771213

research-article2018
NNRXXX10.1177/1545968318771213Neurorehabilitation and Neural RepairGalea et al

Original Research Article

Neurorehabilitation and

SCIPA Full-On: A Randomized Controlled

Neural Repair
1­–11
© The Author(s) 2018
Trial Comparing Intensive Whole-Body Reprints and permissions:
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Exercise and Upper Body Exercise After DOI: 10.1177/1545968318771213

https://doi.org/10.1177/1545968318771213
journals.sagepub.com/home/nnr

Spinal Cord Injury

Mary P. Galea, PhD1, Sarah A. Dunlop, PhD2, Timothy Geraghty, MBBS3,4,

Glen M. Davis, PhD5, Andrew Nunn, MBBS6, Liudmyla Olenko1,
and SCIPA Switch-On Trial Collaborators*

Abstract
Background. While upper body training has been effective for improving aerobic fitness and muscle strength after spinal
cord injury (SCI), activity-based therapies intended to activate the paralyzed extremities have been reported to promote
neurological improvement. Objective. To compare the effectiveness of intensive whole-body exercise compared with
upper body exercise for people with chronic SCI. Methods. A parallel-group randomized controlled trial was conducted.
Participants with a range of SCI levels and severity were randomized to either full-body exercise (FBE) or upper body
exercise (UBE) groups (3 sessions per week over 12 weeks). FBE participants underwent locomotor training, functional
electrical stimulation-assisted leg cycling, and trunk and lower extremity exercises, while UBE participants undertook
upper body strength and aerobic fitness training only. The primary outcome measure was the American Spinal Injury
Association (ASIA) motor score for upper and lower extremities. Adverse events were systematically recorded. Results. A
total of 116 participants were enrolled and included in the primary analysis. The adjusted mean between-group difference
was −0.04 (95% CI −1.12 to 1.04) for upper extremity motor scores, and 0.90 (95% CI −0.48 to 2.27) for lower extremity
motor scores. There were 15 serious adverse events in UBE and 16 in FBE, but only one of these was definitely related to
the experimental intervention (bilateral femoral condyle and tibial plateau subchondral fractures). No significant between-
group difference was found for adverse events, or functional or behavioral variables. Conclusions. Full-body training did not
lead to improved ASIA motor scores compared with upper body training in people with chronic SCI.

Keywords
spinal cord injury, randomized controlled trial, FES cycling, locomotor training, upper body training

