Dalfampridine for Spinal Cord Injury

Overseen By Bing Chen, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Shirley Ryan AbilityLab

Must be taking: Dalfampridine

Must not be taking: Bupropion, Dolutegravir

Disqualifiers: Renal impairment, Major depression, Seizures, others

Compensation: Varies

Number of Visits: 40

Duration: 12 weeks

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if Dalfampridine, combined with specific physical stimulation and training, can improve leg function in individuals with spinal cord injuries. Participants will receive either the medication or a placebo (a non-active substitute) twice daily, along with exercises and stimulation sessions. Ideal participants have had a spinal cord injury for at least six months and can make small movements in their hips or feet. As a Phase 1, Phase 2 trial, this research seeks to understand the treatment's mechanism and measure its effectiveness in an initial, smaller group, offering participants the opportunity to contribute to groundbreaking advancements in spinal cord injury treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically Bupropion, Dolutegravir, Lacosamide, Trilaciclib, or drugs that prolong the PR Interval. If you are on any of these, you would need to stop them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that Dalfampridine, also known as 4-AP, is safe for humans. Research indicates it is generally well-tolerated, with mild to moderate side effects such as temporary dizziness or nausea. The FDA has already approved Dalfampridine for treating multiple sclerosis, suggesting its safety for human use. This prior approval offers reassurance about its safety, even as it undergoes testing for aiding spinal cord injury recovery. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for spinal cord injury?

Unlike the standard treatments for spinal cord injury that primarily focus on rehabilitation and managing symptoms, Dalfampridine offers a novel approach by enhancing nerve signal conduction. Researchers are excited because it targets the potassium channels in nerve fibers, potentially improving the communication between nerves and muscles. This could lead to better functional recovery in lower-limb muscles, offering hope for faster and more effective improvements in mobility compared to existing therapies.

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

This trial will evaluate the effects of Dalfampridine (4-AP) on people with spinal cord injuries (SCI). Studies have shown that Dalfampridine can potentially improve movement and sensation in those with long-term SCI. Some research suggests that 4-AP might also reduce muscle stiffness, a common issue in SCI, although its effectiveness for this remains debated. Participants in this trial will receive either Dalfampridine or a placebo, alongside STDP stimulation and training, to assess the functional recovery of lower-limb muscles. Although previous studies have shown promising results, more research is needed to consistently confirm these benefits. ^{3 5 6 7 8}

Who Is on the Research Team?

Monica Perez, PT, PhD

Principal Investigator

Shirley Ryan Ability Lab

Are You a Good Fit for This Trial?

This trial is for adults aged 18-85 with spinal cord injury at or above L2, who are at least 6 months post-injury and can perform small muscle contractions in the lower limbs. It's not suitable for those with certain pre-existing conditions, seizure history, ongoing major depression/psychosis, CNS-affecting drugs usage, uncontrolled medical issues, renal impairment, brain lesions or pregnancy.

Inclusion Criteria

SCI 6 months post injury

My spinal cord injury is at or above the L2 level.

I can slightly move my toes upwards and bend my hip.

Exclusion Criteria

I had a condition before my spinal cord injury that made it hard for me to exercise.

I do not have major depression, psychosis, or cognitive issues.

I have a history of seizures or epilepsy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive twice-daily dosing of 4-AP or placebo, combined with STDP stimulation and limb training for functional recovery of lower-limb muscles

12 weeks

40 sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dalfampridine

Trial Overview The study tests a combination treatment to improve lower limb function after SCI. Participants will receive Dalfampridine (4-AP) twice daily along with STDP stimulation and exercise training. The effectiveness of this combined approach versus placebo will be evaluated.

How Is the Trial Designed?

Group I: 4-AP(AM) + STDP stimulation + training + 4-AP(PM) Experimental Treatment 3 Interventions

The effects of the functional recovery of the lower-limb muscles will be determined after 40 sessions of twice-daily-dosing 4-AP, STDP stimulation and training.

