Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02356536 |
| Other study ID # |
2013000952 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 1
|
| First received |
January 28, 2015 |
| Last updated |
August 10, 2017 |
| Start date |
October 2013 |
| Est. completion date |
December 2015 |
Study information
| Verified date |
August 2017 |
| Source |
The University of Queensland |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The CuePeD trial is an intervention trial measuring the effectiveness of a novel treatment
for Freezing of Gait (FOG) in Parkinson's disease (PD). The primary intervention is the use
of a wearable cueing device (WCD), which detects and responds to FOG and extinguishes on the
resumption of normal walking. It is designed for use in PD patients with FOG, in their home
environment where FOG is most severe. Kinematic data will be logged by a memory card in the
belt worn device recording FOG, and falls. The device will be used on 3 different settings in
a gait laboratory environment, and then for 2 weeks in the patient's own home using the same
3 settings. A battery of psychometric instruments will be administered before and after the
trial
Description:
The CuePeD trial primarily involves the use of a WCD ( pictured on website
www.brightdevices.com.au). This is a belt worn device, with a co-location of motion sensor
input and cueing output. The input is mediated by miniaturized accelerometers and gyroscopes
and utilizes software algorithms which have been developed to detect FOG. The cueing output
is mediated by a laser light which shines on the floor in front of the user as a continuous
visual signal. The cue is produced because of the device's ability to recognize FOG in the
user. The laser is produced for a predetermined period of time or until normal gait is
recommenced, at which time it extinguishes until the next freezing episode.
This study plans to examine the effectiveness of the WCD for the problem of FOG in PD 'in
vivo', that is, in a community setting.
FOG has been defined narrowly as 'the sudden inability to initiate or sustain locomotion'. It
includes 'start', 'turn' and 'destination' hesitation. A broader definition accepted at the
2010 workshop of clinicians and scientists interested in FOG was " brief, episodic absence or
marked reduction of forward progression of the feet despite the intention to walk" . It
generally occurs several years after the onset of PD and has been recognized as a significant
source of morbidity in PD patients. Cueing represents one of the more promising treatments,
but the demonstration of in vivo effectiveness of this intervention to date, are modest.
Falls, while often multifactorial in a general population, in PD are often attributable to
FOG.
Unfortunately, current treatments for FOG are largely ineffective, and the evidence for their
use limited.
Interventions for FOG are usually pharmacological and involve manipulation of laevodopa (LD)
doses, or more recently, the addition of stimulants. Other centrally acting medications have
been described anecdotally as beneficial, but have not been systematically studied.
Possibly as a consequence of the decrease in postoperative laevodopa (LD) dose in chronic
users, or the under recognized significance of the subthalamic nucleus ( the most common
stimulation target) in gait regulation, the rise of Deep Brain Stimulation as a treatment for
PD may contribute to the problem.
The first study employing a wearable device to detect FOG was described by Bachlin in 2010,
but involved a 3 component device (an ankle worn motion sensor, belt worn processing unit and
earpiece for cueing output) and a pulsed auditory cue (a 1 Hz clicking sound).
One of the recurring difficulties for gait scientists is the inability to elicit FOG in
freezers' in vitro' in the laboratory. This is due to the artificial clinical environment
giving rise to a 'best performance' or 'paradoxical kinesia'.
Non-laboratory, 'in vivo' measures have been limited to user rated questionnaires at the end
of a trial period of in home use.
This freeze detecting, cue producing device offers an elegant solution for the amelioration
of FOG and possibly falls in a PD population in their day to day life. In addition, it offers
a novel opportunity for the objective measurement of kinematic data to assess the efficacy of
the device in individual subjects.
Whilst cueing has been recognized as a treatment for FOG for more than 25 years, most of this
work has occurred in gait laboratories. It is well known that FOG is induced in many subjects
with initiation of gait, turns and 'dual tasking'. This commonly occurs in the domestic
environment, where there are small spaces doorways, hallways etc.
Most 'in vitro' work has taken place with a fixed, pulsed cue, usually auditory, but
including visual and somatosensory/vibration pulses. Unfortunately, the landmark 2006 RESCUE
trial of Neiubauer demonstrated an improvement in gait that was not sustained once the cueing
device was removed. That is, the problem of FOG is not readily rehabilitated with cueing, and
benefits of cueing training quickly extinguish once the treatment finishes.
The neurobiology of why FOG occurs in this setting, while beyond the scope of this
description, is beginning to be understood, and is worthy of brief commentary to better
understand the WCD's mechanism of action. Several lines of evidence, including functional
imaging studies point to a failure of reconciliation of motor, cognitive and emotional
circuits in FOG prone patients. Mental tasks (such as counting backwards), additional motor
tasks (such as carrying a glass of water), as well as a feeling of severe anxiety itself can
all induce FOG. The presence of a doorway or kitchen bench, which requires contemplation,
similarly represents a dual tasking challenge which can induce FOG. Being optimally
emotionally aroused in a laboratory setting can assist overcoming the propensity to freeze.