Introduction
The prediction of neurological recovery after spinal cord
injury (SCI) has been based on physical examination of the
acute patient using the International Standards for the
Neurological Classification of Spinal Cord Injury
(ISNCSCI).1 The degree of spared volitional control is an
important predictor of functional outcomes, such as walk-
ing ability.2 Rehabilitation programs after SCI have tradi-
tionally focused on achieving optimal independence
expected for a specific injury level, given the identified
activity limitations and participation restrictions, and may
rely on compensatory strategies.3 While this approach may
result in improvements in independent function, it does not
promote recovery of motor control in the paralyzed limbs.
Loss of sensorimotor function after SCI induces muscu-
loskeletal and metabolic adaptations which are associated
1
The University of Melbourne, Parkville, Victoria, Australia
2
The University of Western Australia, Crawley, Western Australia,
Australia
3
The Hopkins Centre, Research for Rehabilitation and Resilience, Metro
South Health, and Griffith University, Logan Campus, Queensland, Australia
4
Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
5
The University of Sydney, Lidcombe, New South Wales, Australia
6
Austin Health, Heidelberg, Victoria, Australia
*Collaborators are listed in the Collaborators section at the end of this
article.
Supplementary material for this article is available on the
Neurorehabilitation & Neural Repair website at http://nnr.sagepub.com/
content/by/supplemental-data.
Corresponding Author:
Mary P. Galea, Department of Medicine (Royal Melbourne Hospital), The
University of Melbourne, Parkville, Victoria 3010 Australia.
Email: m.galea@unimelb.edu.au
2 Neurorehabilitation and Neural Repair 00(0)
with a higher risk of cardiovascular disease compared with
the general population.4 Regular physical activity can
improve fitness and psychosocial well-being in the SCI
population; however, a systematic review of combined
muscle strength and aerobic training (upper body training)
has reported that there is a limited number of low-quality
studies with inconsistent findings.5 Additionally, recent
research provides new understanding of the benefits of
exercise after SCI, including its positive impacts on the ner-
vous system.6
The concept of activity-based therapies arose from
research in animals and humans showing that recovery of
function could be enhanced through activity-dependent
plasticity driven by neuromuscular activation below the
level of injury.7 These therapies include locomotor training
and functional electrical stimulation (FES)–assisted exer-
cise. While most research attention has focused on the ben-
efits of these interventions for people with incomplete
SCI,8-10 those with complete lesions may also benefit, since
it is recognized that many are electrophysiologically incom-
plete (discomplete), that is, have subclinical evidence of
descending cortical influence below the level of injury.11 To
date, interventions that exercised the paralyzed limbs have
mostly been investigated as single entities using a range of
research designs, and with various endpoints. The most
recent systematic review of activity-based therapies for the
lower limbs included a meta-analysis showing that, com-
pared with no intervention or conventional physical inter-
ventions, activity-based therapy was not more effective for
improving independence, lower limb mobility, or quality of
life.12 The effects of locomotor training in people with
motor incomplete SCI (American Spinal Injury Association
Impairment Scale—AIS C and D) on balance and ambula-
tion have been investigated in a multisite observational
study,13 whereas a randomized controlled trial (RCT) inves-
tigated the effect on walking ability of treadmill versus
overground walking training.9 An RCT in people with
motor incomplete SCI10 and a nonrandomized, nonblinded
study14 have reported improvements in neurological recov-
ery (ASIA motor score) and walking performance after
combinations of activity-based interventions. There is a
need for high-quality evidence to address this question.
The primary objective of this project was to investigate
the effectiveness—on neurological recovery—of an inten-
sive “whole-body” exercise program compared with an
upper body only training program in people with complete
and incomplete SCI. The activity-based program included
locomotor training, FES-assisted leg cycling, and trunk and
lower extremity exercises. In the case of complete SCI,
locomotor training was used to explore the potential for
stimulating neurological improvement, rather than as a
means of attaining functional ambulation. Secondary objec-
tives were to examine functional and psychological changes
and quality of life.
Methods
Design
A multicenter, randomized controlled, assessor-blinded
trial was undertaken in community-dwelling participants
at 6 SCI units in Australia and New Zealand. The trial
was registered with the Australian and New Zealand
Clinical Trials Registry (ACTRN12610000498099) and
ClinicalTrials.gov (NCT01236976). The trial was man-
aged by a professional clinical trial management com-
pany (Neuroscience Trials Australia) and overseen by an
independent Data Safety Monitoring Board. Ethical
approval was obtained from the Human Research Ethics
Committees at each site.
Participants
Participants were included if they were more than 18 years
