Safety and Tolerability of Perampanel in Amyotrophic Lateral Sclerosis Patients
Status:
Terminated
Trial end date:
2021-07-01
Target enrollment:
Participant gender:
Summary
Amyotrophic lateral sclerosis (ALS), the most common motor neuron disease, is a fatal
progressive neurodegenerative disease affecting motor cortex, brainstem and spinal cord
leading to motor neuron death. It is a devastating disease of the anterior and lateral
corticospinal tracts with approximately 3 years mean duration from symptoms onset to death,
one-fifth survival at 5 years and only 10% may make it to 10 years.
Among the neuronal death pathways, excitotoxicity mechanism is considered to be the
foremost-involved mechanism. AMPA receptors are thought to be the prime mediator of the fast
excitation in spinal motor neurons, where they are expressed ubiquitously. AMPA receptor
antagonist was able to prevent this acute degeneration in previous animal studies.
The investigators aim to study the tolerability and safety of the novel AMPA antagonist,
perampanel, in patients diagnosed with ALS. Perampanel [2-(2-oxo-1-phenyl-5-
pyridin-2-yl-1,2-dihydropyridin-3-yl) benzonitrile] with its selective non-competitive AMPA
antagonism, was recently approved for epilepsy. Various long-term trials studying perampanel
in epilepsy showed favorable tolerability profile and most common side effects were mainly:
dizziness, headache and somnolence. All patients presenting to Neurology clinics at AUBMC
diagnosed with Amyotrophic Lateral Sclerosis, will be considered for the study. Investigators
will obtain informed consents from all patients who agree to be enrolled in this study in
accordance with institutional review board (IRB) requirements. Patients of both genders and
over 18 years old who meet the El Escorial criteria for possible, probable or definite ALS
and fit the inclusion criteria will be recruited. Subjects should not be started on riluzole
for the past 30 days or stable on a dose of riluzole for at least 30 days prior to the
screening process.
In titration phase, perampanel dose will be increase by 2mg/day increments every one week to
reach a maximum dose of 8 mg/day; reaching the maximum dose in four weeks. Treatment phase
will be followed by washout period during which, dose will be tapered by 2mg/day every 5 days
(over total of 15 days).