Spine and Brain Stimulation for Movement Recovery After Cervical Spinal Cord Injury

Official title

Pilot Study to Evaluate the Safety and Tolerability of Spinal Cord Stimulation (SCS) and Paired Spine And Brain Stimulation For Movement Recovery After Spinal Cord Injury (SCI)

Overview

Stimulation of the spinal cord and brain represents a new experimental therapy that may have potential to restore movement after spinal cord injury. While some scientists have begun to study the effect of electrical stimulation on patient's ability to walk and move their legs after lower spinal cord injury, the use of stimulation of the upper (cervical) spine to restore arm and hand function after cervical spinal cord injury remains less well explored. The investigators are doing this research study to improve understanding of whether cervical spinal cord stimulation and brain stimulation can be used to improve arm and hand function. To do this, the investigators will combine spine stimulation (in the form of electrical stimulation from electrical stimulation wires temporarily implanted next to the cervical spinal cord) and brain stimulation (in the form of transcranial magnetic stimulation). The investigators will perform a series of experiments over 29 days to study whether these forms of stimulation can be applied and combined to provide improvement in arm and hand function.

Detailed description

Loss of movement following spinal cord injury (SCI) often results from incomplete disruption of structures within the spinal cord, leaving some residual pathways of communication intact. Epidural spinal cord stimulation (SCS) has been used to recruit these residual communication pathways' spared circuits and restore walking in patients with leg paralysis. But SCS to improve arm and hand function remains largely unexplored, even though this is the commonest type of SCI and restoration of upper limb function is of highest priority to patients. The goal of this study is to understand the interactions between SCS and residual neural communication pathways in the brain and spine that control arm and hand function in order to restore movement after cervical SCI.

This is a pilot study in which patients with traumatic spinal cord injury will undergo temporary placement of small electronic stimulation wires near the cervical spinal cord followed by a series of experiments over 29 days focused on three main aims. In Aim 1 (mapping responses to SCS), the investigators will map patient's motor responses to SCS to identify how motor responses are affected by areas of spinal cord injury. In Aim 2 (pairing SCS with attempted motor activation and brain stimulation), the investigators will combine SCS with patient attempts to move in order to study how SCS interacts with conscious motor control and also pair SCS with brain stimulation using transcranial magnetic stimulation. Finally, in Aim 3 (therapeutic effects), the investigators seek to use SCS to change the natural electrical circuits in the spinal cord and observe changes in motor function in both the short- and long-term.

Interventions

• Device Epidural spinal cord stimulation and paired spine and brain stimulation
  The spinal cord and brain stimulator allows for stimulation of the spinal cord and brain. Spinal cord stimulation (SCS) is provided by temporarily implanted SCS catheter electrode leads (Medtronic) that are connected to an external stimulator (Digitimer); brain stimulation is provided by transcranial magnetic stimulation (TMS).

Primary outcome measures

• Serious adverse events related to the study device [Time frame: From enrollment to the end of follow up at 30 weeks]
• Cessation of spinal cord stimulation or brain stimulation due to participant request [Time frame: From enrollment to the end of follow up at 30 weeks]

Secondary outcome measures (12)

• Efficacy derived from spine-only and brain-only recruitment curves [Time frame: Compared at visit 7/8 to visit 24/25 (~end of week 2 and end of week 5)]
• Selectivity derived from spine-only and brain-only recruitment curves [Time frame: Compared at visit 7/8 to visit 24/25 (~end of week 2 and end of week 5)]
• Immediate effect of volitional motor activation combined with spinal stimulation [Time frame: Compared at visit 7/8 to visit 24/25 (~end of week 2 and end of week 5)]
• Immediate pairing effect of spine and brain stimulation [Time frame: Compared at visit 7/8 to visit 24/25 (~end of week 2 and end of week 5)]
• Lasting effects of sustained spine and brain pairing [Time frame: Compared at visit 7/8 to visit 24/25 (~end of week 2 and end of week 5)]
• Magnitude of motor evoked potentials in TMS maps [Time frame: Compared at visit 7/8 to visit 24/25 (~end of week 2 and end of week 5)]
• Size of responsive cortex in TMS maps [Time frame: Compared at visit 7/8 to visit 24/25 (~end of week 2 and end of week 5)]
• Power of cortical field potentials from EEG [Time frame: Compared with and without stimulation at visit 7/8 to visit 24/25 (~end of week 2 and end of week 5)]
• Canadian Occupational Performance Measure (COPM)- Task Importance [Time frame: Compared with and without stimulation at visits 7/8, 16, and 24/25 (~end of week 2, beginning of week 4, and end of week 5)]
• Canadian Occupational Performance Measure (COPM)- Self-perception of performance [Time frame: Compared with and without stimulation at visits 7/8, 16, and 24/25 (~end of week 2, beginning of week 4, and end of week 5)]
• Canadian Occupational Performance Measure (COPM)- Self-perception of satisfaction [Time frame: Compared with and without stimulation at visits 7/8, 16, and 24/25 (~end of week 2, beginning of week 4, and end of week 5)]
• Patient Global Impression of Change [Time frame: Study visit 25 (~end of week 5)]

Eligibility criteria

Inclusion criteria

• Patients aged ≥18 years with incomplete traumatic SCI (American Spinal Injury Association (ASIA) B-D, levels between C4 to T1) incurred > 1 year before the start of the study
• At least 2/5 motor power in at least one upper extremity muscle group
• International Standards for Neurological Classification of Spinal Cord Injury Upper Extremity Motor Score (ISNCSCI-UEMS) ≤ 40/50
• Able to follow multistep commands
• Ability and willingness to provide informed consent
• English speaking

Exclusion criteria

• Cervical or thoracic stenosis that would preclude safe lead placement
• Any ongoing ventilator use (continuous or intermittent)
• Urinary tract infection or pneumonia requiring treatment (within past 3 months)
• Skin ulcers or other lesions
• History of posterior cervical fusion
• Autonomic dysreflexia requiring treatment (within past 3 months)
• Implanted brain stimulators
• Intracranial aneurysm clips
• Ferromagnetic metallic implants in the head (except for within mouth)
• Any active implanted device including intrathecal medication pumps or existing spinal cord stimulators (does not include non-active spinal instrumentation such as rods, screws, or interbody devices)
• Cochlear implants
• Cardiac pacemaker/defibrillator
• Any history of seizures
• Family history of idiopathic epilepsy in a first degree relative
• Bipolar disorder
• Any history of suicide attempt
• Active psychosis
• Intracranial lesion or increased intracranial pressure
• History of stroke or intracranial neurologic conditions with structural damage
• Medications that lower seizure threshold
• Substance use that lowers seizure threshold (heavy alcohol use)
• Moderate to severe heart disease
• Pregnancy or plans to become pregnant within the study period
• Any other medical or psychological condition that precludes involvement in the study as determined by a study physician

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 2 centers

• NewYork-Presbyterian Hospital / Columbia University Irving Medical Center (NYPH/CUIMC) — New York
• NewYork-Presbyterian Allen Hospital / Columbia University Irving Medical Center (NYPH/CUIM — New York

Identifiers

NCT: NCT06867809 · AAAV3409 · 5UE5NS070697-15

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