Group II: Placebo(AM) + STDP stimulation + training + Placebo(PM) Placebo Group 3 Interventions

The effects of the functional recovery of the lower-limb muscles will be determined after 40 sessions of twice-daily-dosing Placebo, STDP stimulation and training.

Who Is Running the Clinical Trial?

Shirley Ryan AbilityLab

Lead Sponsor

Trials

212

Recruited

17,900+

Published Research Related to This Trial

Dalfampridine (DAL), used to improve nerve conduction in multiple sclerosis, can lead to de novo convulsive status epilepticus (CSE) in patients without a prior history of seizures, as demonstrated in three case reports.

The cases highlight the importance of monitoring for seizures in MS patients treated with DAL, even if they have no previous seizure history, indicating a potential safety concern with this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

De novo convulsive status epilepticus in patients with multiple sclerosis treated with dalfampridine. Panicucci, E., Cohen, M., Bourg, V., et al.[2020]

A total of 44,092 adverse event reports related to dalfampridine were analyzed, identifying 335 adverse event signals, with common issues including urinary tract infections and dizziness, particularly in females aged 45-65, which aligns with typical MS demographics.

New adverse event signals were discovered, including abnormal lymphocyte counts and urine test abnormalities, some of which were not previously documented, highlighting the importance of ongoing safety monitoring for dalfampridine in MS treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing safety surveillance of dalfampridine for multiple sclerosis using FDA adverse event reporting system. Xiong, R., Lei, J., Pan, S., et al.[2023]

In a study involving 21 patients with long-standing spinal cord injury, long-term administration of 4-aminopyridine (4-AP) at a dose of 30 mg/day led to significant improvements in both motor and sensory function after 3 months.

Patients taking 4-AP also experienced enhanced pulmonary function and reduced spasticity, with no significant drug toxicity observed, indicating that 4-AP is a safe treatment option for individuals with spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of 4-aminopyridine in humans with spinal cord injury: a long-term, controlled trial. Segal, JL., Pathak, MS., Hernandez, JP., et al.[2019]

Dalfampridine ER 10 mg has been shown to significantly improve walking in patients with multiple sclerosis, based on two pivotal Phase 3 clinical trials, indicating its efficacy in enhancing mobility.

The drug works by restoring conduction in damaged nerve fibers and improving neurotransmission, which helps patients achieve better walking speed and overall mobility, with good tolerability and minimal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of extended-release dalfampridine on walking ability in patients with multiple sclerosis. Hayes, KC.[2021]

Dalfampridine extended release (ER) significantly improved walking ability in patients with multiple sclerosis (MS) in three randomized trials, with a consistent mean improvement in walking speed of 25-29% compared to placebo.

The treatment was generally well tolerated, and sustained improvements in walking speed were observed for up to 2.5 years in noncomparative extensions of the phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dalfampridine extended release: in multiple sclerosis. Chwieduk, CM., Keating, GM.[2021]

In a review of 76 multiple sclerosis patients treated with dalfampridine, 5.3% experienced new positive sensory symptoms within one month, indicating a potential side effect of the medication.

The mechanism behind these symptoms may be linked to enhanced axonal conduction due to dalfampridine's action as a potassium-channel blocker, which could exacerbate existing neurological issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positive neurologic phenomena with initiation of dalfampridine for multiple sclerosis. Thaera, GM., Wingerchuk, DM., Carter, JL.[2015]

In a trial involving 12 patients with hereditary spastic paraplegia (HSP), treatment with dalfampridine for 2 weeks led to significant improvements in walking ability, as measured by the Spastic Paraplegia Rating Scale and the Multiple Sclerosis Walking Scale.

The study found no serious adverse events, suggesting that dalfampridine is a safe option for improving mobility in patients with HSP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dalfampridine in hereditary spastic paraplegia: a prospective, open study. Béreau, M., Anheim, M., Chanson, JB., et al.[2018]

Dalfampridine (Ampyra) is the only approved medication for improving walking in patients with multiple sclerosis, showing significant efficacy in clinical trials where about one-third of patients experienced improved walking speed.

