SCI - Spinal Cord InjuryPhase 1/2NCT06853015
Double Dose 4-AP on Functional Recovery After Spinal Cord Injury
A Phase 1/2 study testing Dalfampridine, STDP stimulation and Exercise training in people with SCI - Spinal Cord Injury, run by Shirley Ryan AbilityLab at 1 site in United States.
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
- SCI - Spinal Cord Injury
- What is being tested?
- Dalfampridine, STDP stimulation and Exercise training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2025to 30 Dec 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 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
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 14Show 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. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Shirley Ryan Abilitylab
Chicago, Illinois, 60611
Monica Perez, PT, PhD, 312-238-2886, mperez04@sralab.org
About this study
Official title: Effects of Twice-daily Dosing 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.
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. 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.
- Conditions
- SCI - Spinal Cord Injury
- Being tested
- Dalfampridine, Placebo, STDP stimulation, Exercise training
- Keywords
- spinal cord injury, neurostimulation, 4-AP, rehabilitation
- 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
The study drug (4-AP) will be administered as a 10 mg dose twice a day.
PlaceboDrug
The placebo provided by the SRAL pharmacy that looks identical to the 4-AP, will be administered twice a day.
STDP stimulationOther
Also called Hebbian stimulation, 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 group | Role | What they receive |
|---|---|---|
| 4-AP(AM) + STDP stimulation + training + 4-AP(PM) | Experimental | 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. Receives: Drug: Dalfampridine; Other: STDP stimulation; Behavioral: Exercise training |
| Placebo(AM) + STDP stimulation + training + Placebo(PM) | Placebo comparator | 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. Receives: Drug: Placebo; Other: STDP stimulation; Behavioral: Exercise training |
What is being measured
The primary outcome is the main question the study is designed to answer.
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, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).
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. Ankle flexion torque will be measured by measured by force sensors.
Measured: MVC measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).
Secondary outcomes (6)
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, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).
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, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).
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, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).
Change in EPT
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).
Measured: EPT will be measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).
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 at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).
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 at 12 weeks (post 40 sessions).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2025
- Study start1 Feb 2025
- Primary completion1 Mar 2026
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SCI - Spinal Cord InjuryStudies of the same condition, open and under way.
- More trials run by Shirley Ryan AbilityLabThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shirley Ryan AbilityLab
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Monica Perez, Shirley Ryan AbilityLab
- Investigators
- Monica Perez, PT, PhD, Principal investigator, Shirley Ryan Ability Lab
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06853015
- Sponsor's protocol ID
- STU00221545
- Status last verified
- Jun 2026
- First submitted
- 14 Feb 2025
- Last updated
- 3 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Twice-daily Dosing 4-AP on Functional Recovery After Spinal Cord Injury
- ClinicalTrials.gov ID
- NCT06853015
- Acronym / sponsor ID
- STU00221545
- Conditions
- SCI - Spinal Cord Injury
- Keywords
- spinal cord injury, neurostimulation, 4-AP, rehabilitation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- Shirley Ryan AbilityLabUniversity, hospital or other
- Study start
- 1 Feb 2025 (actual)
- Primary completion
- 1 Mar 2026 (actual)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 28 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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. 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 4-AP(AM) + STDP stimulation + training + 4-AP(PM) | Experimental | Drug: Dalfampridine, Other: STDP stimulation, Behavioral: Exercise trainingThe 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. |
| Placebo(AM) + STDP stimulation + training + Placebo(PM) | Placebo comparator | Drug: Placebo, Other: STDP stimulation, Behavioral: Exercise trainingThe 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 may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DalfampridineThe study drug (4-AP) will be administered as a 10 mg dose twice a day. | Drug | 4-AP(AM) + STDP stimulation + training + 4-AP(PM) |
| PlaceboThe placebo provided by the SRAL pharmacy that looks identical to the 4-AP, will be administered twice a day. | Drug | Placebo(AM) + STDP stimulation + training + Placebo(PM) |
| STDP stimulationAlso: Hebbian stimulation, spike timing dependent plasticityPaired 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 | 4-AP(AM) + STDP stimulation + training + 4-AP(PM), Placebo(AM) + STDP stimulation + training + Placebo(PM) |
| Exercise trainingLower-limb exercises will involve over-ground walking, treadmill, walking and stair climbing training. | Behavioural | 4-AP(AM) + STDP stimulation + training + 4-AP(PM), Placebo(AM) + STDP stimulation + training + Placebo(PM) |
Primary outcome
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
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.
6 secondary outcomes
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).
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).
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).
Change in EPT
Time frame: EPT will be measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).
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).
Change in morphological characterization of corticospinal and reticulospinal pathways in MRI
Time frame: MRI measured at baseline, and at 12 weeks (post 40 sessions).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Monica Perez, PT, PhD principal investigator
Shirley Ryan Ability Lab
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Dalfampridine, STDP stimulation and Exercise training in people with SCI - 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 5 inclusion and 14 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: looking for participants now, 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Monica Perez, PT, PhD (312-238-2886, mperez04@sralab.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in TMEPs (time frame: TMEPs measured at baseline, at 6 weeks (post 20 sessions), and at 12 weeks (post 40 sessions).). 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?
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; AzTrials last refreshed its copy on 1 Nov 2026.