The INSPIRE Study: InVivo Study of Probable Benefit of the Neuro-Spinal Scaffold(TM) for Safety and Neurologic Recovery in Subjects With Complete Thoracic AIS A Spinal Cord Injury
This is an HDE probable benefit, open-label, non-randomized, single-arm, multicenter, study
to evaluate the safety and probable benefit of the poly((lactic-co-glycolic
acid)-co-poly-(L-lysine)) Scaffold ("Scaffold") in subjects with complete T2-T12/L1 thoracic
AIS A traumatic spinal cord injury.
Subjects who have experienced a recent (must receive Scaffold within 96 hours from injury)
spinal cord injury (AIS A) from T2 to T12/L1 (neurological spinal cord level) will be
screened for participation. After informed consent is obtained, neurological status will be
assessed according to the International Standards for Neurological Classifications of SCI
(ISNCSCI) as developed by ASIA. The 5-grade ASIA Impairment Scale will be used to determine
the completeness of a subject's injury. The ISNCSCI examination includes sensory and motor
function assessments. A rectal examination will be used to assess deep anal pressure
sensation and voluntary anal contraction to determine the completeness of the injury. Any
variables that may affect the ability to obtain a reliable ISNCSCI exam should be eliminated
(e.g., temporarily eliminating medication that would interfere with a valid ISNCSCI exam for
ventilated subjects). Furthermore, magnetic resonance imaging (MRI) studies without contrast
will be performed to measure and characterize the contusion and its location. The contusion
dimensions (length and anteroposterior diameter) will be estimated. The MRI will also be used
to assess the presence or absence of a cavity, parenchymal sparing, atrophic changes of the
cord, and areas of edema and hemorrhage. Other baseline assessments at screening will include
subject demographics, general medical/medication history, physical examination, neurological
exam, resting vital signs, Vital Capacity (VC) for subjects who are not ventilator dependent,
and baseline clinical laboratory tests. Body mass index (BMI) at screening will be calculated
based on actual, self-reported or family-reported weight and height.
For subjects ages 16 and 17, baseline skeletal maturity will be assessed using an accepted
measure (e.g. bone age as determined by hand and wrist x-ray or Risser stage as determined by
iliac crest x-ray) prior to hospital discharge, but assessment is not required prior to open
spine surgery/Scaffold implant. X-rays obtained during the preoperative period may be used
for this assessment.
If clinical assessments are conducted during post-injury care and before informed consent is
obtained, they may be used for the study once informed consent is obtained.
Within approximately 8 hours prior to open spine surgery, the AIS classification of the
subject will be confirmed to ensure only subjects with a reliable AIS A classification will
be implanted with the Scaffold. The Scaffold will be implanted at the time of open spine
surgery and not during a second or separate surgery, and ideally within 24 hours from the
time of injury but no longer than 96 hours from the time of injury.
After completion of the spine surgery, the Investigator will ensure the subject continues to
meet eligibility criteria.
For subjects with a T2 or T3 neurological level of injury, bilateral intraoperative median
and ulnar nerve somatosensory evoked potential (SSEP) monitoring will be performed as an
added safety precaution for the investigational procedure from durotomy through Scaffold
placement and dural closure. The objective of this monitoring is to identify potential loss
of neurologic function of the hand at the C8 and T1 neurologic levels. The median nerve
signals can be used as a control for the C8 and T1 levels as the median nerve also includes
contribution from C7. An adequate baseline should be obtained per institutional protocol to
ensure interpretable recordings from both median and ulnar SSEPs prior to beginning the
investigational procedure (i.e. prior to the durotomy). Should the SSEP recordings indicate
potential loss of function, appropriate steps should be taken per institutional guidelines
such as adjustment of anesthesia, operating procedure, etc. The Investigator should determine
whether the Scaffold can be placed safely if this deterioration occurs prior to Scaffold
placement. The Investigator may also utilize additional modes of intraoperative
neuromonitoring such as motor evoked potentials (MEPs), if the risk of upper extremity
movement is outweighed by the potential benefit. If the surgical procedure includes anterior
cord manipulation, stronger consideration should be given to use of MEPs of the abductor
pollicis brevis (C8, T1).
Changes in ventilator parameters due to worsening of pulmonary function will be documented
during the investigational portion of the open spine surgery (durotomy, myelotomy, Scaffold
implant, dural closure). If changes in ventilator parameters are necessitated by a worsening
of pulmonary function, the Investigator will document the ventilator setting changes and
assess if the worsening is due to the Scaffold implant procedure.
