Effects of 4-AP on Functional SCI Recovery

NCT ID: NCT05447676

Last Updated: 2023-06-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

EARLY_PHASE1

Total Enrollment

44 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-30

Study Completion Date

2025-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Spinal Cord Injury

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors
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).

Study Groups

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Dalfampridine (4-AP)+STDP+training

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

Group Type ACTIVE_COMPARATOR

Dalfampridine

Intervention Type DRUG

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

STDP stimulation

Intervention Type 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.

Exercise training

Intervention Type BEHAVIORAL

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

Placebo+STDP+training

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

Group Type PLACEBO_COMPARATOR

Placebo drug

Intervention Type 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.

STDP stimulation

Intervention Type 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.

Exercise training

Intervention Type BEHAVIORAL

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

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

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.

Group Type EXPERIMENTAL

Dalfampridine

Intervention Type DRUG

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

STDP stimulation

Intervention Type 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.

Exercise training

Intervention Type BEHAVIORAL

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

Interventions

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Dalfampridine

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

Intervention Type DRUG

Placebo drug

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.

Intervention Type OTHER

STDP stimulation

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.

Intervention Type OTHER

Exercise training

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

Intervention Type BEHAVIORAL

Other Intervention Names

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4-AP spike timing dependent plasticity

Eligibility Criteria

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Inclusion Criteria

* 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

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Shirley Ryan AbilityLab

OTHER

Sponsor Role lead

Responsible Party

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Monica Perez

Chair, Arms and Hands

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Monica A Perez, PT, PhD

Role: PRINCIPAL_INVESTIGATOR

Shirley Ryan Ability Lab

Locations

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Shirley Ryan Abilitylab

Chicago, Illinois, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Monica A Perez, PT, PhD

Role: CONTACT

312-238-2886

Sri Ramya Vemulakonda, M.B.B.S

Role: CONTACT

3122382993

Other Identifiers

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R35NS122336

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STU00215984

Identifier Type: -

Identifier Source: org_study_id

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