Memantine Therapy in Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis Clinical Trial

— TAME  

Official title:

Phase IIA Open Label Trial of Memantine in Combination With Riluzole (Customary Care) for the Treatment of ALS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01020331
• Other study ID #: Memantine in ALS
• Status: Completed
• Phase: Phase 2
• First received: November 20, 2009
• Last updated: November 23, 2009
• Start date: June 2005
• Est. completion date: October 2009

Study information

• Verified date: November 2009
• Source: Phoenix Neurological Associates, LTD
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: October 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria

1. Age 18-85

2. Male or Female

3. Clinically definite ALS by El Escorial criteria

4. Elevated levels of Tau in CSF

Exclusion Criteria:

1. Patients with FVC below 1.5 L or who require respiratory assistance

2. History of liver disease

3. Severe renal failure

4. History of intolerance to Riluzole or Memantine

5. Any other co morbid condition which would make completion of trial unlikely

6. If female, pregnant or breast-feeding; or, if of childbearing age, an unwillingness to use birth control.

7. Taking any trial medications. Non-trial medications are not cause for exclusion.

8. Unwillingness to provide consent

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• Memantine

Locations

Country	Name	City	State
United States	Phoenix Neurological Associates, LTD	Phoenix	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Phoenix Neurological Associates, LTD	Forest Laboratories

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		18 months	Yes
Secondary	Change in muscle strength as measured by quantitative dynamometry (baseline vs 18 months)			No