An Exercise Intervention to Reduce Neuropathic Pain and Brain Inflammation After Spinal Cord Injury

NCT04137159 | Terminated

• 1 other identifier: 2019P003113
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

Spinal Cord Injury (SCI) leads to alterations in brain structure and function by spinal nerve damage, secondary inflammatory responses, and by the consequences of living with paralysis and neuropathic pain. Physical inactivity due to lower body paralysis rapidly leads to loss of muscle, and risk of heart disease. The leading cause of death after a spinal cord injury is cardiovascular disease, and just a year after injury, those with SCI have a peak exercise capacity half that of the unfit general population. The good news is that aerobic exercise reduces the risk of chronic metabolic and cardiorespiratory diseases, reduces inflammation and pain, and increases mood and quality of life. Exercise can also reduce brain inflammation, enhance endogenous analgesia, and increases the size of the hippocampus. The issue is that muscle paralysis in SCI restricts the ability to achieve the levels of exercise that is necessary for broad analgesic, anti-inflammatory and neuroprotective benefits. Arm exercise can have some effects on heart and lung capacity, but the small muscle mass is insufficient to produce more than modest aerobic work. With functional electrical stimulation (FES), leg muscles that are paralyzed can be made to contract, thereby allowing more of the body to be exercised. The full rowing stroke is produced by both the (stimulated) legs and arms, increasing the active muscle mass and resulting in an aerobic work-out that is intensive enough to improve heart, lung, and - maybe - brain function. In this clinical trial of sub-acute spinal cord injured subjects, the investigators will study how 12 weeks of FES-RT, in comparisons to 12 weeks of wait-list, changes pain, brain structure, endogenous opioid function and brain inflammation. The investigators will measure changes using positron emission tomography and magnetic resonance imaging. The investigators hypothesize a decrease in pain interference, an increase in hippocampal volume, increased endogenous opioid transmission in the periaqueductal gray, and decreased hippocampus neuroinflammation.

Conditions

Spinal Cord Injuries

Outcome Measures

Primary Outcomes (4)

• Change in PROMIS Pain Interference questionnaire

  The Patient-Reported Outcomes Measurement Information System (PROMIS(r)) Pain Interference instrument measure the self-reported consequences of pain on relevant aspects of a person's life and may include the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities. Pain Interference also incorporates items probing sleep and enjoyment in life. The scale ranges from 6 to 30, with 30 being the highest pain interference.

  Change between baseline and after 12 week FES intervention, and after 12 week wait list

• Change in Hippocampal volume

  MRI derived measurement of hippocampus volume

  Change between baseline and after 12 week FES intervention, and after 12 week wait list

• Change in Hippocampus glial activation

  11C-PBR28 SUV uptake in the hippocampus

  Change between baseline and after 12 week FES intervention, and after 12 week wait list

• Change PAG opioid binding potential

  Non-displaceable opioid binding potential of the periaqueductal gray

  Change between baseline and after 12 week FES intervention, and after 12 week wait list

Study Arms (2)

FES rowing

EXPERIMENTAL

Exercise training sessions will be performed 3 times per week for 12 weeks. The initial training sessions will include 6 sets of FES-rowing for 5 min at 60% of VO2 peak with a work-to-rest ratio of 2:1. Participants unable to row continuously for 5 min will row for 2-4 min with 30-second breaks incorporated until they achieve sets totaling 30 min. The goal is for each volunteer to achieve an exercise intensity of 70-85% maintained for a continuous 30-40 min performed 3 times each week.

Other: Functional Electrical Stimulation rowing exercise

Wait list

NO INTERVENTION

During the 12-week treatment as usual program, subjects will not participate in FES-rowing.

Interventions

Functional Electrical Stimulation rowing exercise OTHER

Full-body aerobic exercise

FES rowing

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \* SCI at or below neurological level C5 with American Spinal Injury Association grade A, B or C, within 3-24 months after injury.

You may not qualify if:

• pregnancy
• breast feeding
• contraindications to MRI
• contraindications to PET current or past history of:
• major medical illness
• major neurological illness other than SCI
• major psychiatric illness
• diabetes
• major kidney or liver problems
• use of tobacco
• use of recreational drugs
• an abnormal physical exam (e.g., heart murmurs or peripheral edema).
• unresponsive to FES stimulation
• heart disease
• physical limitations to FES-RT success

Sponsors & Collaborators

• Spaulding Rehabilitation Hospital: lead

Study Sites (1)

Spaulding Rehabilitation Hospital

Boston, Massachusetts, 02129, United States

Location

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

Study Officials

• Nils C Linnman, PhD

  Spaulding Rehabilitation Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Study statistician is masked to intervention type
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Randomized cross-over wait-list controlled

Study Record Dates

• First Submitted: October 18, 2019
• First Posted: October 23, 2019
• Study Start: February 20, 2020
• Primary Completion: November 1, 2024
• Study Completion: November 1, 2024
• Last Updated: January 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)