of age, had sustained a motor complete or incomplete trau-
matic SCI above the level of T12 at least 6 months prior to
consent, and had medical clearance to participate.
Participants were excluded if they had a pressure injury,
history of long bone fracture, or were postmenopausal. Full
inclusion and exclusion criteria are detailed in the pub-
lished protocol.15
Randomization
Participants were randomized to groups using a computer-
generated randomization schedule, stratified by site and
and injury status (AIS A/B or AIS C/D) using permuted
blocks of random sizes. Randomization occurred after
completion of baseline assessments and was controlled
independently by Neuroscience Trials Australia. Assessors
and statisticians performing the analyses were blinded to
group allocation.
Usual Care
Participants had previously completed their primary reha-
bilitation but were required to cease any other therapeutic
intervention (eg, physiotherapy, occupational therapy, FES,
or complementary therapies) during the 12-week interven-
tion period.
Full-Body Exercise Program
Participants in this group received a triad of interventions
comprising locomotor training, FES-assisted cycling, and
trunk and upper and lower extremity exercise. These inter-
ventions were provided at the participating spinal units 3
times per week over 12 weeks. Training in the delivery of
the interventions was provided to all staff prior to trial
commencement.
Galea et al 3
Locomotor training was deployed using a Therastride
system (Innoventor Inc, St Louis, MO). The intervention
was conducted in accordance with published protocols.16
Training sessions initially comprised a series of 1- to 2-min-
ute bouts of stepping training, interspersed with rests, for up
to 30 minutes of stepping. As the participants improved
their stepping ability, the duration of stepping intervals was
increased to maintain progressive overload in longer inter-
vals of up to 7 to 10 minutes and the amount of body weight
support was gradually reduced as the participants improved
their ability to bear weight on the lower limbs.
FES-assisted cycling was provided using a RT300 cycle
(Restorative Therapies, Baltimore, MD) according to pub-
lished protocols.15,17 Amplitude and pulse width were var-
ied according to individual tolerance and capability.
Participants exercised at the maximal power output possi-
ble, commencing with 10 minutes of training and gradually
building up to an exercise duration maximum of 60 min-
utes. Warm up and cool down comprised 3 minutes of pas-
sive cycling.
Trunk and upper and lower limb exercises comprised
assisted and/or resisted movements in different positions
(eg, lying or weightbearing positions) aimed at facilitat-
ing and strengthening voluntary muscle activity and
improving movement quality. Participants also undertook
practice of functional tasks, involving moving the upper
body over and outside the base of support, and exercises
in motor imagery.
If participants missed any treatments during the inter-
vention period, additional sessions were offered at another
time during the week or during an optional additional week
at the end of the intervention period.
Upper Body Exercise Program
Participants in this group received a circuit-based exer-
cise program for the upper body, incorporating resistance
and aerobic training (eg, chest press, boxing, resisted
exercises, biceps/triceps curls, arm cranking). The
10-point Borg Rating of Perceived Exertion was used to
describe aerobic exercise intensity, with participants
expected to exercise between levels 4 and 8 on this scale.
This program was provided 3 times weekly over 12 weeks
and supervised by a therapist and/or clinical exercise
instructor. Guidelines for the content, delivery and pro-
gression of exercises were outlined in a handbook to
ensure standardization across sites.
Follow-up
At the end of the intervention period, all participants were
free to continue with an exercise program if they wished.
All therapy received by participants during the follow-up
period was recorded in a patient diary.
Outcome Measures
All measurements were taken at baseline, 12 weeks (ie, at
the end of the intervention period), and 24 weeks after ran-
domization by therapists blinded to group allocation.
Although the original protocol included a 12-month fol-
low-up assessment, this assessment was removed half-
way through the trial to reduce participant burden and
encourage recruitment.
Primary Outcome.  The primary outcome was neurologi-
cal function at 12 weeks, measured by the ASIA motor
score.1
Secondary Outcomes. All secondary outcome measures are
described in detail in the published protocol.15 They included
•• ASIA motor score at 24 weeks and ASIA sensory
scores at 12 and 24 weeks1
•• Leg exercise capacity, a graded exercise test using
FES cycling
•• Anthropometric measurements: Lower limb girths,
waist circumference and skinfold thickness. Leg vol-
umes were calculated by measuring girths at 7 levels
along the leg and the height between these levels
according to the protocol of Heesterbeek et al.18
Using this method, the leg is divided into 6 imagi-
nary cones (3 in the upper leg and 3 in the lower leg)
and the volume calculated for each cone. The volume
of each cone is calculated using the formula:
 Cupper 
girth +
2
1  
Volume cone ( L) = ⋅ H ⋅  (Cupper girth ⋅ Clower girth ) + 
12π  2 
 Clower girth 
 
