Non-Invasive Stimulation for Improving Motor Function

Kathleen Friel

Status and phase: Active, not recruiting; Phase 2

Conditions: Spinal Cord Injuries

Treatments: Diagnostic Test: Paired TMS & Peripheral Nerve Stimulation

Study type: Interventional

Funder types: Other

Identifiers

NCT03592173

BRC391

Details and patient eligibility

About

The purpose of this study is to determine if spinal excitability is increased with a Spinal Associative Stimulation (SAS) protocol, and to determine the functional consequences of this technique on motor recovery.

Full description

Recovery of motor function continues to be a problem following Spinal Cord Injury. Non-invasive brain stimulation techniques, targeting cortical areas, have been shown to enhance the excitability in the human motor cortex, and these changes in the motor cortex may be of significance for the rehabilitation of brain injured patients. However, little is known about the adaptational changes in the excitability/plasticity of spinal neural circuits in spinal cord injury patients.

The purpose of this study is to investigate the excitability of cortical and spinal inhibitory and excitatory mechanisms before and following a period of repetitive and synchronized dual peripheral nerve and brain stimulation. Repetitive, paired brain and peripheral nerve stimulation as a neuromodulatory tool, paired associative stimulation (PAS), has been well described. In this technique, stimuli are timed such that afferent and efferent volleys interact at the level of the cortex, that lead to a temporary enhancement of Motor Evoked Potential (MEP) amplitude in target muscles, and when applied repeatedly, lead to a sustained effect, outlasting the intervention period. This repetitive technique has been done in healthy subjects and patients with neurological diseases. By modifying the time between paired stimuli, the investigators will generate afferent/efferent interactions in the spinal cord.

The working hypothesis of this study is that the acute facilitation of the H-reflex during Paired TMS and peripheral nerve stimulation, may be harnessed to modulate spinal excitability (sustained increase in the MEP amplitude). That is, the investigators will test if similar to PAS, a change in excitability outlasting the stimulation/intervention period may occur with afferent/efferent interactions, although at the level of the spinal cord rather than the cortex, and be useful to strengthen residual pathways after damage to the spinal cord.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Spinal cord injury subjects with chronic lesions (> 6 months after the injury)
• Motor incomplete lesion, measured by the American Spinal cord Injury Association (ASIA) Impairment Scale (AIS)
• Traumatic cause of lesion; d) Some degree of motor function in the ankle flexor and extensors (Low extremity Motor Score - LEMS≥3).

Exclusion criteria

• Motor and sensory complete lesion (AIS A); LEMS < 3;
• Non-traumatic cause of lesion
• Medically unstable condition
• Other concurrent neurological illness
• Presence of a potential TMS risk factor (detailed below)

Potential TMS risk factor:

• Damaged skin at the site of stimulation
• Presence of an electrically, magnetically or mechanically activated implant
• An intracerebral vascular clip, or any other electrically sensitive support system
• Metal in any part of the body, including metal injury to the eye
• A history of medication-resistant epilepsy in the family
• Past history of seizures or unexplained spells of loss of consciousness.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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30 participants in 3 patient groups

SAS20

Experimental group

Description:

The paired stimulation (SAS) will be comprised of patient adjusted subthreshold TMS (80% of resting motor threshold over optimal site for soleus muscle), delivered 20ms prior to a peripheral nerve stimulus in the popliteal fossa and will be repeated at 0.1 Hz for 15 minutes (90 stimuli pairs).

Treatment:

Diagnostic Test: Paired TMS & Peripheral Nerve Stimulation

SAS0

Active Comparator group

Description:

The paired stimulation (SAS) will be comprised of patient adjusted subthreshold TMS (80% of resting motor threshold over optimal site for soleus muscle), delivered 0ms prior to a peripheral nerve stimulus in the popliteal fossa and will be repeated at 0.1 Hz for 15 minutes (90 stimuli pairs).

Treatment:

Diagnostic Test: Paired TMS & Peripheral Nerve Stimulation

SAS50

Active Comparator group

Description:

The paired stimulation (SAS) will be comprised of patient adjusted subthreshold TMS (80% of resting motor threshold over optimal site for soleus muscle), delivered 50ms prior to a peripheral nerve stimulus in the popliteal fossa and will be repeated at 0.1 Hz for 15 minutes (90 stimuli pairs).

Treatment:

Diagnostic Test: Paired TMS & Peripheral Nerve Stimulation