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Quick Info
Status
Currently Recruiting
Estimated Enrollment
90
Phase
2
Treatment Type
Orally available by tablet
Trial Type
Double Blind Placebo Controlled
Primary Investigator
Richard D Barohn, MD- University of Kansas
Contact Information
Locations
United States, Arizona
Phoenix Neurological Associates, Phoenix, AZ, 85018, United States
United States, California
UC Irvine, Irvine, CA, 92868, United States
United States, Florida
University of Florida, Jacksonville,, FL, 32209, United States
United States, Kansas
University of Kansas Medical Center, Kansas City, KS, 66160, United States
University of Kansas School of Medicine - Wichita, Wichita, KS, 67214, United States
United States, Kentucky
University of Kentucky, Lexington, KY, 40536, United States
United States, Missouri
University of Missouri, Columbia, MO, 65201, United States
Coxhealth , Springfield, MO, 65802, United States
United States, New York
Columbia University, New York, NY, 10032, United States
United States, Pennsylvania
Penn State Hershey Medical Center, Hershey , PA, 17033, United States
United States, Texas
University of Texas Southwestern, Dallas, TX, 75390, United States
Nerve & Muscle Center of Texas, Houston, TX, 77030, United States
United States, Washington
University of Washington, Seattle, WA, 98195, United States
Enrollment Criteria
Breathing Ability
Percent lung function (FVC) or (SVC)
>60%
Months Since Onset
Number of months since first symptoms of ALS.
<36 months
Non-Invasive Ventilation (NIV)
Can PALS use a BiPAP in the trial?
yes
Diaphragm Pacer (DPS)
Can PALS use a DPS in the trial?
maybe
Edaravone Usage
Can a PALS use edaravone (Radicut/Radicava) while enrolled in the trial?
Unknown
Update Notes
Trial sites added, recruitment status updated
12/5/2019
updated recruitment status for several locations
11/7/2019
Locations updated
1/4/2019
Recruitment status updated
11/7/2018
No significant updates
2/22/2018
No significant updates
5/12/2017
No significant updates
1/26/2017
No significant updates
11/15/2016
Locations and description updated.
4/28/2016
Protocol updated.
8/7/2015
No significant updates.
6/1/2015
No significant updates.
5/6/2014
New Trial added.
4/23/2014

Other Information

Purpose
The purpose of this study is to determine if memantine at 20 mg BID when used in conjunction with riluzole, can slow down the disease progression of patients with ALS including potentially improving their neuropsychiatric changes, as well as determine if serum biomarkers can be used both as a diagnostic and a prognostic marker in patients with ALS.
Eligibility
Males and females ages 18-85 with clinically definite or probable ALS on stable dose of Rilutek 50 mg bid for at least 30 days prior to screening.
Details
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 desperately needed. Results from an open label pilot trial of 20 patients treated with memantine at 10 mg 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 CSF at baseline correlated with the rate of disease progression. A concurrent phase II study performed by Dr Carvalho, 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 BID, in a double blind, placebo controlled, randomized trial of 90 patients with ALS to determine if a therapy of memantine, especially in combination with riluzole, can slow disease progression compared to treatment with riluzole alone or no treatment. The primary outcome measure will be the rate of disease progression as measured by the ALS Functional Rating Scale- Revised (ALSFRS-R). In addition the investigators will examine the cognitive deficits seen in ALS patients measured by the ALS Cognitive Behavioral Screen (ALS-CBS) and the Neuropsychiatric Inventory Questionnaire (NPI-Q). Finally the investigators will examine specific validated protein serum biomarkers to determine if there is a correlation between the levels of these biomarkers and the rate of disease progression. In particular the investigators will measure the ratio of phosphorylated heavy neurofilament to Complement 3 to see if this ratio is predictive of disease progression and if the levels change during therapy with memantine. This project will offer unique insights into this untreatable disease. If this study confirms earlier results and suggests that memantine, when used in conjunction with riluzole, significantly slows down the progression of the disease, as well as ameliorates cognitive deficits in patients with fronto-temporal dysfunction, it will set the groundwork for conducting a larger phase III trial.
Collaborator(s)
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Trial Protocol as Published on Clinicaltrials.gov
NCT02118727 (First Published: 4/15/2014)