•• Spinal Cord Independence Measure (SCIM)
•• Measures of trunk function: Maximal balance range,
and the Spinal Cord Injury–Falls Concern Scale
(SCI-FCS).
•• Walking tests (for participants capable of walking):
6-Minute Walk Test (6MWT) and 10-Meter Walk
Test (10MWT).
•• Spasticity over the previous week was measured via
self-report using the Penn Spasm Frequency Score
(PSFS). Any change in the dosage of antispasticity
medication during the intervention period was also
monitored.
•• Pain was measured using the SCI version of the
Multidimensional Pain Inventory (SCI-MPI).
•• Psychological Measures included: Perceived Stress
Scale, Hospital Anxiety and Depression Scale
(HADS), Multidimensional Health Locus of Control,
Moorong Self-Efficacy Scale and Rosenberg Self-
Esteem Scale.
4 Neurorehabilitation and Neural Repair 00(0)
•• Quality of Life measures included the Assessment of
Quality of Life–8 (AQoL-8), the Health Utilities
Index Mark 3 (HUI3), and the WHO QoL-BREF.
Adverse Events. All adverse events (AEs) and serious
adverse events (SAEs), whether related or unrelated to
the interventions, were monitored and recorded. Clinical
investigators or site coordinators used clinical judgement
to determine severity, causality, and expectedness of all
adverse events.
Data Analyses
Sample Size Calculation.  We powered this study to detect a
between-group minimum worthwhile treatment effect on
the ASIA motor score at 12 weeks of 4.0 at the postinter-
vention time-point (SD 1) based on available published
data.14 A sample size of 188 participants (94 per group) was
estimated to provide 80% power to detect a significant
intervention effect (2-sided, P = .05) using an analysis of
covariance model that included baseline ASIA motor score
as a covariate, a correlation between baseline and post-
intervention ASIA motor score of at least 0.8, and an adjust-
ment to allow for a dropout rate of 20%.
Data Integrity and Management.  Data were stored electroni-
cally on a database with secured and restricted access and
an audit trail in line with ICH GCP (International Confer-
ence on Harmonisation of technical requirements for regis-
tration of pharmaceuticals for human use Good Clinical
Practice) guidelines.
Monitoring
The trial was overseen and monitored by a Program Manager
and Data Safety Monitoring Board. The Program Manager
ensured data quality and monitored compliance with the trial
protocol during visits to each site. Interim safety analyses
were planned to take place when 60 and 120 participants had
completed their postintervention assessment.
Statistical Analysis
All endpoints and analyses were prospectively catego-
rized as either primary or secondary. The primary and
secondary endpoints analyses were conducted according
to a predetermined analysis plan on an intention-to-treat
basis and using the full dataset comprising all randomized
participants. In addition, a per protocol analysis of the
primary outcome for participants who adhered to all
aspects of the protocol and received at least 80% of the
training sessions was undertaken. Differences in both pri-
mary and secondary endpoints between the two arms of
the study were tested independently at the .05 level of
significance, using a linear regression model with robust
sandwich estimator that also included the baseline value
of the given outcome in question as a covariate. No for-
mal adjustments were undertaken to constrain the overall
type I error associated with the secondary analyses, as
their purpose was to supplement evidence from the con-
firmatory primary analysis to help more fully characterize
the treatment effect. Results from the secondary analyses
were interpreted in this context.
The intention-to-treat strategy was based on an assump-
tion that data were missing at random. The sensitivity of
the results to plausible departures from the missing-at-
random assumption as part of the intention-to-treat analy-
sis were explored by using both a selection model
(modeling of the missing data mechanism) and a pattern
mixture model (modeling of the differences between miss-
ing and observed data). Assumptions about the missing
data were expressed via a parameter that measures the
degree of departure from the missing-at-random assump-
tion. The results were graphed over a range of assumptions
using the rctmiss suite of commands in Stata (version 13,
StataCorp, College Station, TX).
Results
Recruitment
A total of 748 potential participants with SCI were
screened for inclusion. Of these, 116 were eligible, agreed
to participate and were subsequently randomized to the
FBE or UBE groups. Figure 1 shows the reasons for exclu-
sion and the flow of participants through the trial. Despite
extensive screening through each spinal unit, recruitment
took longer than expected and because of the limited fund-
ing period, the trial was terminated after randomization of
116 participants. This protocol change was made prior to
data analysis.
Participants
Table 1 presents demographic data and baseline characteris-
tics for each group. The groups were similar with respect to
age, time since injury, and AIS classification.
Primary Outcome
No statistically significant between-group differences were
found for the primary outcome measure (Table 2). The
adjusted between-group difference for the upper extremity
motor score (UEMS) was −0.04 (95%CI −1.12 to 1.04) and
for the lower extremity motor score (LEMS) 0.90 (95% CI
−0.48 to 2.27). The results of the per protocol analysis were
similar (UEMS, difference = −0.002, 95% CI −1.11 to 1.1;
LEMS difference = 0.81, 95% CI −0.64 to 2.26).
Galea et al 5

