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
  Purpose

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.


Condition Intervention Phase
Amyotrophic Lateral Sclerosis
Drug: Memantine
Phase 2

Phoenix Neurological Associates, LTD has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase IIA Open Label Trial of Memantine in Combination With Riluzole (Customary Care) for the Treatment of ALS

Resource links provided by NLM:


Further study details as provided by Phoenix Neurological Associates, LTD:

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 [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change in muscle strength as measured by quantitative dynamometry (baseline vs 18 months) [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: June 2005
Study Completion Date: October 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ACTIVE Drug: Memantine

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.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01020331

Locations
United States, Arizona
Phoenix Neurological Associates, LTD
Phoenix, Arizona, United States, 85018
Sponsors and Collaborators
Phoenix Neurological Associates, LTD
Forest Laboratories
  More Information

No publications provided

Responsible Party: Todd Levine, MD, Phoenix Neurological Associates, LTD
ClinicalTrials.gov Identifier: NCT01020331     History of Changes
Other Study ID Numbers: Memantine in ALS
Study First Received: November 20, 2009
Last Updated: November 23, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Phoenix Neurological Associates, LTD:
ALS

Additional relevant MeSH terms:
Amyotrophic Lateral Sclerosis
Sclerosis
Motor Neuron Disease
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
TDP-43 Proteinopathies
Neuromuscular Diseases
Proteostasis Deficiencies
Metabolic Diseases
Pathologic Processes
Memantine
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 16, 2014