While the recommended dose is 10 mg twice daily, higher doses increase the risk of seizures without providing additional benefits, highlighting the importance of careful dosing and monitoring for safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dalfampridine: a medication to improve walking in patients with multiple sclerosis. Pikoulas, TE., Fuller, MA.[2013]

In a study of 52 multiple sclerosis patients, dalfampridine significantly improved walking ability and reduced motoric and cognitive fatigue within just 2 weeks of treatment, with these benefits lasting up to 9-12 months.

After 9-12 months, improvements in cognitive function, specifically measured by the PASAT test, were also observed, indicating that dalfampridine has both short- and long-term positive effects on mobility and cognitive performance in MS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effects of dalfampridine in patients with multiple sclerosis. Ruck, T., Bittner, S., Simon, OJ., et al.[2022]

Dalfampridine (DAP) significantly improves mobility disability in patients with Multiple Sclerosis, as shown in a meta-analysis of 10 studies involving 2100 patients, with a notable increase in mobility speed during the Timing 24 Minute Walk Test.

The safety profile of DAP is favorable, with no significant increase in adverse events or urinary tract infections compared to placebo, particularly at doses of 10 mg or less, indicating it is a reliable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study on Dalfampridine in the treatment of Multiple Sclerosis Mobility Disability: A meta-analysis. Shi, J., Wu, X., Chen, Y.[2020]

Dalfampridine is an effective treatment for improving walking speed in patients with multiple sclerosis by blocking potassium channels on demyelinated neurons, which enhances electrical conduction.

The recommended dosage is 10 mg taken orally twice daily, but it is not suitable for patients with a history of seizures or moderate-to-severe renal impairment due to safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dalfampridine: a new agent for symptomatic management of multiple sclerosis. McDonald, S., Clements, JN.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9744758/

Functional improvement in individuals with chronic spinal cord ... This review confirms the efficacy of 4-AP in improving several conditions resulting from SCI but further research on this topic is warranted.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6241229/

Effectiveness of 4-Aminopyridine for the Management ... Conclusion: There is weak evidence supporting the effectiveness of 4-AP in reducing spasticity post SCI. Future research should utilize contemporary measures of ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05447676

NCT05447676 | Effects of 4-AP on Functional SCI Recovery Research has shown that 4-AP has a positive effect on sensory and motor function rehabilitation in humans with chronic SCI in addition to decreasing recorded ...

4. archives-pmr.org archives-pmr.org/article/S0003-9993(17)31001-8/fulltext

The Effectiveness of 4-Aminopyridine for The Management ... There is conflicting evidence regarding the effectiveness of oral and intravenous 4-AP in managing spasticity after SCI. However, it should be noted that ...

5. accpjournals.onlinelibrary.wiley.com accpjournals.onlinelibrary.wiley.com/doi/10.1592/phco.23.7.823.32731

Efficacy and Safety of 4‐Aminopyridine in Patients with Long ... The results from the first 12 weeks were used to test efficacy. Positive gains in motor function, sensation, and independence occurred more ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/10391417/

Safety and efficacy of 4-aminopyridine in humans with ... 4-Aminopyridine appears to be safe and relatively free from toxicity when administered orally over 3 months. Each patient who received immediate-release 4-AP 30 ...

7. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.1034730/full

Functional improvement in individuals with chronic spinal ... Of the 10 articles included in this review, eight secondarily evaluated 4-AP safety and identified mild-to-moderate adverse events; few articles ...

8. nature.com nature.com/articles/3101653

Effect of 4-aminopyridine on gait in ambulatory spinal cord ... Animal and human research have shown that the drug 4-aminopyridine (4-AP) may improve gait in spinal cord lesions by enhancing nerve transmission to affected ...