Memantine Therapy in Amyotrophic Lateral Sclerosis (TAME)
Primary Purpose
Amyotrophic Lateral Sclerosis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Memantine
Sponsored by
About this trial
This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring ALS
Eligibility Criteria
Inclusion Criteria
- Age 18-85
- Male or Female
- Clinically definite ALS by El Escorial criteria
- Elevated levels of Tau in CSF
Exclusion Criteria:
- Patients with FVC below 1.5 L or who require respiratory assistance
- History of liver disease
- Severe renal failure
- History of intolerance to Riluzole or Memantine
- Any other co morbid condition which would make completion of trial unlikely
- If female, pregnant or breast-feeding; or, if of childbearing age, an unwillingness to use birth control.
- Taking any trial medications. Non-trial medications are not cause for exclusion.
- Unwillingness to provide consent
Sites / Locations
- Phoenix Neurological Associates, LTD
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ACTIVE
Arm Description
Outcomes
Primary Outcome Measures
Standardized assessment of ALS disease progression through the ALS Functional Rating Scale (ALSFRS) and compare the levels of Tau at baseline, 6 and 12 months
Secondary Outcome Measures
Change in muscle strength as measured by quantitative dynamometry (baseline vs 18 months)
Full Information
NCT ID
NCT01020331
First Posted
November 20, 2009
Last Updated
November 23, 2009
Sponsor
Phoenix Neurological Associates, LTD
Collaborators
Forest Laboratories
1. Study Identification
Unique Protocol Identification Number
NCT01020331
Brief Title
Memantine Therapy in Amyotrophic Lateral Sclerosis
Acronym
TAME
Official Title
Phase IIA Open Label Trial of Memantine in Combination With Riluzole (Customary Care) for the Treatment of ALS
Study Type
Interventional
2. Study Status
Record Verification Date
November 2009
Overall Recruitment Status
Completed
Study Start Date
June 2005 (undefined)
Primary Completion Date
July 2009 (Actual)
Study Completion Date
October 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Phoenix Neurological Associates, LTD
Collaborators
Forest Laboratories
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Tau, a protein in the cerebrospinal fluid CSF is believed to be elevated in amyotrophic lateral sclerosis (ALS) patients. The investigators believe that Tau is truly a marker of increased neuronal death from any disease process. It is been shown that Memantine can inhibit and reverse the abnormal hyperphosphorylation of Tau and therefore the investigators are looking at the efficacy of Memantine at 10 mg twice a day (BID) to see if disease progression correlates with possible changes in Tau in ALS patients based on ALS Functional Rating Scale (ALSFRS) scores.
Detailed Description
We have been very interested in the role of developing a more active anti-excitotoxic cocktail for patients with ALS. As part of this interest we have been investigating potential markers for disease progression. One of our candidate markers has been the presence of elevated levels of TAU in the CSF of patients with ALS. While the presence of Tau was originally described as being used for adjunctive diagnostic testing in patients with Alzheimer's disease it has become clear that many neurodegenerative diseases possess elevated levels of Tau in the CSF. Therefore Tau is truly a marker of increased neuronal death from any disease process.
While levels of Tau have not been studied in depth in ALS, there was one report in 2003 which showed that 70% of ALS patients have elevated levels of Tau in their CSF (Sussmuth et al). We have also collected a series of 24 patients with clinically definite ALS and found that 22 of them had elevated levels of Tau at the time of diagnosis.
We have been intrigued by the findings that Memantine, an NMDA receptor antagonist, can inhibit and reverse the abnormal hyperphosphorylation of Tau which leads to sequestration of the normal Tau microtubules as well as microtubule associated protein 1 (MAP-1) and MAP-2. Further, Memantine has been shown to block the disassembly of microtubules which follows the hyperphosphorylation if Tau (Li et al., 2004).
We have submitted for presentation to the International Motor Neuron Disease meeting in 2005 the data on two anecdotal cases of patients with ALS. These two patients were diagnosed with ALS on clinical and electrophysiological data and they were found to have elevated levels of Tau in their CSF at the time of diagnosis. Both patients were treated with Riluzole, as standard therapy, and with Memantine 10 mg BID for 6 months. After 6 months their disease course was clearly very slow. A repeat analysis of their CSF showed that levels of Tau had returned to normal.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis
Keywords
ALS
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ACTIVE
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Memantine
Primary Outcome Measure Information:
Title
Standardized assessment of ALS disease progression through the ALS Functional Rating Scale (ALSFRS) and compare the levels of Tau at baseline, 6 and 12 months
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Change in muscle strength as measured by quantitative dynamometry (baseline vs 18 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Age 18-85
Male or Female
Clinically definite ALS by El Escorial criteria
Elevated levels of Tau in CSF
Exclusion Criteria:
Patients with FVC below 1.5 L or who require respiratory assistance
History of liver disease
Severe renal failure
History of intolerance to Riluzole or Memantine
Any other co morbid condition which would make completion of trial unlikely
If female, pregnant or breast-feeding; or, if of childbearing age, an unwillingness to use birth control.
Taking any trial medications. Non-trial medications are not cause for exclusion.
Unwillingness to provide consent
Facility Information:
Facility Name
Phoenix Neurological Associates, LTD
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85018
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Memantine Therapy in Amyotrophic Lateral Sclerosis
We'll reach out to this number within 24 hrs