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Spinal Cord InjuryEarly Phase 1NCT05447676

Effects of 4-AP on Functional SCI Recovery

A Early Phase 1 study testing Dalfampridine, STDP stimulation and Exercise training in people with Spinal Cord Injury, run by Shirley Ryan AbilityLab at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Spinal Cord Injury
What is being tested?
Dalfampridine, STDP stimulation and Exercise training
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
26 participants
Where
1 siteUnited States
Study dates
30 Jun 2022to 30 Jun 2025
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male and females between ages 18-85 years
  • SCI at least 4 weeks post injury
  • Spinal Cord injury at or above L2
  • ASIA A,B,C, or D, complete or incomplete
  • Possess the following abilities
  • The ability to perform a small visible contraction with dorsiflexion and hip flexor muscles

Who cannot join

  • 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
Show all 13Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Shirley Ryan Abilitylab

    Chicago, Illinois, 60611

Other trials in United States

About this study

Official title: Effects of 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 in combination of Spike-timing-dependent plasticity (STDP) stimulation and STDP stimulation with limb training.

Read the detailed description

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. 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 at enhancing the beneficial effects of motor training by promoting plasticity in the corticospinal pathway. We hypothesize that introducing 4-AP into the STDP stimulation and STDP stimulation with lower-limb training will further improve motor function rehabilitation in patients with chronic SCI.

Being tested
Dalfampridine, Placebo drug, STDP stimulation, Exercise training
Keywords
SCI, Neural control, 4-AP, Walking, Neuroplasticity
Medical subject headings
Spinal Cord Injuries

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DalfampridineDrug

    Also called 4-AP

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

  • Placebo drugOther

    The pharmacy will also provide a placebo drug that looks identical to 4-AP to verify participants and therapists do not know who is receiving the drug and who is receiving the placebo.

  • STDP stimulationOther

    Also called spike timing dependent plasticity

    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.

  • Exercise trainingBehavioural

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

Study groups in NCT05447676
Study groupRoleWhat they receive
Dalfampridine (4-AP)+STDP+trainingActive comparatorThe effects of the functional recovery of the lower-limb muscles will be determined after 10 sessions of 4-AP, STDP stimulation and training.
Receives: Drug: Dalfampridine; Other: STDP stimulation; Behavioral: Exercise training
Placebo+STDP+trainingPlacebo comparatorThe effects of the functional recovery of the lower-limb muscles will be determined after 10 sessions of placebo drug, STDP stimulation and training.
Receives: Other: Placebo drug; Other: STDP stimulation; Behavioral: Exercise training
Dalfampridine (4-AP)+STDP+training for extended sessionsExperimentalThe 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.
Receives: Drug: Dalfampridine; Other: STDP stimulation; Behavioral: Exercise training

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in TMEPs

    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

    Measured: TMEPs measured at baseline and 3 weeks (10 sessions) for Dalfampridine+STDP+training and Placebo+STDP+training groups. TMEPs measured at baseline, 6 weeks (20 sessions), and 12 weeks (40 sessions) for extended sessions group.

  2. Change in MVC

    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.

    Measured: MVC measured at baseline and 3 weeks (10 sessions) for Dalfampridine+STDP+training and Placebo+STDP+training groups. MVC measured at baseline, 6 weeks (20 sessions), and 12 weeks (40 sessions) for extended sessions group.

Secondary outcomes (6)

  1. Change in MEPs

    Transcranial magnetic stimuli (TMS) will be delivered to the optimal scalp position for activation of quadriceps femoris and tibialis anterior muscles. The optimal scalp position will be determined by moving the coil in small steps along the hand/arm/leg representation of the primary motor cortex to find the region where the largest MEP can be evoked with the minimum intensity in the targeted muscles.

    Measured: MEPs measured at baseline and 3 weeks (10 sessions) for Dalfampridine+STDP+training and Placebo+STDP+training groups. MEPs measured at baseline, 6 weeks (20 sessions), and 12 weeks (40 sessions) for extended sessions group.

  2. Change in 10-meter walk test

    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.

    Measured: 10-m walk measured at baseline and 3 weeks (10 sessions) for Dalfampridine+STDP+training and Placebo+STDP+training groups. 10-m walk measured at baseline, 6 weeks (20 sessions), and 12 weeks (40 sessions) for extended sessions group.

  3. Change in 6-minute walk test

    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.

    Measured: 6-min walk measured at baseline and 3 weeks (10 sessions) for Dalfampridine+STDP+training & Placebo+STDP+training groups. 6-min walk measured at baseline, 6 weeks (20 sessions), and 12 weeks (40 sessions) for extended sessions group.

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

    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.

    Measured: Scores measured at baseline and 3 weeks (10 sessions) for Dalfampridine+STDP+training and Placebo+STDP+training groups. Scores measured at baseline, 6 weeks (20 sessions), and 12 weeks (40 sessions) for extended sessions group.

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

    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.

    Measured: SCI-QOL measured at baseline and 3 weeks (10 sessions) for Dalfampridine+STDP+training & Placebo+STDP+training groups. SCI-QOL measured at baseline, 6 weeks (20 sessions), and 12 weeks (40 sessions) for extended sessions group.

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

    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.

    Measured: MRI measured at baseline and 12 weeks (40 sessions) for Dalfampridine+STDP+training for extended sessions group.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jul 2022
  2. Study start30 Jun 2022
  3. Primary completion30 Jun 2024
  4. Study completion30 Jun 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
Arm 1 and 2 will be studied with randomized crossover design; Participants for Arm 3 will be recruited after finishing the sessions for Arms 1 and 2. Participants who were finished the Arms 1 and 2 study procedures can also participate in Arm 3 study procedures.
Masking
Triple blind
Who is masked
Participant, Care provider, Outcomes assessor
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05447676
Sponsor's protocol ID
STU00215984
Other IDs
R35NS122336
Status last verified
Jun 2026
First submitted
20 Jun 2022
Last updated
3 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Dalfampridine, STDP stimulation and Exercise training in people with Spinal Cord Injury, run by Shirley Ryan AbilityLab at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in TMEPs (time frame: TMEPs measured at baseline and 3 weeks (10 sessions) for Dalfampridine+STDP+training and Placebo+STDP+training groups. TMEPs measured at baseline, 6 weeks (20 sessions), and 12 weeks (40 sessions) for extended sessions group.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05447676.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2026.

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