The reporting of this study conforms to the CONSORT (Consolidated Standards of Reporting
Trials) Statement for non-pharmacologic trials
[
13]. The study was approved by the IRCCS Fondazione Don Gnocchi ethics committee.
Subjects
Persons with recent stroke, admitted for early rehabilitation to the inpatient Neurology
Unit of the IRCCS Fondazione Don Gnocchi in Florence, Italy, from April 2011 to February
2012, were screened for enrollment. Inclusion criteria were: (1) first ever ischemic
or hemorrhagic stroke, (2) age ≥18 years, (3) admission within 4 weeks from stroke
onset, (4) severe functional limitation in walking (score 0 or 1 in the Functional
Ambulation Classification, FAC)
[
14], (5) tolerance to the standing frame of at least 10 min (assessed two days after
admission), (6) stable clinical conditions, (7) adequate participation and cognitive
capacity, and (8) ability to provide informed consent.
Exclusion criteria were: (1) clinical contraindications to prolonged upright position
(e.g. postural hypotension), (2) previous stroke, (3) severe limitations of the range
of motion, particularly the lack of hip and knee extension, and ankle dorsiflexion,
(4) the presence of recent fractures of the pelvis or lower limb (if full weight-
bearing was not allowed) and (5) any other co-morbidity or disability that would preclude
participation in the training program. Eligible subjects signed an informed consent
conforming to the Helsinki Declaration, which contained detailed information on study
design and data management.
Study design and procedures
After inclusion and baseline assessment, participants were stratified according to
the FAC score (0 and 1). They were then randomly assigned to either adjunctive 20
or 40 min of SSP (experimental interventions), or standard (see below) CPT only (control).
The random sequence was generated by an investigator not involved in participants’
assessment (MDB) using a web-based application (
http://www.randomizer.org). Allocation assignment was kept concealed using serially numbered, opaque, sealed
envelopes.
Baseline and follow-up evaluations were performed by an independent physical therapist
(GD), blinded to group allocation and otherwise uninvolved in the study. Treatments
were administered by physical therapists five days a week for three weeks, in an inpatient
setting. Assessments were done at enrollment (T0), at the end of the 3-week treatment
(T1), and three months later (T2).
A formal sample size calculation was not performed because of lack of adequate preliminary
data on the expected effect size. In particular, the present RCT differed from previous
studies in the outcome measures chosen, in the overall duration of the treatment period
and in the double dosing (20 and 40 min/day) of the intervention.
Experimental treatment
Participants randomized to the 40-min daily SSP treatment received 2 20-min sessions
(morning and afternoon). The standing frame STANDY (Ormesa®,
www.ormesa.com) was utilized for the experiment. Equipped with heel rests, knee pads and back rest
(both adjustable in width, depth, and height) it allows a flexible and safe static
regimen.
Patients’ positioning on the standing and monitoring were conducted by the treating
physical therapists. Exercise duration was timed and inconveniences or discomforts
were recorded. The standing session was not performed, or could be interrupted, if
participants showed intolerance or hypotension.
Conventional physical therapy treatment
All participants underwent individual CPT sessions, which included 60 min of neuromuscular
and musculoskeletal interventions, and practice of functional activities
[
15]. Moreover, 20 min of passive cycling (upper- and/or lower- limbs), hydrokinetic and
occupational therapy were administered, as well as cognitive and speech therapy when
needed.
Data
Demographic and main clinical characteristics (stroke type, days from event, and affected
side) were recorded. Stroke severity was assessed with the National Institute of Health
Stroke Scale (NIHSS). The clinical history of participants was investigated for any
contraindications to upright position. Goniometric measurement of the range of movement
of the lower limbs was performed to exclude limitations that might affect the ability
to stand. Moreover, the ability to control the trunk in an upright position (sitting
and standing) was recorded. Tolerance to the standing frame was assessed by measuring
blood pressure, heart and respiratory rate first in the supine and seated positions,
and then after 5 min of standing. Signs and symptoms of hypotension were monitored.
As a safety measure, blood pressure and heart rate were recorded also during the interventions.
Primary outcome measures
The Fugl-Meyer Assessment of Motor Recovery after Stroke - motor domain (FM) scale,
the Functional Independence Measure (FIM), and the FAC were chosen as primary outcome
measures.
The FM, used in both clinical and research settings, is one of the most widely used
quantitative measures of motor impairment, with excellent intra- and inter- rater
reliability and construct validity, particularly of the motor domain, as shown by
numerous studies
[
16]. The motor domain includes items measuring movement, coordination, and reflex action
about upper- and lower- limb; motor score ranges from 0 (hemiplegia) to 100 points
(normal motor performance), divided into 66 points for the upper extremity and 34
points for the lower extremity. The FIM measures the level of disability and indicates
how much assistance is required to perform activities of daily living
[
17]. The FAC categorizes subjects according to basic motor skills necessary for functional
ambulation
[
14].
Secondary outcome measures
The Modified Ashworth scale (MAS), the Timed-Up-and-Go test (TUG) at three months
(T2), the drop in systolic blood pressure from supine to standing position, and the
ability to control the trunk while sitting or standing were taken as secondary outcome
measures.
The MAS
[
18] evaluates spasticity in patients with lesions of the central nervous system; knee
flexors and extensors, ankle dorsal and plantar flexors, and hip adductors of the
affected side were assessed. The TUG is a widely used mobility test, which requires
that a person rises from a chair, walks three meters, turns around, walks back to
the chair, and sits down again on the chair, while being timed
[
19].
Moreover, the Trunk Control Test (TCT)
[
20], which examines four simple aspects of trunk movement, was added to the protocol
after the study began, and was therefore administered in a subsample.
Statistical analysis
Data were analyzed by an independent investigator, blind to group allocation. Sample
characteristics were analyzed by descriptive statistics. Differences between groups
in baseline demographic and pre-training characteristics were examined using one-way
ANOVA for continuous and the chi-square test for ordinal and categorical variables
respectively, taking into account trends as appropriate. To perform the between-group
comparisons, a two-way ANOVA for repeated measures with group x time interaction was
used. The Kruskal-Wallis test was utilized to highlight the between-group differences
in the TUG test three months after the end of treatment.
Analyses were performed according to the intention- to- treat (ITT) and the per- protocol
(PP) principles
[
21]. For ITT analysis missing data were dealt with by using the last- observation- carried-
forward method
[
21]. The IBM SPSS Statistics for Windows, (version 20.0; IBM Corp, Armonk, NY) was utilized
for calculations. The significance level was set at a p value of <0 .05.="" p="">
Fig. 1. Study flow chart. Abbreviations: FAC = Functional Ambulation Categories; T0 = baseline;
T1 = end of treatment; T2 = follow-up (3 months)
Fig. 2. Mean outcome measures score as a function of time in the three groups. Error bars
represent the standard error. The TCT was administered in a subsample. Figure legend.
CTR = Control; 20’SSP = 20/min Supported Standing Practice; 40’SSP = 40/min Supported
Standing Practice. Abbreviations. As in Table 2
Fig. 3. T2 Timed Up and Go Test, between-groups comparison
