Effects of 4-AP on Functional SCI Recovery

NCT05447676 | Unknown Early Phase 1 DMC FDA Drug

• 2 other identifiers: STU00215984R35NS122336
• Study Type: interventional
• Target: 44
• 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 in combination of Spike-timing-dependent plasticity (STDP) stimulation and STDP stimulation with limb training.

Conditions

Spinal Cord Injury

Keywords

SCI; Neural control; 4-AP; Walking; Neuroplasticity

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 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.

• 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.

  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)

• Change in MEPs

  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.

• Change in 10-meter walk test

  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.

• Change in 6-minute walk test

  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.

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

  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.

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

  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.

Study Arms (3)

Dalfampridine (4-AP)+STDP+training

ACTIVE COMPARATOR

The effects of the functional recovery of the lower-limb muscles will be determined after 10 sessions of 4-AP, STDP stimulation and training.

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

Placebo+STDP+training

PLACEBO COMPARATOR

The effects of the functional recovery of the lower-limb muscles will be determined after 10 sessions of placebo drug, STDP stimulation and training.

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

Dalfampridine (4-AP)+STDP+training for extended sessions

EXPERIMENTAL

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.

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

Interventions

Dalfampridine DRUG

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

Also known as: 4-AP

Dalfampridine (4-AP)+STDP+training; Dalfampridine (4-AP)+STDP+training for extended sessions

Placebo drug OTHER

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.

Placebo+STDP+training

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: spike timing dependent plasticity

Dalfampridine (4-AP)+STDP+training; Dalfampridine (4-AP)+STDP+training for extended sessions; Placebo+STDP+training

Exercise training BEHAVIORAL

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

Dalfampridine (4-AP)+STDP+training; Dalfampridine (4-AP)+STDP+training for extended sessions; Placebo+STDP+training

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 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

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
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

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 A Perez, PT, PhD

  Shirley Ryan Ability Lab

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Monica A Perez, PT, PhD

CONTACT

312-238-2886; mperez04@sralab.org

Sri Ramya Vemulakonda, M.B.B.S

CONTACT

3122382993; svemulakon@sralab.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Participants will not know if they receive 4-AP or placebo over the course of the study and the investigators are also blinded except for PI (Dr. Monica Perez).
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair, Arms and Hands

Model Details: 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.

Study Record Dates

• First Submitted: June 20, 2022
• First Posted: July 7, 2022
• Study Start: June 30, 2022
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2025
• Last Updated: June 22, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)