44 Participants Needed

Dalfampridine + Stimulation/Exercise for Spinal Cord Injury

SR
MA
Overseen ByMonica A Perez, PT, PhD
Approved in 2 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test a strategy to potentiate functional recovery of lower limb motor function in individuals with spinal cord injury (SCI). The FDA approved drug, Dalfampridine (4-AP). 4-AP will be used in combination of Spike-timing-dependent plasticity (STDP) stimulation and STDP stimulation with limb training.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically those acting on the central nervous system that lower the seizure threshold, as well as Bupropion, Dolutegravir, Lacosamide, Trilaciclib, or PR Interval prolonging drugs.

What data supports the effectiveness of the drug Dalfampridine for spinal cord injury?

Research shows that 4-aminopyridine (4-AP), the active ingredient in Dalfampridine, may improve walking and nerve function in people with spinal cord injuries. Additionally, Dalfampridine has been shown to improve walking speed in patients with multiple sclerosis, suggesting its potential to help with similar issues in spinal cord injury.12345

Is the combination of Dalfampridine and exercise safe for humans?

Dalfampridine, also known as 4-aminopyridine, has been studied for safety in people with multiple sclerosis and spinal cord injury. It is generally well tolerated, but side effects can include urinary tract infections, insomnia, headache, dizziness, and in rare cases, seizures. Exercise and physical activity are generally safe and beneficial for most people, but it's important to consult with a healthcare provider before starting any new treatment or exercise program.35678

How is the drug dalfampridine unique for treating spinal cord injury?

Dalfampridine is unique because it is a potassium channel blocker that helps improve nerve signal conduction, which can enhance walking ability in patients with spinal cord injury. It is also used in multiple sclerosis for similar purposes, making it a novel approach for spinal cord injury treatment.156910

Research Team

Richard L. Lieber, PhD

Monica Perez, PhD

Principal Investigator

Shirley Ryan Ability Lab

Eligibility Criteria

This trial is for men and women aged 18-85 with spinal cord injury (SCI) at or above L2, who are at least 4 weeks post-injury. They must be able to slightly move their hip flexor or dorsiflexion muscles. Excluded are those with a history of head injury, stroke, seizures, epilepsy, renal impairment, certain medication use (affecting the CNS), metal in the skull, uncontrolled medical issues, pre-existing debilitating diseases or mental health conditions.

Inclusion Criteria

My spinal cord injury happened over 4 weeks ago.
I am between 18 and 85 years old.
My spinal cord injury is at or above the L2 level.
See 2 more

Exclusion Criteria

I am currently taking Bupropion, Dolutegravir, Lacosamide, Trilaciclib, or drugs that prolong the PR Interval.
I am a woman of childbearing age unsure about being pregnant and refuse a pregnancy test, or I have a spinal cord condition.
I have had a head injury or stroke in the past.
See 10 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Dalfampridine (4-AP) combined with STDP stimulation and limb training for functional recovery of lower-limb muscles

3 weeks (10 sessions) for standard groups, 12 weeks (40 sessions) for extended sessions group

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

  • Dalfampridine
  • Exercise training
  • Placebo drug
  • STDP stimulation
Trial OverviewThe study tests Dalfampridine (FDA approved drug) combined with STDP stimulation and limb training to enhance lower limb motor function recovery in SCI patients. Participants will receive either this combination therapy or a placebo alongside exercise training to compare effectiveness.
Participant Groups
3Treatment groups
Experimental Treatment
Active Control
Placebo Group
Group I: Dalfampridine (4-AP)+STDP+training for extended sessionsExperimental Treatment3 Interventions
The long-term effects of the functional recovery of the lower-limb muscles will be determined after 40 sessions of 4-AP, STDP stimulation and training.
Group II: Dalfampridine (4-AP)+STDP+trainingActive Control3 Interventions
The effects of the functional recovery of the lower-limb muscles will be determined after 10 sessions of 4-AP, STDP stimulation and training.
Group III: Placebo+STDP+trainingPlacebo Group3 Interventions
The effects of the functional recovery of the lower-limb muscles will be determined after 10 sessions of placebo drug, STDP stimulation and training.

Dalfampridine is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Ampyra for:
  • Improvement of walking in adults with multiple sclerosis
🇪🇺
Approved in European Union as Fampyra for:
  • Improvement of walking in adults with multiple sclerosis

Find a Clinic Near You

Who Is Running the Clinical Trial?

Shirley Ryan AbilityLab

Lead Sponsor

Trials
212
Recruited
17,900+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials
1,403
Recruited
655,000+

Findings from Research

In a study involving 20 patients with chronic, incomplete spinal cord injury, 4-aminopyridine (4-AP) did not show significant improvements in functional status or walking speed after four weeks of treatment.
While there was a statistically significant effect on vibration perception threshold in the left fingers, patients treated with 4-AP actually experienced a less favorable response compared to those on placebo, indicating no overall benefit from the drug.
Randomized trial of 4-aminopyridine in patients with chronic incomplete spinal cord injury.van der Bruggen, MA., Huisman, HB., Beckerman, H., et al.[2019]
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.
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]
In a study of 27 patients with long-term spinal cord injury, those treated with 4-aminopyridine (4-AP) showed significant improvements in motor function (92% vs. 46% for placebo) and overall sensorimotor changes, indicating its efficacy as a treatment.
The drug was found to be generally safe, with 56% of patients experiencing mild to moderate adverse reactions, including one case of posterior tibial artery vasospasm, highlighting the need for careful monitoring during treatment.
Efficacy and safety of 4-aminopyridine in patients with long-term spinal cord injury: a randomized, double-blind, placebo-controlled trial.Grijalva, I., Guízar-Sahagún, G., Castañeda-Hernández, G., et al.[2019]

References

Randomized trial of 4-aminopyridine in patients with chronic incomplete spinal cord injury. [2019]
Safety and efficacy of 4-aminopyridine in humans with spinal cord injury: a long-term, controlled trial. [2019]
Efficacy and safety of 4-aminopyridine in patients with long-term spinal cord injury: a randomized, double-blind, placebo-controlled trial. [2019]
Effect of 4-aminopyridine on gait in ambulatory spinal cord injuries: a double-blind, placebo-controlled, crossover trial. [2013]
Development of dalfampridine, a novel pharmacologic approach for treating walking impairment in multiple sclerosis. [2014]
Pharmacokinetics and safety of multiple oral doses of sustained-release 4-aminopyridine (Fampridine-SR) in subjects with chronic, incomplete spinal cord injury. [2019]
Extended-release dalfampridine in the management of multiple-sclerosis-related walking impairment. [2021]
Dalfampridine: review of its efficacy in improving gait in patients with multiple sclerosis. [2021]
Pharmacokinetics of 14C-radioactivity after oral intake of a single dose of 14C-labeled fampridine (4-aminopyridine) in healthy volunteers. [2014]
Intrathecal administration of 4-aminopyridine in chronic spinal injured patients. [2019]