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Grants and Contracts Details
Description
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects 30,000
Americans each year. Of these 30,000 Americans, it has been suggested that up to 50% will
experience cognitive and behavioral changes in the form of frontotemporal dysfunction and up
to 40% will meet criteria for frontotemporal dementia (FTD). Riluzole the only FDA approved
agent for ALS extends a patient's lifespan by 2-3 months, and there are no proven therapies for
the cognitive changes associated with ALS. More effective therapy for this universally fatal
disease is needed. Results from an open label pilot trial of 20 patients treated with memantine
at 10 mg twice a day (BID) suggested that treatment with the combination of memantine and
riluzole slowed ALS disease progression. This trial also showed that levels of specific protein
biomarkers in the cerebrospinal fluid (CSF) at baseline correlated with the rate of disease
progression. A concurrent Phase 2 study found no effect with similar dosing; however, the study
was limited in terms of power. Comments on previous failed drug trials in ALS have raised the
concern that many ALS trials study a potential therapeutic agent at only a single dose and thus
may miss the potential efficacy of non FDA approved doses; therefore, this proposed study will
test a higher dose of memantine, 20 mg BlD, in a double blind, placebo controlled, randomized
trial of 90 patients with ALS to determine if a combination therapy of memantine with riluzole
can slow disease progression compared to treatment with riluzole alone. The primary outcome
measure will be the rate of disease progression as measured by the ALS Functional Rating
Scale-Revised (ALSFRS-R). ln addition the investigators will examine the cognitive deficits seen
in ALS patients measured by the ALS Cognitive Behavioral Screen (ALS-CBS) and the
Neuropsychiatric lnventory Questionnaire (NlP-Q). Finally, specific validated protein biomarkers
found in the CSF will be examined to determine if there is a correlation between the levels of
these biomarkers and the rate of disease progression. ln particular the investigators will
measure the ratio of phosphorylated heavy neurofilament to complement 3 (pNFH/C3) to see if
this ratio is predictive of disease progression and if the levels change during therapy with
memantine.
Status | Finished |
---|---|
Effective start/end date | 6/1/18 → 9/30/21 |
Funding
- University of Missouri
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Projects
- 1 Finished
-
Phase 2B Trial of Memantine for the Treatment of Amyotrophic Lateral Sclerosis
Kasarskis, E. (PI)
9/17/20 → 9/30/21
Project: Research project