Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01874808 |
| Other study ID # |
GAITALS-C12-13 |
| Secondary ID |
2012-A01247-36 |
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 21, 2013 |
| Est. completion date |
December 21, 2015 |
Study information
| Verified date |
August 2021 |
| Source |
Institut National de la Santé Et de la Recherche Médicale, France |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
This research program will focus on gait initiation and postural control in Amyotrophic
Lateral Sclerosis (ALS) patients, by comparing patients with vs without postural instability
(but also in comparison to controls), by using a multidisciplinary approach which combines
neurophysiological and neuroimaging analyses.
After clinical evaluation, two groups of ALS patients, defined upon the feature of postural
instability, and one group of healthy subjects (n=25 for each group of patients and 20 for
healthy subjects) will be included in the study.
The neurophysiological evaluation will be performed through a gait initiation assessment,
which will alow us to collect biomechanical and electromyographical data, such as the braking
index.
The neuroradiological evaluation will include first an fMRI analysis, a study of specific
circuits in networks will be performed which will provide the first description of neural
network dynamics associated with the preparation and execution of movement in ALS patients.
The investigators major research hypothesis is:
- By comparing patients with vs without postural instability, but also in comparison to
controls, the investigators main research neurophysiological hypothesis is that patients
with postural instability will display an impaired braking.
- This impaired braking could be partly explained by a dysfunction and/or lesion of the
basal ganglia and brain stem structures, corresponding to the investigators main
neuroradiological hypothesis.
Description:
Compared to other movement disorders, such as Parkinson Disease (PD), the mechanisms of
movement impairment in Amyotrophic Lateral Sclerosis (ALS) have not been a focus of great
interest. It is at least partly related to the classical assumption that impairment of
movement in ALS simply reflects a dysfunction of the final motor pathways. However, the
concept that ALS purely involves upper and lower motor neuron has been definitively
challenged. Accumulating evidence for the concept that ALS is a multisystem degenerative
disease is supported by histological, neurophysiological and neuroimaging studies.
Clinically, lower limb stiffness is associated with extrapyramidal rigidity and postural
instability in 69% of ALS patients. These latter may also display abnormalities of movement
initiation impairing walking, such as gait initiation failure, usually reported in PD
patients. All these data support the hypothesis that some balance troubles in ALS patients
may result from an additional dysfunction and/or lesion of the basal ganglia circuitry and/or
of its output structures, such as the cortex or the midbrain.
In PD patients, which represent a model of basal ganglia system dysfunction, length and
velocity of the first step during gait initiation are known to be reduced and improved by
dopaminergic therapy whereas postural instability is less sensitive to the treatment
suggesting the involvement of other brain structures dysfunction and/or lesion. One way to
evaluate the postural control during the gait initiation process is to measure the vertical
velocity of the centre of gravity by using a force platform. In healthy adults, during the
single support phase, a forward fall of the centre of gravity occurs and is actively reversed
by the stance leg soleus muscle activation prior foot contact. In parkinsonian patients with
postural instability, this phenomenon, called active braking, is altered. It is assumed that
this postural instability results from additional lesions and/or dysfunction in the basal
ganglia output structures, especially in the midbrain, containing the pedunculopontine
nucleus and the mesencephalic locomotor region, two structures known to participate to the
control of locomotion and posture in animals.
This research program will focus on gait initiation and postural control in ALS patients, by
comparing patients with vs without postural instability (but also in comparison to controls),
by using a multidisciplinary approach which combines neurophysiological and neuroimaging
analyses.
After clinical evaluation, two groups of ALS patients, defined upon the feature of postural
instability, and one group of healthy subjects (n=25 for each group of patients and 20 for
healthy subjects) will be included in the study.
The neurophysiological evaluation will be performed through a gait initiation assessment,
which will alow us to collect biomechanical and electromyographical data, such as the braking
index.
The neuroradiological evaluation will include first an fMRI analysis. A study of specific
circuits in networks will be performed which will provide the first description of neural
network dynamics associated with the preparation and execution of movement in ALS patients.
If the investigators get a deeper understanding of the neural substrates underlying the
hypothetical impairment of gait initiation and postural control, the investigators will then
be able to develop adequate therapeutical strategies (pharmacological interventions, surgical
therapies, rehabilitation programs) aimed at improving movement preparation and gait
execution in ALS patients
