES cycling or a passive cycling sessions for 4 weeks, 3 times a week. MRI will be performed on all participants at the beginning (prior to cycling sessions) and at the end of the 2nd and 4th weeks of the intervention program. ISNCSCI evaluations will be performed to coincide with the dates of MRI acquisitions, to determine the neurological level and the degree of sensory and motor impairments.

Masking: Double (Participant, Care Provider)
Masking Description: This study is a double-blinded randomized trial. Study physicians and research staff who perform study measurements on participants will be blinded from the intervention the study participants receive. Study participants will not be informed of the intervention he/she will receive. However, because of the nature of the interventions, study participant cannot be completely blinded to the treatment they will receive, as some participants may have residual motor and sensory functions and 'feel' which intervention they are receiving.
Primary Purpose: Basic Science
Official Title: Cortical Functional Connectivity as an Early Biomarker of Recovery in Spinal Cord Injury
Estimated Study Start Date : April 2019
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Functional Electric Stimulation cycling
The Functional Electrical Stimulation (FES) cycling group will use RT300 ergometer (Restorative Therapies, Inc) with stimulation on.
Device: Functional Electric Stimulation cycling
The Functional Electrical Stimulation (FES) cycling group will use RT300 ergometer (Restorative Therapies, Inc). Bilateral glutei, quadriceps and hamstrings will be stimulated. The stimulation parameters will be set as follows: waveform biphasic, charged balanced; phase duration of 250 microseconds; pulse rate 33-45 pps. The stimulus intensity will be adjusted for individual patients and muscle group so that a tolerable stimulation is provided that will generate a cycling action. Target cycling speed is 50 RPM. Resistance will be automatically adjusted by the FES bike according to the subject's performance. When fatigue occurs, participants will continue cycling with electrical stimulation and motor support. FES therapy will be administered for one hour per session 3 times a week.
Other Name: RT300 ergometer

Sham Comparator: Passive Cycling
The passive cycling group will use the same RT300 ergometer with stimulation off.
Device: Passive cycling
The passive cycling group will use the same RT300 ergometer however during this period stimulation will not be turned on. Instead, continuous motor support will be activated resulting in passive cycling. Target cycling speed is 50 RPM. Participants assigned to passive cycling will be required to have one hour of passive therapy 3 times a week for the entire duration of treatment assignment.
Other Name: RT300 ergometer




Primary Outcome Measures :
  1. International Standard of Neurological Classification for Spinal Cord Injury (ISNCSCI) score [ Time Frame: Change from baseline ISNCSCI scores at 2 weeks and 4 weeks after the start of intervention. ]
    Developed by the American Spinal Injury Association (ASIA) as a universal classification tool for spinal cord injury (SCI), the classification tool involves a sensory and motor examination to determine the neurological level of the injury and whether the injury is complete or incomplete. The tool also provides sensory and motor scores of upper and lower, as well as right and left sides of the body. The value of the total motor score ranges between 0-100, where 0 represents no residual motor function, and 100 represents normal motor function. The sensory scores consists of two sub-scores - specifically, light touch and pin-prick scores. The values of each sub-score ranges between 0-112, where 0 represents no residual sensory function, and 112 represents normal sensory function. The ISNCSCI defines neurological level as the most caudal level at which sensory and motor function are intact. The completeness of the injury is graded according to the ASIA Impairment Scale (AIS).

  2. Resting state fMRI functional connectivity [ Time Frame: Change from baseline functional connectivity at 2 weeks and 4 weeks after the start of intervention. ]
    RsfMRI functional connectivity is defined as the temporal dependency of neuronal activation patterns (represented by the blood oxygenation level dependent (BOLD) signal time courses as measured using rsfMRI) of anatomically separated brain regions. There are number of methodologies one can use to characterize the degree and type of rsfMRI functional connectivity. One example is between-network-connectivity (BNC), which is defined as the degree of correlation between two time courses obtained from a pair of brain regions. Summary statistics of BNC (e.g., mean, variance), as well as the dynamic properties of BNC (e.g., dynamic functional connectivity) can be used to further summarize the characteristics of the functional connectivity in SCI population

  3. Resting state fMRI brain parcels [ Time Frame: Change from baseline fMRI brain parcels at 2 weeks and 4 weeks after the start of intervention. ]
    RsfMRI functional connectivity can also be used to identify functionally homogeneous brain regions, or parcels of the brain. The parcels' center of mass, average and variance of the BOLD signal time courses within the parcels can be used to characterize brain functional organization.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult (18-65 years) men and women of all ethnic groups
  • SCI, traumatic
  • Thoracic neurological level, without the involvement of lower motor neurons.
  • ASIA classification A-D
  • Chronic injury: > 6 months from the injury
  • Satisfactory general health
  • No FES ergometer (i.e. RT300 or equivalent) use within 4 weeks.
  • Ability to comply with procedures and follow-up

Exclusion Criteria:

  • Contra-indication to MR study (e.g., cardiac pacemaker, claustrophobia, aneurysm clip, etc.)
  • History or clinical evidence of moderate or severe brain injury
  • Major spine deformity (e.g. scoliosis, kyphosis, subluxation)
  • Movement disorder or severe spasticity preventing ability to lay still for extended periods required for imaging.
  • Women who are pregnant
  • Concurrent lower motor neuron disease such as peripheral neuropathy that would exclude lower extremity electrical excitability
  • Unstable long bone fractures of the lower extremities.
  • Subjects with history of inability to tolerate electrical stimulation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03854214


Contacts
Layout table for location contacts
Contact: Ann S Choe, Ph.D. 443-923-9500 annschoe@gmail.com

Sponsors and Collaborators
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Layout table for investigator information
Principal Investigator: Ann S Choe, Ph.D. Johns Hopkins University

Publications:
Layout table for additonal information
Responsible Party: Ann Choe, Assistant Professor, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
ClinicalTrials.gov Identifier: NCT03854214     History of Changes
Other Study ID Numbers: 00182576
R21NS104644-01A1 ( U.S. NIH Grant/Contract )
First Posted: February 26, 2019    Key Record Dates
Last Update Posted: February 27, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All research material will be kept confidential and any means of subject identification (name and history number) will be removed from all material for analysis or presentation. No identifying information will be made publicly available. In some cases, the study protocol, statistical analysis plan, individual scans, and all IPD that underlie results in a publication will be included in published papers or meeting papers or posters, but the identity of the subject in question will not be revealed.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Starting immediately after publication
Access Criteria: All IPD that underlie results in a publication will be available to the extent the related publication(s) allows it. However, under no circumstances any IPD that contains subject identification information will be shared.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Ann Choe, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.:
Spinal Cord Injuries
MRI, Functional
Rehabilitation
Neuronal Plasticity

Additional relevant MeSH terms:
Layout table for MeSH terms
Wounds and Injuries
Spinal Cord Injuries
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System