Efficacy of RIVAstigmine on Motor, Cognitive and Behavioural Impairment in Progressive Supranuclear Palsy
Status:
Recruiting
Trial end date:
2022-08-31
Target enrollment:
Participant gender:
Summary
Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease from the
parkinsonian syndrome group. It represents 5 to 10% of all parkinsonian syndromes and affects
3,000 to 10,000 persons in France. PSP is characterised by a doparesistant parkinsonism with
axial signs such as early gait instability and falls, oculomotor signs such as a vertical
gaze palsy, dysphagia and dysarthria, and both cognitive and behavioural disturbances. The
latter predominantly manifest as psycho-motor slowness, apathy and frontal executive
deficits. Swallowing impairments and falls may lead to life-threatening situations and death
occurs 6-9 years after disease onset.
Apart from L-dopa which may transiently and inconsistently improve motor symptoms no
effective symptomatic, disease-modifying or neuroprotective therapy is presently available to
reduce disability in any way. Therefore these patients often receive mostly non-medical care
such as physiotherapy and speech therapy.
In addition to dopaminergic degeneration there is evidence of cholinergic deficits in PSP
correlated with gait and balance impairments . This stands in contrast with the limited
number of studies of cholinergic augmentation strategies in PSP.
Trials of cholinesterase inhibitors in PSP have produced rather conflicting results:
donepezil improves cognition but deteriorates some motor functions whereas a case series of 5
PSP patients treated with rivastigmine found an improvement in several cognitive aspects and
no deterioration of motor functions .On the other hand in Parkinson's disease there is
convincing evidence of a positive effect of rivastigmine on cognition , apathy and falls
Investigators' hypothesis is that rivastigmine (an acetyl- and butyryl-cholinesterase
inhibitor) may reduce gait and postural impairment in PSP and may therefore limit the number
of falls and their consequences both in terms of injuries sustained (fractures etc...) and on
the patients' autonomy. In addition investigators hypothesise that rivastigmine may also
reduce the cognitive and behavioural impairment associated with PSP. Taken together these
improvements are likely to produce a significant effect on the patients' quality of life and
their caregiver burden.