Enhancing Corticospinal Excitability to Improve Functional Recovery

Spinal Cord Injuries Clinical Trial

Official title:

Enhancing Corticospinal Excitability to Improve Functional Recovery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03237091
• Other study ID #: 723
• Status: Completed
• Phase: N/A
• Start date: May 3, 2018
• Est. completion date: September 27, 2019

Study information

• Verified date: October 2019
• Source: Shepherd Center, Atlanta GA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Research indicates that increasing brain excitability might help improve hand function in people with spinal cord injury. Brain stimulation that uses electrodes placed on the surface of the scalp (also called "non-invasive brain stimulation") increases brain excitability and has the potential to make it easier for the brain and nervous system to respond to arm and hand training. The purpose of this study is to compare four different types of stimulation for increasing brain excitability to determine which types are best for helping people with tetraplegia improve their ability to use their arms and hands. To fully evaluate the value of brain stimulation on arm and hand function, the investigators will also evaluate the effect of sham (fake) stimulation. Each participant will receive a single session of each of the five types of stimulation being tested.

Description:

Restoration of upper extremity function is often the top rehabilitation goal for persons who have sustained a cervical spinal cord injury (SCI). Following SCI, beyond the disruption caused by the injury itself, maladaptive cortical reorganization further limits descending corticospinal drive. Therefore, therapies aimed at increasing the descending drive provided by corticospinal and other descending supraspinal tracts could be beneficial adjuncts to commonly used rehabilitation therapies. While many rehabilitation research strategies for improving function following SCI target the spinal circuitry, relatively few rehabilitative approaches are directed toward promoting supraspinal neuroplasticity to reduce impairment by increasing volitional control. Spectacular high-tech interventions and elegant high-tech outcome measures generate a great deal of excitement in the scientific world. However, the technological investment and training required for these approaches and the questionable clinical meaningfulness of the outcomes is a major limitation to their real-world value.

Transcranial direct current stimulation (tDCS) is a clinically accessible form of non-invasive brain stimulation (NIBS) that has been shown to improve upper extremity function in persons with SCI. Clinical accessibility and the potential for prolonged modulation of cortical excitability make tDCS is an attractive tool for non-invasive modulation of corticospinal excitability.

Beyond traditional tDCS, intriguing recent studies in non-disabled individuals suggest a novel form of NIBS, transcranial pulsed current stimulation (tPCS), may be more effective for inducing changes in corticospinal excitability. tPCS utilizes unidirectional, positive pulses of current separated by brief interpulse intervals rather than continuous direct current. Some evidence from our lab and others indicates that patterned stimulation has a larger influence on neural excitability than uniform stimulation.

Importantly, the efficacy of NIBS is dependent upon stimulation site. Since persons with tetraplegia have bimanual impairments, it has been suggested that bihemispheric anodal (excitatory) tDCS may be of value. Bihemispheric anodal tDCS has been studied in non-disabled individuals; this approach was found to be safe and was associated with improved bimanual control. However, the value of this approach has not previously been assessed in persons with tetraplegia.

The investigators propose a randomized, sham-controlled crossover study in which two forms of NIBS (tDCS and tPCS) will be compared with a sham-control intervention to determine their relative efficacy for improving upper extremity strength and motor control (Aim 1) and corticospinal excitability (Aim 2) in individuals with chronic (≥ 6 months) tetraplegia. The efficacy of two different stimulation montages, uni- and bihemispheric, will also be compared (Aim 3). Subjects will receive a single session of each NIBS condition (unihemispheric tDCS, bihemispheric tDCS, unihemispheric tPCS, bihemispheric tPCS) and a sham-control condition.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: September 27, 2019
• Est. primary completion date: September 27, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Cervical (neurological level C1-C8) SCI occurring more than 6 months ago

• Any severity classification (ASIA/ISNCSCI A, B, C, D)

• Self-reported functional limitation in at least one upper limb

• Ability to voluntarily move thumb or index finger (visible twitch) of both upper limbs

• Ability and willingness to consent to participate in the study and authorize use of protected health information

Exclusion Criteria:

• Pacemaker or metal implant in the head

• History of seizure

• History of frequent or severe headaches

• Damage to the nerves of the arms/hands (lower motor neuron damage) as documented in medical record, per participant report, or during in-person screening

• Prior tendon or nerve transfer surgery

• Severe pain or hypersensitivity of the arm/hand that would limit participation in arm and hand training

• Severe contractures of the arm/hand that would limit participation in arm and hand training

• Current pregnancy

Related Conditions & MeSH terms

• Quadriplegia
• Spinal Cord Injuries
• Tetraplegia

Intervention

Other:
• bihemispheric transcranial pulsed current stimulation (tPCS)
Two sets of sponge electrodes (one set placed on each side of the head) will be placed on the participant's head. The transcranial electrical stimulator will apply unidirectional, positive pulses of current separated by brief interpulse intervals to the scalp via the sponges for 30 minutes.
• unihemispheric transcranial pulsed current stimulation (tPCS)
One set of sponge electrodes will be placed on the participant's head. The transcranial electrical stimulator will apply unidirectional, positive pulses of current separated by brief interpulse intervals to the scalp via the sponges for 30 minutes.
• bihemispheric transcranial direct current stimulation (tDCS)
Two sets of sponge electrodes (one set placed on each side of the head) will be placed on the participant's head. The transcranial electrical stimulator will apply continuous, direct current to the scalp via the sponges for 30 minutes.
• unihemispheric transcranial direct current stimulation (tDCS)
One set of sponge electrodes will be placed on the participant's head. The transcranial electrical stimulator will apply continuous, direct current to the scalp via the sponges for 30 minutes.
• sham-control
Sponge electrodes will be placed on the participant's head. The transcranial electrical stimulator will apply stimulation to the scalp via the sponges for 1-2 minutes. The stimulator will then be turned off.

Locations

Country	Name	City	State
United States	Shepherd Center	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Shepherd Center, Atlanta GA	The Craig H. Neilsen Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline Motor Control & Strength	The motor control outcome measure evaluates how quickly the participant can move their fingers. Participants will tap their thumb or index finger as fast as possible for 10 seconds at a time while a sensor counts the number of taps. The strength outcome measure evaluates the participant's hand strength. Participants will use their thumb and index finger to pinch a hand-held device that measures their strength.	Through study completion, up to 5 weeks
Primary	Change from Baseline Corticospinal Excitability	This outcome measure evaluates communication between the participant's brain and spinal cord. The skin over the muscles of both arms and hands will be cleaned with an alcohol swab and a mildly abrasive paste (similar to the feel of toothpaste). Sensors that detect muscle activity will be placed over these sites. Pulses of stimulation will be applied to the participant's head using a type of non-invasive brain stimulation called transcranial magnetic stimulation (TMS). This stimulation will activate the brain regions that control arm and hand movement. The strength of the stimulation will be increased until it causes the muscles of the arm and hand to twitch, and the size of the muscle response will be recorded with the sensors placed over the muscles.	Through study completion, up to 5 weeks
Secondary	Stimulation Questionnaire	This outcome measure evaluates the participant's perception of stimulation.	Through study completion, up to 5 weeks