Therapy in Amyotrophic Lateral Sclerosis With Memantine at 20 mg BID (TAME)

Therapy in Amyotrophic Lateral Sclerosis With Memantine at 20 mg BID (TAME)

Quick Info:

Status:
Currently Recruiting
Estimated Enrollment:
90
Phase:
II
Treatment Type:
Orally available by tablet
Trial Type:
Double Blind Placebo Controlled
Sponsor:
University of Kansas Medical Center
Primary Investigator:
Contact Information:

Enrollment Criteria:

Forced Ventilation

Breathing Ability

Percent lung function (FVC) or (SVC)
>60%
Months/Onset

Months Since Onset

Number of months since first
symptoms of ALS
<36 months
BiPap Allowed

Non-Invasive Ventilation (NIV)

Can PALS use a BiPAP in the trial?
yes
DPS Allowed

Diaphragm Pacer (DPS)

Can PALS use a DPS in the trial?
maybe
Edaravone Usage

Edaravone Usage

Can a PALS use edaravone (Radicut/Radicava)
while enrolled in the trial?
Unknown

Update Notes:

1/4/2019Locations updated
11/7/2018Recruitment status updated
2/22/2018No significant updates
5/12/2017No significant updates
1/26/2017No significant updates
11/15/2016No significant updates
4/28/2016Locations and description updated.
8/7/2015Protocol updated.
6/1/2015No significant updates.
5/6/2014No significant updates.
4/23/2014New Trial added.

Locations:

Phoenix Neurological Associates, Phoenix, 85018
UC Irvine, Irvine, 92868
University of Kansas Medical Center, Kansas City, 66160
University of Washington, Seattle, 98195
University of Kansas School of Medicine - Wichita, Wichita, 67214
University of Florida, Jacksonville,, 32209
University of Kentucky, Lexington, 40536
University of Missouri, Columbia, 65201
Columbia University, New York, 10032
University of Texas Southwestern, Dallas, 75390
Nerve & Muscle Center of Texas, Houston, 77030

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):
News Articles and Summaries:
ALS Forum:
First Published on Clinicaltrials.gov: 4/15/2014
ClinicalTrials.gov ID: NCT02118727
Trial Protocol as Published on Clinicaltrials.gov:
ClinicalTrials.gov