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

NCT06853015 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STU00221545
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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). 4-AP will be used twice-daily in combination of Spike-timing-dependent plasticity (STDP) stimulation and STDP stimulation with limb training.

Conditions

SCI - Spinal Cord Injury

Keywords

spinal cord injury; neurostimulation; 4-AP; rehabilitation

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  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

  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

  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

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

• Change in EPT

  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

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

Other Outcomes (1)

• Changes in spinal excitability

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

Study Arms (2)

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.

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.

Drug: Placebo; Other: STDP stimulation; Behavioral: Exercise training

Interventions

Dalfampridine DRUG

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

4-AP(AM) + STDP stimulation + training + 4-AP(PM)

Placebo DRUG

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

Placebo(AM) + STDP stimulation + training + Placebo(PM)

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.

Also known as: Hebbian stimulation, spike timing dependent plasticity

4-AP(AM) + STDP stimulation + training + 4-AP(PM); Placebo(AM) + STDP stimulation + training + Placebo(PM)

Exercise training BEHAVIORAL

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

4-AP(AM) + STDP stimulation + training + 4-AP(PM); Placebo(AM) + STDP stimulation + training + Placebo(PM)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shirley Ryan AbilityLab: lead

Study Sites (1)

Shirley Ryan Abilitylab

Chicago, Illinois, 60611, United States

RECRUITING

MeSH Terms

Conditions

Spinal Cord Injuries

Interventions

4-Aminopyridine; Exercise

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Aminopyridines; Amines; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Monica Perez, PT, PhD

  Shirley Ryan Ability Lab

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Monica Perez, PT, PhD

CONTACT

312-238-2886; mperez04@sralab.org

Bing Chen, PhD

CONTACT

312-238-7895; bchen03@sralab.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Scientific Chair

Study Record Dates

• First Submitted: February 14, 2025
• First Posted: February 28, 2025
• Study Start: February 1, 2025
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: April 3, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)