Paired Associative Stimulation + Locomotor Training for Spinal Cord Injury

Overseen By Dalia De Santis

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Shirley Ryan AbilityLab

Disqualifiers: Pulmonary, cardiovascular, orthopedic, epilepsy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 10

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help individuals with spinal cord injuries (SCI) improve their walking ability. It combines special auditory and electrical stimulation, known as Paired Associative Stimulation, with regular walking exercises, referred to as Locomotor Training, to determine if it can enhance muscle strength and walking speed. The trial compares this new method to a similar routine that uses softer sounds and stimulations to assess any significant differences. Candidates include those who have had an SCI for at least six months, have some leg movement, and require assistance walking. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the research team for guidance.

What prior data suggests that this intervention is safe for individuals with spinal cord injury?

Research has shown that paired associative stimulation (PAS), when combined with movement training, is safe and practical for people with spinal cord injuries. Studies have found that high levels of PAS can be added to regular rehabilitation without major safety issues. In one study, participants receiving PAS demonstrated improved movement abilities without significant side effects, suggesting the treatment is well-tolerated.

The current trial is in its early stages, meaning the treatment is still being tested for safety in humans. While early trials mainly focus on safety and dosage, past research indicates that PAS holds promise for being both safe and effective in improving recovery. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Paired Associative Stimulation (PAS) and Locomotor Training for spinal cord injury because it's a fresh approach that combines sensory stimulation with physical training. Unlike traditional treatments that might rely solely on physical therapy or medication, this method uses loud auditory cues paired with electrical pulses to potentially enhance neural connections while patients walk on a treadmill. This innovative approach aims to boost the effectiveness of rehabilitation by directly stimulating the nervous system, offering hope for improved recovery outcomes.

What evidence suggests that this trial's treatments could be effective for spinal cord injury?

This trial will compare the effects of paired associative stimulation (PAS) combined with locomotor training to a sham intervention. Studies have shown that PAS can improve movement in people with spinal cord injuries (SCI). Research indicates that combining PAS with walking exercises can increase walking speed and muscle strength. PAS uses loud sounds and small electrical pulses to stimulate the nerves, enhancing the coordination between the brain and spinal cord for better movement. Evidence suggests this method can enhance muscle control and coordination. Overall, PAS has shown promise in aiding recovery for those with long-term SCI. ^{1 2 3 4 6}

Who Is on the Research Team?

Dalia De Santis, PhD

Principal Investigator

Shirley Ryan AbilityLab

Are You a Good Fit for This Trial?

This trial is for individuals with spinal cord injury (SCI) who've had it for at least 6 months, can stand and walk a little on a treadmill, and need some support to walk. They should be able to move their ankle slightly but have weakness in the ankle muscles. People with severe cognitive issues, recent high-intensity training, metal implants in the head, epilepsy or uncontrolled medical conditions that affect physical performance cannot join.

Inclusion Criteria

I can walk 10 meters without help.

I have had a spinal cord injury for at least 6 months.

My spinal injury is classified as moderate to mild.

Exclusion Criteria

I don't have any health issues that stop me from moving around easily.

I cannot tolerate physical activity.

I am able to understand and participate in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 10 sessions of either startle or non-startle stimulus combined with locomotor training

2 weeks

10 sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Locomotor Training
• Paired Associative Stimulation

Trial Overview The study tests if loud sounds paired with electrical muscle stimulation along with walking exercises can improve walking speed and muscle strength in people with chronic SCI. It compares this new method against sham stimulation—a fake treatment used as a control—to see which is more effective.

How Is the Trial Designed?

Group I: Locomotor training + PAS Experimental Treatment 2 Interventions

This intervention uses repeated paired loud auditory and electrical stimulation of muscle afferents combined with locomotor training. Participants will exercise walking on a treadmill with body weight support as needed for 30 minutes a day at a moderate intensity. While walking, participants will receive brief loud auditory stimuli through headphones and short electrical pulses through of electrodes positioned on two points in the leg

Group II: Locomotor training + SHAM Placebo Group 2 Interventions

This sham intervention uses repeated paired soft auditory clicks and electrical stimulation of muscle afferents combined with locomotor training. Participants will exercise walking on a treadmill with body weight support as needed for 30 minutes a day at a moderate intensity. While walking, participants will receive brief auditory clicks through headphones and short electrical pulses through a pair of electrodes positioned on two points in the leg.

Who Is Running the Clinical Trial?

Shirley Ryan AbilityLab

Lead Sponsor

Trials

212

Recruited

17,900+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1878747925002569

Paired associative stimulation improves outcomes when ... Patients with incomplete cervical SCI were randomized 1:1 within 1–4 months post-injury to receive 12 weeks of PAS or sham stimulation alongside ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5610384/

Long-Term Paired Associative Stimulation Enhances Motor ... The PAS hand improved by 0.74 ± 0.18 points (p < 0.0001, n = 100 muscles from 5 patients), whereas the PNS hand improved by 0.55 ± 0.08 points (p < 0.0001, n = ...

3. tandfonline.com tandfonline.com/doi/abs/10.1080/17434440.2024.2358048

Paired associative stimulation to enhance motor outcome ... Available evidence showed an increase in motor outcomes after PAS stimulation. Indeed, both clinical and neurophysiological outcomes suggest the effectiveness ...

4. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.1000940/full

Brain and spinal cord paired stimulation coupled with ... Our results support that targeted brain and spinal cord stimulation alters responsiveness of neurons over multiple spinal segments in people with chronic SCI.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07223710

NCT07223710 | Improving Walking After Spinal Cord Injury In this study we propose to test the effects of a novel intervention that uses repeated paired loud auditory and electrical stimulation of ...

6. journals.lww.com journals.lww.com/nrronline/fulltext/2022/11000/effects_of_paired_associative_magnetic_stimulation.32.aspx

Effects of paired associative magnetic stimulation between... The primary outcome measure of this trial is change in lower limb American Spinal Injury Association Impairment Scale motor function score from baseline to last ...