Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT04703556 |
| Other study ID # |
DBSgait2020 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
October 4, 2021 |
| Est. completion date |
July 6, 2023 |
Study information
| Verified date |
September 2023 |
| Source |
Centre Hospitalier Universitaire Vaudois |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
For decades, deep brain stimulation (DBS) therapies have been employed very successfully to
alleviate segmental motor symptoms (tremor, brady-kinesia or rigidity) in patients with
Parkinson's disease (PD). Unfortunately these therapies often fail to alleviate, or can even
aggravate, axial deficits such gait and balance disorders. This is presumably due to the
divergence in the dynamics of the circuits that control leg function, which are not well
addressed with commonly employed stimulation protocols.
To date, patients still endure life-long debilitating gait difficulties that severely affect
their everyday mobility, independence and quality of life.
In recent years, a handful of studies have proposed new paradigms, for instance using
different stimulation parameters that are thought to be better suited for targeting the
circuits that control lower limb function. Although promising, the resulting observations
have been far from conclusive. As a result, the relevant approaches for therapeutic
intervention remain unclear, and the underlying mechanisms largely unknown.
Advances on the use of implantable neuromodulation devices and of tech-nologies for
monitoring whole-body movement currently allow to study locomotor deficits in ecological
environments, enabling the recording and modulation of motor and neural signals while
patients perform activities of daily living, chronically, wirelessly and in real time.
Description:
This project seeks to leverage the latest technological innovations for monitoring and
modulating motor and neural states chronically, in order to comprehensively characterize gait
deficits in PD, and to clarify the improvements ushered in by varying DBS parameters.
The resulting observations will establish a rigorous understanding that will open new avenues
for the design of evidence-based, clinically-relevant DBS strategies for locomotor deficits.
Advances on the use of neural implants for electrical neuromodulation of deep brain
structures are opening the unique opportunity to probing the function of dysfunctional
circuits in patients suffering from a variety of neurological disorders.
To date, acute experiments using deep brain stimulation (DBS) implants, either in
intra-operative setups or shortly after surgery during so-called "externalization" phases,
have widened our understan-ding of the neural signatures that underlie various motor and
non-motor symptoms, and helped optimi-ze therapeutical parameters to better address such
impairments.
For instance, DBS therapies in Parkinson's disease (PD) have been refined over the past
decades based on experiments that synergistically (i) explored and uncovered readouts of
movement perfor-mance in response to changing stimulation parameters, (ii) identified the
underlying neural biomar-kers from recordings of local field potentials, and even (iii)
tested closed-loop strategies able to adapt in real-time to ongoing patient-specific
requirements.
These advances have mostly been applied to (and been successful for) improving motor signs of
the upper-limb such as tremor, bradykinesia or rigidity, which exhibit fast dynamical
responses to changes in neuromodulation (in the range of minutes), and which can be studied
in the context of simple motor tasks using tethered technologies while patients are safely
sitting or lying. These conditions have made it possible to tweak, tune and optimize
parameters based on simple easily measurable readouts of motor dysfunction, and to record
neural signals with minimal movement-related artefacts in the meantime.
Unfortunately, these straightforward experimental conditions do not apply to the study of
axial motor signs, such as locomotion:
- First, gait deficits are multi-faceted and high dimensional: Impairments are not merely
restricted to leg movements, but also critically affect lower- and upper-limb
coordination, trunk and pelvis oscillations, posture and balance. Their characterization
thus requires of multi-modal sensing technologies and analytical methods able to capture
all these aspects concurrently.
- Second, the emergence of key deficits (e.g. freezing of gait) necessitates of
behavioural tasks that are more physically demanding and potentially risky, often
involving multiple repetitions of back-and-forth stepping over longer distances or in
environments that resemble everyday life activities. Patients thus need to be in a
stable medical condition, and technologies must allow recordings of motor and neural
states to be performed wirelessly.
- Finally, the modulation of neural circuits controlling gait have considerably slower
dynamics in response to changes in DBS (up to several hours10) than those controlling
upper limb function, hence imposing that monitoring and tuning protocols are stretched
in time to appropriately capture such changes.
These requirements critically put forward the need to study and devise novel therapies for
gait deficits in the chronic state, using multi-modal technologies that can concurrently
record neural and motor states remotely, in real-time and for long periods of time.
This project seeks to leverage the latest technological innovations for monitoring and
modulating motor and neural states chronically, in order to comprehensively characterize gait
deficits in PD while patients execute a range of activities of daily living, and to clarify
the improvements brought in by varying DBS parameters.
In past years, a handful of studies have proposed new stimulation paradigms aimed to better
target the neural circuits that control lower limb function during gait11. For instance
strategies sought to combine varying DBS frequencies, or to target additional anatomical
targets. They all highlighted promising, yet far-from-conclusive results. To date, the
relevant approaches for therapeutic intervention remain unclear, and the underlying
mechanisms largely unknown. Patients still endure life-long, debilitating gait difficulties
that severely affect their everyday mobility and independence: they often feel insecure about
leaving their homes due to the high risk of fall-related injuries, require personal
assistance, and in general see their quality of life significantly diminished.