Figure 1.  CONSORT (Consolidated Standards of Reporting Trials) flowchart for intention-to-treat analysis.

Fifteen participants recorded a change in their AIS classifi- Adverse Events

cation over the period of the trial (Table 3), though there
appeared to be no consistent pattern within or between groups.
Secondary Outcomes
There were no statistically significant between-group
differences for any of the secondary outcome measures
(Table 2, Supplementary Tables 1 and 2). There was neither
consistent trend toward improvement nor deterioration of
walking performance on the 10-m walk test or the 6-minute
walk test; the number of participants in each group who
could walk (FBE, n = 14; UBE, n = 10) was low. Both
groups showed a small reduction in waist circumference.
Thirty-one SAEs (16 FBE, 15 UBE) and 719 AEs (404
FBE, 309 UBE) were recorded over the 6-month trial
period. One SAE in FBE (bilateral medial femoral condyle
and tibial plateau subchondral insufficiency fractures) was
considered to be definitely related to the intervention; this
participant was withdrawn from the intervention and all
sites were notified. The Therapeutic Goods Administration
(TGA), Data Safety Monitoring Board and Human Research
Ethics Committees from all SCIPA sites provided additional
guidance for screening participants but permitted the study
to continue. No other changes were made to the study as a
result of this event. Another SAE in FBE (severe worsening
6 Neurorehabilitation and Neural Repair 00(0)

Table 1.  Demographics and Baseline Characteristics. from participant disclosure. In these cases, a different asses-
sor completed the assessments.
FBE (n = 60) UBE (n = 56)
Age, y, median (IQR) 40.1 (31.3, 49.9) 42.8 (29.6, 54.3)
Sex, n (%)
Discussion
 female 9 (15) 9 (16) The findings of our study do not support the hypothesis that
 male 51 (85) 47 (84) an intensive FBE program might lead to neurological recov-
Time since injury, y, 5.5 (1.9, 12.9) 3.9 (1.8, 10.3) ery, as assessed by the ASIA motor score. This was in con-
median (IQR) trast to the observations of Harness and colleagues,14 which
AIS classification, n (%)
is the only other study that sought to directly compare an
 A 29 (48) 28 (50)
upper body exercise program with a multimodal program
 B 9 (15) 8 (14)
that involved the trunk and lower limbs, and which also
 C 7 (12) 5 (9)
included participants with motor complete and incomplete
 D 15 (25) 15 (27)
Single neurological level, n
SCI. However, the study by Harness et al14 had a number of
 C2-C8 29 33 design flaws, including nonrandomization, nonblinding of
 T1-T6 18 13 assessors, and disparity between groups in time postinjury.
 T7-T12 13 10 Similarly, we found no significant between group differ-
Pain level, median (IQR) 0 (0, 3), n = 58 1 (0, 3), n = 54 ences in ASIA sensory scores in our study.
Other studies involving people with motor incomplete
Abbreviations: FBE, full-body exercise; UBE, upper body exercise; IQR, injuries have reported changes in neurological function as a
interquartile range; AIS, American Spinal Injuries Association Impairment
Scale.
result of a similar intensive FBE program. Jones et al,10 in a
randomized controlled trial with wait-list control, showed
significant improvements in the experimental group (total
back pain) was considered probably related to the interven- motor score and LEMS) compared with the control group.
tion and the participant was withdrawn. Other SAEs were No significant difference in LEMS was observed in an RCT
considered unrelated to the intervention and included severe comparing locomotor training with overground walking
autonomic dysreflexia (n = 3), chest infection (n = 3), and training in people with incomplete SCI, although partici-
bladder/catheter-related problems (n = 3). In UBE, 1 SAE pants were recruited a mean of 4.5 weeks postinjury.9 We
(feeling off balance, pain and loss of strength in upper did not require participants in our study to cease using pre-
limbs) was considered possibly related to the intervention. scribed oral baclofen for spasticity management. However,
All other SAEs in UBE were unrelated to the intervention: this agent, when used chronically, may lead to inhibition of
1 participant died of heart failure, but more than half the neuromuscular activity.19
SAEs in this group were related to bladder problems (n = 6). The mechanisms underlying changes in ASIA motor
Table 4 shows the most frequently recorded AEs considered score or function as a result of exercise have not yet been
definitely, probably, or possibly related to the intervention fully elucidated. These may include modulation of spinal
in both groups. neuronal excitability,20 reorganization of spinal neuronal
networks,21 and sprouting of uninjured corticospinal axons
Retention and Adherence to make contact with long propriospinal neurons which
increased their terminal arborization onto motor neurons.22
All participants had preplanned 36 training sessions over a In the case of humans with neurophysiologically discom-
period of 12 weeks. Eight participants withdrew consent plete SCI, exercise training may strengthen the connectivity
after randomization (6 UBE), 3 withdrew because of an SAE of extant descending pathways and lead to recovery of func-
or AE (2 FBE), 2 in FBE were withdrawn from the study for tion.23 Further electrophysiological studies are needed to
medical reasons. Thirteen participants in UBE received understand these processes in humans with SCI.
fewer than 80% (28/36) of the required interventions. In The proportion of participants in our study with AIS C
FBE, not all components of the triad of interventions were and D injuries was too low (30% of the sample) to discern
completed at each session; 15 participants received fewer any consistent difference in walking outcomes between
than 28 trunk exercise sessions, 18 received fewer than 28 groups. A systematic review24 of studies of locomotor inter-
FES-cycling bouts, and 21 participants received fewer than ventions (including body weight–supported treadmill train-
28 treadmill training sessions. There were multiple reasons ing and robotic-assisted training) included 8 RCTs of
for this, including illness, study or work commitments and variable quality examining a range of locomotor outcomes.
equipment failure. Overall, there is limited effectiveness of locomotor interven-
Blinding of assessors was well maintained, with asses- tions in people with incomplete SCI, although walking out-
sors being unblinded on only 8 occasions overall, mainly comes were superior in people with subacute injury. With 2
 Table 2.  Summary of Treatment Effects.