The proposed research will be a case series analysis of 30 PD patients with clinically
significant FOG; recruited from local movement disorder neurologists. There will be no
blinding. There will be an ABA design with subjects acting as their own controls - the device
on continually, on during FOG episodes or off at different time periods. There will be
randomization of the 3 device settings for different time periods.
Each trial will take 2 weeks, with an initial gait laboratory assessment. During this
assessment signature freezing episodes will be captured, videoed, for each patient, and
correlated with kinematic readings. identification of FOG episodes and Inter-rater
reliability data will be obtained during these assessments. Patients will become familiar
with the use of the device for later use at home. 3 tasks will be undertaken by each patient
on each device setting - ie 9 tasks in total - these include: a timed up and go, 2 minute
walk and a specifically designed obstacle course. A battery of psychometric instruments will
be completed.
This assessment will then be followed by a 2 week home trial. 3 device settings will be
employed in both environments - 1. the device 'off' and simply measuring FOG using its
software algorithms, 2.the device "on" whereby FOG episodes trigger the laser cue, and 3. the
device on 'continually' whereby, a continuous visual cue is emitted from the device,
independent of FOG episodes .
The device will be on settings 1,2 and 3 for 3,7 and 4 days respectively, with randomisation
of the order of settings 2 and 3.
During the 2 week home trial, Kinematic data to capture FOG duration will be logged on the
device during the same time period each day with the device on different settings. Fall data
will collected from 6am to 10pm.
Crucially, FOG episodes on all 3 settings of the device will be recorded. The primary outcome
measure will be the total seconds of FOG when the device is simply recording compared with
the total FOG seconds when a FOG dependent ( or continuous FOG independent) cue is provided
by the device.
At the end of the 7 days on setting 2 (FOG dependent cue), instrument ratings will be
completed for a second time, and returned with the device for collation of the data.
Whilst cueing has been recognized as a treatment for FOG for more than 25years, most of this
work has occurred in gait laboratories. It is well known that FOG is induced in many subjects
with initiation of gait, turns and 'dual tasking'. This commonly occurs in the domestic
environment, where there are small spaces doorways, hallways etc.
One hypothesis regarding the limited efficacy conferred by current devices used for FOG, is
that pulsed, fixed auditory stimuli represent a cognitive burden and may actually induce FOG
once the initial freeze is overcome. The work of Wolpert would suggest that a pulsed auditory
cue extending beyond the freezing episode would at best be 'gated' out by the subject, and
essentially ignored. Bachlin's subjects complained that the auditory cue was annoying.
A fixed visual cue which extinguishes after the freeze is broken appeals as a powerful
antidote to this paradox of focusing the patient's attention at the point of freezing, but
not adding to their cognitive burden once the freeze is broken. This was recognized with the
first descriptions of cueing for FOG with an inverted walking cane. It is a powerful example
of the curiosity of paradoxical kinesia well known to the disorder, and not easily forgotten
by clinicians who have been witness to it. Until the recent development of increasingly
miniaturized, sophisticated accelerometers and gyroscopes, there was no mechanism to
replicate the effect of an upturned cane held by a walking companion.
It is now known that there is an increasing loss of automaticity in FOG patients, and an
increase in cortical connectivity with deep brain structures - that is, there seems to be a
'cortical takeover' of gait in these patients. It seems likely that a cue may more readily
enable a re-accessing of 'vestigial' gait motor programs in those patients that it helps.
The 2 null hypotheses of the research project will be: (1)That the wearable, freeze detecting
cueing device has no measurable effect on total freeze duration, total number of freezing
episodes , or total number of falls over the same three 1 hour intervals measured on separate
days in subjects with Parkinson's disease; and:(2)That there is no difference in user rated
instrument measures of Quality of Life, Freezing of Gait, Falls, Anxiety and Depression
before and after 2 weeks of treatment a wearable, freeze detecting cueing device in patients
with Parkinson's disease.
The proposed research will be a case series analysis of 30 PD patients with clinically
significant FOG; recruited from local movement disorder neurologists. There will be no
blinding. In both arms of the trial, there will be an ABA design with subjects acting as
their own controls - the device on and off at different time periods.
The assessments will include:
1. Freezing of Gait Questionnaire(FOGQ); Falls Efficacy Scale (FES); Parkinson's Disease
Questionnaire 39; Geriatric Anxiety Inventory (GAI), Geriatric depression scale (GDS);
Spielberger Trait Anxiety Inventory (STAI); Mini mental state examination MMSE and MOCA
.
2. 2minute walk test; Timed 'up and go' test; Dual tasking Timed up and go test;
standardized 20 metre obstacle course that includes a doorway, corridor, 180 and 360
degree turns.
Patients will then be asked to take the WCD home for 14 days with clear guidelines for its
use. The battery of questionnaires to be completed at the end of the 14 days, along with a
self addressed postal pack for the return of the device will accompany the patient.
