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

NCT03854214 | Completed Results FDA Device

• 2 other identifiers: 00182576R21NS104644
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Spinal Cord Injuries

Keywords

Spinal Cord Injuries; MRI, Functional; Rehabilitation; Neuronal Plasticity

Outcome Measures

Primary Outcomes (9)

• International Standard of Neurological Classification for Spinal Cord Injury (ISNCSCI) Score

  Developed by the American Spinal Injury Association (ASIA), the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) provides an overall assessment of motor and sensory function following spinal cord injury. For this study, a single composite ISNCSCI score is reported, which ranges from 0 (indicating the worst overall function) to 324 (indicating normal overall function). The data table presents this composite score as the sole outcome measure for each Arm/Group.

  Baseline

• International Standard of Neurological Classification for Spinal Cord Injury (ISNCSCI) Score

  Developed by the American Spinal Injury Association (ASIA), the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) provides an overall assessment of motor and sensory function following spinal cord injury. For this study, a single composite ISNCSCI score is reported, which ranges from 0 (indicating the worst overall function) to 324 (indicating normal overall function). The data table presents this composite score as the sole outcome measure for each Arm/Group.

  2 weeks

• International Standard of Neurological Classification for Spinal Cord Injury (ISNCSCI) Score

  Developed by the American Spinal Injury Association (ASIA), the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) provides an overall assessment of motor and sensory function following spinal cord injury. For this study, a single composite ISNCSCI score is reported, which ranges from 0 (indicating the worst overall function) to 324 (indicating normal overall function). The data table presents this composite score as the sole outcome measure for each Arm/Group.

  4 weeks

• Resting State fMRI Functional Connectivity

  Resting state functional magnetic resonance imaging (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. Note that the BNC values reported in the Outcome Measure data table represent "Pearson's Correlation Coefficient" and not z-transformed Pearson's Correlation Coefficients.

  Baseline

• Resting State fMRI Functional Connectivity

  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. Note that the BNC values reported in the Outcome Measure data table represent "Pearson's Correlation Coefficient" and not z-transformed Pearson's Correlation Coefficients.

  2 weeks

• Resting State fMRI Functional Connectivity

  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. Note that the BNC values reported in the Outcome Measure data table represent "Pearson's Correlation Coefficient" and not z-transformed Pearson's Correlation Coefficients.

  4 weeks

• Resting-State fMRI Brain Parcels Outcome Measure: Sensorimotor Network (SMN) Recruitment Coefficient

  Resting-state functional connectivity can also identify functionally homogeneous brain regions, or "parcels." By examining each parcel's properties, such as the center of mass and recruitment coefficient value, we can gain insights into the brain's functional reorganization. Given its importance in the SCI population, we focused on the sensorimotor network (SMN) parcel. RsfMRI data were collected and preprocessed. The brain data was then parcellated into 200 parcels. Next, a multi-layer community detection algorithm was applied to identify cohesive subnetworks over time, and the SMN Recruitment Coefficient was calculated - which is a dimensionless metric that quantifies how strongly the SMN parcels cohere, or preferentially connect, with one another compared to parcels in other networks. Higher values suggest a more internally cohesive SMN, indicating stronger functional segregation and potentially more intact sensorimotor function.

  Baseline

• Resting-State fMRI Brain Parcels Outcome Measure: Sensorimotor Network (SMN) Recruitment Coefficient

  Resting-state functional connectivity can also identify functionally homogeneous brain regions, or "parcels." By examining each parcel's properties, such as the center of mass and recruitment coefficient value, we can gain insights into the brain's functional reorganization. Given its importance in the SCI population, we focused on the sensorimotor network (SMN) parcel. RsfMRI data were collected and preprocessed. The brain data was then parcellated into 200 parcels. Next, a multi-layer community detection algorithm was applied to identify cohesive subnetworks over time, and the SMN Recruitment Coefficient was calculated - which is a dimensionless metric that quantifies how strongly the SMN parcels cohere, or preferentially connect, with one another compared to parcels in other networks. Higher values suggest a more internally cohesive SMN, indicating stronger functional segregation and potentially more intact sensorimotor function.

  2 weeks

• Resting-State fMRI Brain Parcels Outcome Measure: Sensorimotor Network (SMN) Recruitment Coefficient

  Resting-state functional connectivity can also identify functionally homogeneous brain regions, or "parcels." By examining each parcel's properties, such as the center of mass and recruitment coefficient value, we can gain insights into the brain's functional reorganization. Given its importance in the SCI population, we focused on the sensorimotor network (SMN) parcel. RsfMRI data were collected and preprocessed. The brain data was then parcellated into 200 parcels. Next, a multi-layer community detection algorithm was applied to identify cohesive subnetworks over time, and the SMN Recruitment Coefficient was calculated - which is a dimensionless metric that quantifies how strongly the SMN parcels cohere, or preferentially connect, with one another compared to parcels in other networks. Higher values suggest a more internally cohesive SMN, indicating stronger functional segregation and potentially more intact sensorimotor function.

  4 weeks

Study Arms (2)

Functional Electric Stimulation cycling

ACTIVE COMPARATOR

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

Device: Functional Electric Stimulation cycling

Passive Cycling

SHAM COMPARATOR

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

Device: Passive cycling

Interventions

Functional Electric Stimulation cycling 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.

Also known as: RT300 ergometer

Functional Electric Stimulation cycling

Passive cycling 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.

Also known as: RT300 ergometer

Passive Cycling

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hugo W. Moser Research Institute at Kennedy Krieger, Inc.: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Kennedy Krieger Institute, International Center for Spinal Cord Injury

Baltimore, Maryland, 21205, United States

Location

Related Publications (4)

• 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.

  PMID: 29255645 BACKGROUND

• 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.

  PMID: 28687517 BACKGROUND

• 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.

  PMID: 26517540 BACKGROUND

• 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.

  PMID: 23805087 BACKGROUND

MeSH Terms

Conditions

Spinal Cord Injuries

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Results Point of Contact

• Title: Ann S. Choe, Ph.D.
• Organization: Kennedy Krieger Institute

choea@kennedykrieger.org

443-923-9500

Study Officials

• Ann S Choe, Ph.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 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.

Study Record Dates

• First Submitted: January 22, 2019
• First Posted: February 26, 2019
• Study Start: August 1, 2019
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: March 10, 2025
• Results First Posted: March 10, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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.

Locations

US (1)