Baseline Postintervention (12 Weeks) Follow-up (6 Months) Between-Group Difference

ASIA Motor Score
(0-100 Points) FBE (n = 60) UBE (n = 56) FBE (n = 54) UBE (n = 49) FBE (n = 49) UBE (n = 40) 12 Weeks 6 Months
UEMS n = 53*  
  Mean (SD) 41.8 (12.0) 39.45 (11.7) 41.5 (12.1) 39.4 (11.9) 43 (26.5) 37. 5 (14.4) Difference: Difference: 1.65
−0.04
  Median (IQR) 50 (31.5, 50) 42.5 (29, 50) 50 (33, 50) 47 (27, 50) 49 (33, 50) 41 (12,33) P = .94, 95% CI P = .27, 95% CI
[−1.12, 1.04] [−1.3, 4.6]
LEMS n = 53  
  Mean (SD) 10.4 (14.9) 11.4 (17.9) 12.51 (17.0) 10.2 (17.2) 13.2 (17.5) 11.2 (17.8) Difference: 0.90 Difference: 1.19
  Median (IQR) 0 (0, 22) 0 (0, 28) 0 (0, 25) 0 (0, 10) 0 (0, 27) 0 (0, 25) P = .20, 95% CI P = .07, 95% CI
[−0.48, 2.27] [−0.09, 2.47]

Abbreviations: ASIA, American Spinal Injury Association; FBE, full-body exercise; UBE, upper-body exercise; UEMS, upper extremity motor score; LEMS, lower extremity motor score; IQR,
interquartile range.

7
8 Neurorehabilitation and Neural Repair 00(0)