Upon visualization of the dura, an intraoperative ultrasound will be performed to evaluate
and confirm the contusion size, presence or absence of a cavity, and location of the
contusion, as initially assessed by the preoperative MRI. Based upon the contusion cavity
size, the Investigator will select and prepare an appropriately sized Scaffold. The
Investigator will then perform a durotomy, arachnoid/pial resection, and after the epicenter
of the contusion cavity has been identified/reached (e.g., by myelotomy), further irrigate
the contusion with isotonic saline for the purposes of debridement as necessary to remove
additional areas of hemorrhage and necrotic tissue within the cavity. During gentle
irrigation, Investigator will capture a sample of the spontaneous exudate if present and
submit to pathology for routine examination/testing, for example Hematoxylin and Eosin (H&E)
staining for histology. Next, the Scaffold will be placed into the epicenter of the
intra-spinal post-irrigation contusion cavity.
A second intraoperative ultrasound, with photograph, should be performed to confirm placement
of the Scaffold in the spinal cord. The dura will be closed in standard surgical fashion. If
there is significant spinal cord edema or swelling such that a standard primary dural closure
would compress spinal cord tissue, a duraplasty can be considered. The surgical wound will
then be closed and dressed according to standard clinical practice.
Following surgery, vital signs will be monitored and qualified medical personnel will perform
neurological examinations in a manner consistent with standard post-anesthesia care. Subjects
will be cared for in the hospital and after discharge following the standard medical care
practice for SCI patients.
The cylindrical-shaped Scaffold is a bioresorbable material, and based upon pre-clinical
testing, is expected to be cleared from the site of implant within four to eight weeks.
Therefore, the post-Scaffold implantation Follow-up study visits will be determined based on
the date/time the Scaffold implantation procedure was finished and will be at 24 hours, 48
hours, 72 hours, 1 week, at hospital discharge, 1 month, 2 months, 3 months, and 6 months.
The Long-Term follow-up visits will be in clinic at 12 months and 24 months, and annually by
phone for years 3 through 10.
Post-Scaffold implantation Follow-up assessments will consist of ISNCSCI, neurological
examinations (including hip abduction/adduction and great toe flexion/extension at Discharge
through 6 Month Primary Endpoint Follow-up Visit), Spinal Cord Independence Measure (SCIM
III), Ferrans and Powers Quality of Life Index - Spinal Cord Injury (QLI-SCI III), Beck
Depression Inventory-II (BDI-II), bowel and bladder function, routine laboratory tests, Vital
Capacity (VC) for subjects who are not ventilator dependent, and resting vital signs. In
addition, an MRI without contrast will be performed at the 72 Hour, 3 Month and 6 Month
Primary Endpoint Follow-up Visits, and a physical exam will be performed at the Discharge
Visit and the 6 Month Primary Endpoint Follow-up Visit. Safety event monitoring including
procedure and Scaffold related complications will occur at all Follow-up Visits and will
include adverse device effects (ADEs), unanticipated adverse device effects (UADEs), and all
serious safety events (SAEs/SADEs). Subjects will participate in comprehensive rehabilitative
programs for spinal cord surgery patients and a Rehabilitation Therapy Log will be completed.
Long-Term Follow-up assessments will be conducted in clinic at 12 months and 24 months
post-Scaffold implantation, and annually for years 3 - 10. In-clinic Long-Term Follow-up
Visits will consist of ISNCSCI, neurological examinations including hip abduction/adduction
and great toe flexion/extension, MRI without contrast, routine laboratory tests, resting
vital signs and a physical exam. At the 12 Month Long-Term Follow-up Visit only, SCIM III,
QLI-SCI III, BDI-II, and bowel and bladder function will be assessed. The Rehabilitation
Therapy Log will be completed through the 12 month Long-Term Follow-up Visit. Safety event
monitoring including procedure and Scaffold related complications will occur at the 12 Month
and 24 Month Long-Term Follow-up visits and will include adverse device effects (ADEs),
unanticipated adverse device effects (UADEs), and all serious safety events (SAEs/SADEs). An
annual telephone Long-Term Follow-up Visit will be conducted for years 3 - 10 and will
collect general health information. If at any time during the Follow-up or Long-Term
Follow-up periods, the subject reports a neurologic deterioration consisting of loss of bowel
or bladder function or complete loss of motor function at any joint that had at least 2+
movement at the prior examination, the subject will be asked to return to the clinic for a
Active, not recruiting | Spinal Cord Injury | Multisite