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

NCT ID: NCT03854214

Last Updated: 2025-03-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-01
• Study Completion Date: 2023-12-31

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.

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 ISNCSCI 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 ISNCSCI 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.

Conditions

Spinal Cord Injuries

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Functional Electric Stimulation cycling

The Functional Electrical Stimulation (FES) cycling group will use RT300 ergometer (Restorative Therapies, Inc) with stimulation on.

Group Type: ACTIVE_COMPARATOR

Functional Electric Stimulation cycling

Intervention Type: DEVICE

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 revolutions per minute (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.

Passive Cycling

The passive cycling group will use the same RT300 ergometer with stimulation off.

Group Type: SHAM_COMPARATOR

Passive cycling

Intervention Type: DEVICE

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.

Interventions

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 revolutions per minute (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.

Intervention Type: 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.

Intervention Type: DEVICE

Other Intervention Names

RT300 ergometer; RT300 ergometer

Eligibility 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.
• American Spinal Injury Association (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 Magnetic Resonance (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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

OTHER

Sponsor Role: lead

Responsible Party

Ann Choe

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ann S Choe, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Kennedy Krieger Institute, International Center for Spinal Cord Injury

Baltimore, Maryland, United States

Countries

United States

References

Choe AS. Advances in Spinal Functional Magnetic Resonance Imaging in the Healthy and Injured Spinal Cords. Curr Phys Med Rehabil Rep. 2017 Sep;5(3):143-150. doi: 10.1007/s40141-017-0161-x. Epub 2017 Jul 31.

Reference Type: BACKGROUND

PMID: 29255645 (View on PubMed)

Choe AS, Nebel MB, Barber AD, Cohen JR, Xu Y, Pekar JJ, Caffo B, Lindquist MA. Comparing test-retest reliability of dynamic functional connectivity methods. Neuroimage. 2017 Sep;158:155-175. doi: 10.1016/j.neuroimage.2017.07.005. Epub 2017 Jul 5.

Reference Type: BACKGROUND

PMID: 28687517 (View on PubMed)

Choe AS, Jones CK, Joel SE, Muschelli J, Belegu V, Caffo BS, Lindquist MA, van Zijl PC, Pekar JJ. Reproducibility and Temporal Structure in Weekly Resting-State fMRI over a Period of 3.5 Years. PLoS One. 2015 Oct 30;10(10):e0140134. doi: 10.1371/journal.pone.0140134. eCollection 2015.

Reference Type: BACKGROUND

PMID: 26517540 (View on PubMed)

Choe AS, Belegu V, Yoshida S, Joel S, Sadowsky CL, Smith SA, van Zijl PC, Pekar JJ, McDonald JW. Extensive neurological recovery from a complete spinal cord injury: a case report and hypothesis on the role of cortical plasticity. Front Hum Neurosci. 2013 Jun 25;7:290. doi: 10.3389/fnhum.2013.00290. eCollection 2013.

Reference Type: BACKGROUND

PMID: 23805087 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R21NS104644

Identifier Type: NIH

Identifier Source: secondary_id

View Link

00182576

Identifier Type: -

Identifier Source: org_study_id