Table 3.  Changes in American Spinal Injuries Association To our knowledge, this is the first study of exercise inter-
Impairment Scale (AIS) Classification.a ventions after spinal cord injury that has fully reported on
Time Since Injury (y) Baseline Postintervention 6 Months adverse events whether related to the trial interventions or
not. There was only 1 SAE that was definitely related to the
Full-body exercise study intervention (bilateral subchondral tibial plateau and
 1.7 D D C medial femoral condyle fractures) in a participant classified
 2.9 A A C as AIS A. A proximal tibial fracture in a participant classi-
 8.5 D C C fied as AIS C was reported following robotic treadmill
 12.4 C C D training.26 Clearly, it is important to be vigilant about the
 15.5 A B B
possibility of fracture given the higher risk in people with
 21.2 C B C
SCI. Dual energy X-ray absorptiometry (DEXA) is the
 32.0 C C D
most widely used method of assessing bone mineral content
Upper body exercise
and bone mineral density, but has limited utility for the pre-
 2.5 A C C
 2.6 A B B
diction of fracture threshold. Moreover, there are no bone
 4.5 B Unavailable C mineral density reference values for the sites at which insuf-
 4.7 B C B ficiency fractures typically occur in SCI. Peripheral quanti-
 4.8 A A C tative computed tomography (pQCT) is more precise in
 21.8 C C A people with SCI27 and can provide separate values for corti-
 22.8 C A B cal and trabecular compartments; this is important because
bone mass is lost through reduction of bone mineral density
a
Seven of 60 individuals (12%) in full-body exercise and 7 of 56 in the long bone metaphyses, whereas in the shaft, bone
individuals (12.5%) in upper body exercise changed AIS classification
over the trial duration. mass is lost through a reduction in thickness and an increase
in the porosity of the cortical wall.27 Guidelines for screen-
ing for fracture risk prior to a person with motor complete
exceptions,9,25 the total sample sizes have been low. Although SCI undertaking load-bearing exercise such as locomotor
the originally calculated sample size in our study was not training would be useful. However, since there was only
achieved, participant numbers were reasonable considering one instance of fractures related to the intervention in our
the relatively low incidence and prevalence of SCI in study, on balance the intervention can be considered safe
Australia and New Zealand. The length of our interventions under clinical trial conditions.
(3 times per week for 12 weeks) was consistent with that in As shown in Table 4 among the most common AEs con-
the majority of published trials. This dosage may be insuffi- sidered to be definitely related to the interventions were skin
cient. In an observational study of locomotor training13 par- abrasion/bruising, autonomic dysreflexia, and pain, well-
ticipants received a median of 47 training sessions (range recognized risks for exercise interventions. Skin abrasion or
20-251), with the number of intervention sessions deter- bruising was mostly caused by rubbing of straps or knocking
mined by participant progress. However, the feasibility of of limbs against apparatus. The incidence of this and auto-
regular attendance for intensive training needs to be exam- nomic dysreflexia was more common in FBE. Five instances
ined in light of the barriers to exercise participation in people of dizziness/nausea were reported as possibly related to the
with SCI, especially socioeconomic factors. A significant experimental intervention; this may be related to postural
proportion of participants in our study were unable or unwill- hypotension. Fifteen instances of headache in UBE partici-
ing to attend all the required sessions because of work or pants were considered possibly or probably related to the
study commitments, or ill health. intervention; these may be symptoms of autonomic dysfunc-
We observed changes in AIS classification in 14 partici- tion. Pain was commonly reported in both groups, and
pants (FBE n = 7; UBE n = 7; Table 3), with both improve- although the site was frequently not recorded, there were
ments and deterioration. Although spontaneous AIS instances of upper limb pain resulting from the use of gym
conversion has been reported within the first 12 months apparatus. Continual vigilance by treatment staff is therefore
postinjury, it is noteworthy that several participants in both required to minimize injury and compromise of health for
groups with AIS A classification converted to AIS B or C, participants in intensive exercise programs.
which can be interpreted as neurological improvement, Since intensive exercise programs can feasibly only be
even though they were between 2.5 and 32 years postinjury. provided for a limited period, mechanisms to facilitate
Of possible concern is that 2 participants with long-term ongoing participation in physical activity need to be consid-
(21.8 and 22.8 years) injuries in UBE converted from AIS C ered. There is increasing evidence that participation in exer-
to A or B, indicating deterioration of function; however, cise and sport promotes physical and psychological
conversely, 2 participants with long-term (21.2 and 32 well-being in people with spinal cord injury.28 Among the
years) injuries in FBE converted from AIS A to B or C. benefits of such exercise is a reduction in cardiovascular
Galea et al 9

Table 4.  The three most common types of adverse events reported during the study

Definitely related Probably related Possibly related

FBE n=85 n=53 n=56
Total N=194 Skin abrasion/bruising (n=25) Pain (n=17) Pain (n=20)
Autonomic dysreflexia (n=19) Skin abrasion/bruising (n=16) Dizziness/nausea (n=5)
Pain (n=17) Autonomic dysreflexia (n=7) Bladder/bowel problems (n=5)
UBE n=28 n=40 n=64
Total N=132 Pain (n=19) Pain (n=27) Pain (n=34)
Autonomic dysreflexia (n=4) Headache (n=3) Headache (n=12)
Skin abrasion, bruising (n=2) Autonomic dysreflexia (n=3) Skin abrasion/bruising (n=4)
Fatigue (n=4)

