Powered Exoskeletons in Persons With SCI

Background Veterans with spinal cord injury (SCI) have many adverse secondary medical and
quality of life (QOL) changes as a result of immobilization. Veterans with SCI who have
completed rehabilitation after injury and are unable to ambulate receive a wheelchair as
standard of care (SOC) for mobility. Powered exoskeletons are a technology that has recently
become available as an alternate form of mobility by providing an external framework for
support and computer controlled motorized hip and knee joints to assist with overground
ambulation.

Research Questions (Objectives) Will Veterans with chronic SCI of six months duration, who
are medically stable and who use a wheelchair as SOC plus an exoskeletal-assisted walking
(EAW) device in their home and community environments have clinically meaningful net
improvements in mental health, bladder, bowel, and pain patient-reported outcomes compared
with those who use only the SOC? Additionally, will the use of an EAW device for four months
in the homes and/or communities of the participants result in a reduction of total body fat
mass? Study Design A two-group (Intervention and Control), randomized, clinical trial will be
performed with a one-year feasibility component. The Intervention group will receive SOC plus
EAW. The Control group will receive SOC only. The study will require seven years in total to
complete and includes fifteen VA SCI Services as study sites. A feasibility phase will be
employed using a staggered start by initially starting six sites, four sites starting one
year later, and 5 other sites starting two years later. These initial six sites will be used
to assess the start-up activities [hiring, training, equipment procurement, Central
Institutional Review Board (CIRB) paperwork, etc.], the rate of recruitment, and any other
issues that may be of value for the successful completion of the study. Lessons learned will
be implemented for the remaining sites.

Relevance to VA In pilot studies conducted at the James J. Peters VA Medical Center, Bronx,
NY, improvements in mental-emotional health, physical health and body composition were
demonstrated by providing the participants the ability to walk for 4 to 6 hours per week over
the course of three to five months. As of July 2014, a Class 2 designation was established by
the Food and Drug Administration (FDA) for "powered exoskeletons". To date, one device
(ReWalk ) has received FDA Class 2 approval for institutional and home use and is currently
available by prescription. The Department of Veterans Affairs (DVA) is the largest single
provider to persons with SCI in the USA, caring for about 26,000 of the 42,000 estimated
Veterans with SCI. The VA presently lacks the infrastructure to support Veterans with SCI to
train to use this device in order to make this technology available for the home/community
use. A controlled research study would be anticipated to be the optimal manner to demonstrate
the efficacy, amount of use and safety of a powered exoskeleton in the home and community
environments; findings would be immediately transferable to clinical care.

Number of Research Participants (Sample Size) One hundred-sixty participants (80/group) will
be randomized. Each of the 15 study sites will be expected to pre-screen 100 potential
participants, screen 60 participants, to reach the target of 160 randomized over 15 sites.

Participating Sites Fifteen SCI Services will be selected on the basis of potential
recruitment numbers (N=13,606 total Veterans with SCI in the sites' catchment areas and
N=7,022 followed annually at these sites) and geographic location, to permit an even
distribution across the country. The fifteen sites include: Boston, Richmond, St. Louis,
Tampa, Milwaukee, Minneapolis, Dallas, Houston, Palo Alto, Long Beach, Augusta, San Antonio,
Bronx, Cleveland, and Albuquerque. Of these fifteen sites, five are VA Cooperative Studies
Program (CSP) Network of Dedicated Enrollment Sites (NODES).

Duration of Participant Intake (Study Duration) The CS #2003 study duration is projected to
be a total of seven years: The initial six sites will have a start-up year, followed by
participant enrollment/data collection during years 1-4, and continued data
collection/closeout during year 5, for a total of six years. The next four sites will begin
the start-up year one year after the first six sites and follow the same enrollment, data
collection and closeout schedule over the next five years. The next five sites will begin
start-up one year after the four sites and follow the same enrollment, data collection and
closeout schedule. All fifteen sites will be closed out after six years, and there is an
additional year for the Coordinating Center and Chairperson's Office to complete data
analysis and manuscript writing, thus the study total time is seven years. Participants in
both groups will be asked to commit 33 weeks to this study. Participants in the Control arm
will be offered an additional 8 weeks to receive EAW training in the medical centers, without
outcome data being collected.

Treatment (follow-up) The intervention being tested is four months of home and/or community
use of a powered exoskeleton.

Definition of Participant Samples (Study Population) One-hundred sixty male or female
Veterans or military members with chronic SCI, six months duration, 18 years of age,
functional use of their hands, medically stable, and wheelchair users for indoor and outdoor
mobility, will be eligible for screening. All potential participants will be Veterans or
military members with SCI. Study participants will generally be outpatients with the
exception of those inpatients who meet the eligibility criteria, and who are approved by the
Site Investigator (e.g., some inpatients may have been admitted for a wheelchair fitting or
another non-medical reason). Non-veterans with SCI will not be eligible.

Treatment Arms All participants will receive four months of treatment, randomized into two
arms: SOC plus EAW or SOC only.

Endpoints Primary outcome one will be the Mental Component Summary of the Veterans Rand-36
(MCS/VR-36). Primary outcome two will be the sum T-score of the SCI-QOL bladder management
difficulties, bowel management difficulties and pain interference item banks. The major
secondary outcome will be total body fat mass. The two primary and the major secondary
outcomes will be analyzed as the proportion of participants in each group who achieved a
clinically meaningful change in score. The endpoint will be success or failure for these
outcomes.

Inclusion Criteria:

1. Veterans or active duty military personnel who are at least 18 years of age;

2. Traumatic or non-traumatic SCI 6 months duration of SCI;

3. Wheelchair-user for indoor and outdoor mobility;

4. Anthropometric compatibility with the device:

1. Weight <220 lb. (100 kg),

2. Thigh length between 14 and 19 in (36 and 48 cm),

3. Shank length between 17 and 22 in (43 and 55 cm);

5. Able to hold the crutches in hands without modifications;

6. Able to have a companion who can attend approximately one-third of the training
sessions who will assist them at home and in the community; and

7. Able to provide informed consent.

Exclusion Criteria:

1. Diagnosis of neurological injury other than SCI;

2. Progressive condition that would be expected to result in changing neurological
status;

3. Severe concurrent medical disease, illness or condition judged to be contraindicated
by the Site Physician;

4. Unhealed or unstable traumatic or high impact lower extremity fracture (definition
below) of any duration that is in the clinical judgement of the study physician to be
exclusionary for standing and walking;

5. Knee BMD < 0.60 gm/cm2;

6. Total hip BMD T-scores < -3.5;

7. Fragility, minimal trauma or low impact fracture of the lower extremity since spinal
cord injury (definition below);

8. Untreatable severe spasticity judged to be contraindicated by the Site Physician;

9. Flexion contracture > 15� at the hip and/or > 10� at the knee;

10. Limitations in ankle range of motion that cannot be adapted with an orthotic device
(plantar flexion > 00);

11. Untreated or uncontrolled hypertension (systolic blood pressure >140 mmHg; diastolic
blood pressure >90 mmHg);

12. Unresolved orthostatic hypotension (systolic blood pressure <90 mmHg; diastolic blood
pressure <60 mmHg) as judged to be contraindicated by the Site Physician;

13. Current pressure ulcer of the arms, trunk, pelvic area, or lower extremities;

14. Psychopathology documentation in the medical record or history that may conflict with
study objectives; and/or

15. Pregnancy or women who plan to become pregnant during the study period.