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NCT Number: NCT06853015

Double Dose 4-AP on Functional Recovery After Spinal Cord Injury

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 twice-daily in combination of Spike-timing-dependent plasticity (STDP) stimulation and STDP stimulation with limb training.

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Key information

Age range

18 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Shirley Ryan Abilitylab

Chicago, Illinois, 60611, United States

Location status: Recruiting

Location contact

Monica Perez, PT, PhD

CONTACT

[email protected]

312-238-2886

About this study

Currently, 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 spasticity, increased sensation, and decreased pain. A pharmacokinetic study showed that twice-daily administration of sustained release 4-AP maintains a steadier plasma concentration. Utilizing limb training to promote recovery of motor function is enhanced by eliciting STDP in the limbs. An important strength of this aim is the combination of training and STDP, which aims to enhance the beneficial effects of motor training by promoting plasticity in the corticospinal pathway. Training effects on physiological pathways will be explored and correlated with lower limb motor function. We hypothesize that introducing 4-AP into the STDP stimulation and STDP stimulation with training will further improve motor function rehabilitation in patients with chronic SCI.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Male and females between ages 18-85 years
  • SCI 6 months post injury
  • Spinal Cord injury at or above L2
  • ASIA A, B, C, or D, complete or incomplete
  • The ability to perform a small visible contraction with dorsiflexion and hip flexor muscles

Exclusion criteria

  • Uncontrolled medical problems including pulmonary, cardiovascular or orthopedic disease
  • Any history of renal impairment
  • Any debilitating disease prior to the SCI that caused exercise intolerance
  • Premorbid, ongoing major depression or psychosis, altered cognitive status
  • History of head injury or stroke
  • Vascular, traumatic, tumoral, infectious, or metabolic lesion of the brain, even without history of seizure, and without anticonvulsant medication
  • History of seizures or epilepsy
  • Receiving drugs acting primarily on the central nervous system, which lower the seizure threshold (see appendix 2)
  • Pregnant females
  • If a women of child bearing age is unsure of the pregnancy, and does not want to take the pregnancy test
  • Ongoing cord compression or a syrinx in the spinal cord or who suffer from a spinal cord disease such as spinal stenosis, spina bifida, MS, or herniated disk
  • Metal plate in skull
  • Individuals with scalp shrapnel, cochlear implants, or aneurysm clips
  • Individuals taking Bupropion, Dolutegravir, Lacosamide, Trilaciclib, or PR Interval prolonging drugs

Treatment and study plan

Dalfampridine

Drug

The study drug (4-AP) will be administered as a 10 mg dose twice a day.

Placebo

Drug

The placebo provided by the SRAL pharmacy that looks identical to the 4-AP, will be administered twice a day.

STDP stimulation

Other

Paired stimulation will be given to the spinal cord and to peripheral nerves so that the signals are received at the spinal cord at a specific interval.

Other names: Hebbian stimulation, spike timing dependent plasticity

Exercise Training

Behavioral

Lower-limb exercises will involve over-ground walking, treadmill, walking and stair climbing training.

Primary outcomes

  1. Change in TMEPs

    Time frame: TMEPs measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).

    Electrical stimulation will be performed placing the cathode on the upper thoracic between the spinal processes between T3 and T4 vertebrae and the anode at ~10 cm above

  2. Change in MVC

    Time frame: MVC measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).

    Individuals will perform a maximum voluntary contraction (MVC) of each targeted muscle (quadriceps femoris, tibialis anterior or soleus) through surface electrodes secured to the skin over the belly of each muscle. Ankle flexion torque will be measured by measured by force sensors.

Secondary outcomes

  1. Change in 10-meter walk test

    Time frame: 10-m walk measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).

    We will use the 10-meter walk test to quantify walking speed in meters per second. The same percentage of body-weight support will be used during pre- and post-assessments. Less time to walk 10-meter indicates better outcome.

  2. Change in 6-minute walk test

    Time frame: 6-min walk measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).

    We will measure the distance walked over 6 minutes. The same percentage of body-weight support will be used as in 10-meter walk test. The longer distance walked during 6 minutes indicates better outcome.

  3. Change in International Standards for Neurological Classification of Spinal Cord Injury exam

    Time frame: Scores measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).

    Motor part of the exam is completed through the testing of key muscle functions corresponding to 10 myotomes (C5-T1 and L2-S1) for right and left side separately. The strength of each muscle function is graded on a six-point scale ranging from 0 meaning complete paralysis to 5 meaning full strength. The total motor score is sum of all motor scores range from 0-100. Sensory part of the exam is completed through the testing of a key point in each of the 28 dermatomes (from C2 to S4-5) on the right and left sides of the body. At each of these key points, two aspects of sensation are examined: light touch and pin prick. Appreciation of light touch and pin prick sensation at each of the key points is separately scored on a three-point scale; 0-absent, 1-altered, and 2-normal or intact. 56 is the maximum score for both light touch and pin prick and the total sensory score ranges from 0 to 112. Higher scores represent better outcome for motor and sensory scores.

  4. Change in EPT

    Time frame: EPT will be measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).

    We use electrical perceptual threshold (EPT) to measures the minimum amount of electrical current that the participant can perceive when applied to the lower limb dermatomes (L2-S2).

  5. Change in surveys on ambulation, basic mobility, bowel and bladder management difficulties

    Time frame: SCI-QOL measured at at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).

    The name of the questionnaire is Spinal Cord Injury Quality of Life (SCI-QOL) and we used four subdomains: ambulation, self-care, bowel management difficulties, and bladder management difficulties. Scores on all subdomains of SCI-QOL use a standardized T metric, with a mean of 50 and a standard deviation of 10. Ambulation and basic mobility subdomains assess the ability to engage in walking activities in different locations that vary based on speed, time and condition and the ability to manage stairs under different conditions. Bowel management difficulties subdomain measures an ability to carry out a bowel program; concerns about incontinence and bowel accidents; and the impact of bowel management on everyday living. Bladder management difficulties subdomain measures ability to carry out a bladder program; worry about bladder accidents; concerns about implementing one's bladder program; and impact on everyday living. Higher scores on all subdomains represent better outcome.

  6. Change in morphological characterization of corticospinal and reticulospinal pathways in MRI

    Time frame: MRI measured at baseline, and at 12 weeks (post 40 sessions).

    In order to identify descending motor tract, brainstem and C2 cervical spinal cord images will be acquired on a MAGNETOM Prisma 3T system using a 64-channel birdcage head/neck coil. To quantify the effect of atrophy in oblique directions, we will measure the radius from the cord shape center of mass to its border, R(α), for angles α over the whole circle with an angular resolution of 6°. Mean measures of all 5 axial slices will be used for statistical from nerve roots, noise, and other confounding effects.

Other outcomes

  1. Changes in spinal excitability

    Time frame: Changes in spinal excitability will be measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).

    We will measure spinal excitability by measuring F-wave and H-reflex in soleus and TA muscles. Post-Activation Depression (PAD) of the H-reflex will also be quantified in soleus muscle

Study contacts

Contact information is provided by the study sponsor or research team.

Bing Chen, PhD

CONTACT

[email protected]

312-238-7895

Monica Perez, PT, PhD

CONTACT

[email protected]

312-238-2886

Sponsors and collaborators

Lead sponsor

Shirley Ryan AbilityLab

Other

Registry information

Official study title

Effects of Twice-daily Dosing 4-AP on Functional Recovery After Spinal Cord Injury

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Feb 28, 2025
Registry last updated
Jun 3, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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