risk factors. In spinal cord–injured people who are seden- Conclusion

tary, the levels of visceral fat are in the “at-risk” category.29
Obesity significantly increases the compressive forces on
the ischial tuberosities in people with SCI, thus increasing
the likelihood of deep tissue injury.30 Therefore, a reduction
in waist circumference in participants in both exercise
groups suggests a beneficial reduction in comorbidity.
We did not observe changes in quality of life, or on psy-
chological measures. However, a small qualitative study
conducted at one of the trial sites in parallel with this study
highlighted the benefits associated with study participation,
which increased motivation and interest in continuation of
physical activity after the trial; these included access to an
appropriately equipped gym in a supportive environment
and being able to safely challenge one’s physical and psy-
chological boundaries.31 Many barriers exist to participa-
tion in leisure time physical activity by people with SCI,
including motivation, finances, and accessibility to special-
ized programs or equipment.32 Programs to overcome some
of these barriers are now being developed28 and are similar
to the exercise program delivered to UBE in this study.
Ultimately however, while exercising the paralyzed limbs
is a necessary condition for neural activation, exercise on its
own may be insufficient to effect neurological change, and the
addition of neuromodulation may be needed to do so. Recent
studies of spinal cord neuromodulation using epidural stimu-
lation in people with motor complete injury33 have demon-
strated latent voluntary control below the level of injury; these
individuals had received 80 locomotor training sessions prior
to electrode implantation. Repetitive training such as locomo-
tor training engages central pattern generators which are sen-
sitive to tactile and proprioceptive input from the lower limbs
and serve to control stepping.34 Raising the level of excitabil-
ity of the spinal cord circuitry using epidural stimulation facil-
itates activity-dependent reorganization of the spinal neuronal
network via the propriospinal network. The advent of transcu-
taneous spinal cord stimulators35 brings this technology closer
to wider clinical translation and underlies the importance of
further investigation of the delivery and dosage of exercise
and neural stimulation programs.
Our study is the first RCT comparing whole-body exercise
with an upper body exercise program in people with spinal
cord injury. We did not demonstrate greater neurological
improvements as assessed by ASIA motor scores after a
whole-body exercise program compared with an upper
body exercise program of 12 weeks duration. The heteroge-
neity of our sample, which included participants with a
range of injury levels and severity, may have contributed to
this result. On the whole, both experimental and control
interventions were safe. Exercise is important for physical
conditioning and well-being after spinal cord injury and has
positive effects on nervous system function. However, exer-
cise may need to be combined with neuromodulation to
achieve neurological recovery.
Collaborators
Melanie Hurley (The University of Melbourne, Parkville, Victoria,
3010, Australia) - Trial coordinator
Janette Alexander (Austin Health, Heidelberg, Victoria, Australia)
- Site coordinator
Sarah Fereday (Royal Rehab, Ryde, NSW) - Principal
investigator
Clare Goodman (Royal Rehab, Ryde, NSW) - Site coordinator
Julia Batty (Prince of Wales Hospital, Randwick,NSW) - Principal
investigator
Trent Li (Prince of Wales Hospital, Randwick, NSW) - Site
coordinator
Prof John Buchanan (Royal Perth Hospital, Perth, Western
Australia) - Principal investigator
Julie Bullick (Royal Perth Hospital, Perth, Western Australia) -
Site coordinator
A/Prof Ruth Marshall (Hampstead Rehabilitation Centre,
Lightsview, South Australia) - Principal investigator
A/Prof Jillian Clark (Hampstead Rehabilitation Centre,
Lightsview, South Australia) - Site coordinator
Dr Rick Acland (Burwood Spinal Unit, Christchurch, New
Zealand) - Principal investigator
Dr Jo Nunnerley (Burwood Academy of Independent Living,
Christchurch, New Zealand) - Site coordinator
10 Neurorehabilitation and Neural Repair 00(0)
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect
13. Harkema SJ, Schmidt-Read M, Lorenz DJ, Edgerton VR,
to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support
for the research, authorship, and/or publication of this article: The
study was funded by the Transport Accident Commission
(Victorian Neurotrauma Initiative), the Lifetime Care and Support
Authority NSW, the University of Melbourne and The University
of Western Australia.
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