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Memantine Therapy in Amyotrophic Lateral Sclerosis (TAME)

This study has been completed.
Sponsor:
Collaborator:
Forest Laboratories
Information provided by:
Phoenix Neurological Associates, LTD
ClinicalTrials.gov Identifier:
NCT01020331
First received: November 20, 2009
Last updated: November 23, 2009
Last verified: November 2009

November 20, 2009
November 23, 2009
June 2005
July 2009   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01020331 on ClinicalTrials.gov Archive Site
Change in muscle strength as measured by quantitative dynamometry (baseline vs 18 months) [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Memantine Therapy in Amyotrophic Lateral Sclerosis
Phase IIA Open Label Trial of Memantine in Combination With Riluzole (Customary Care) for the Treatment of ALS

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Amyotrophic Lateral Sclerosis
Drug: Memantine
Experimental: ACTIVE
Intervention: Drug: Memantine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
20
October 2009
July 2009   (final data collection date for primary outcome measure)

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
Both
18 Years to 85 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01020331
Memantine in ALS
Yes
Todd Levine, MD, Phoenix Neurological Associates, LTD
Phoenix Neurological Associates, LTD
Forest Laboratories
Not Provided
Phoenix Neurological Associates, LTD
November 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP