Official Title: “Phase 2-3 - Memantine for Disability in Amyotrophic Lateral Sclerosis”

To study the effect of Memantine (uncompetitive, moderate affinity, NMDA receptor antagonist that binds to the NMDA receptor channel, and regulates the calcium influx into the neurons), a drug used to treat Alzheimer´s disease, on the progression of ALS. Memantine is added to riluzole (the single drug approved to treat ALS)

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: June 2008

Phase 2/3 trial in ALS patients Double-blinded, parallel, randomized (2 blocs, bulbar/spinal onset)

Memantine + riluzole x Placebo + Memantine

Inclusion criteria: - < 75 years at disease onset - < 3 years of disease progression - ALS-FRS > 24 - FVC > 60 - Probable or definite disease (revised El Escorial criteria) - No other medical condition - Normal blood tests - Regular medication on riluzole > 1 month - Nerve conduction studies ruling out conduction block - EMG with widespread loss of motor units (revised El Escorial criteria) - At least one hand with ADM strength > 2 on MRC scale

Duration - 2 years

Evaluation - every 3 months

Primary outcome - ALS-FRS Secondary -SF36, Hamilton depression scale, motor unit number estimation, neurophysiological index, strength (clinical evaluation); side-effects

Intention to treat analysis

60 patients

number estimated for 50% change in decline rate of ALS-FRS

Intervention(s) in this Clinical Trial

• Drug: Memantine
  • 10 mg bid
• Drug: memantine
  • 10 mg bid
• Drug: riluzole
  • riluzole 50 mg bid

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1 - active
  • memantine + riluzole
• Placebo Comparator: 2
  • riluzole + placebo

Primary Measures

• ALS-FRS
  • Time Frame: 12 months
    Safety Issue?: Yes

Secondary Measures

• QoL, depression scale, strength (clinical evaluation), forced vital capacity
  • Time Frame: 12 months
    Safety Issue?: Yes
• neurophysiology (motor unit counting, neurophysiological index)
  • Time Frame: 12 months
    Safety Issue?: No

Inclusion Criteria:

• Definite or probable disease - revise El Escorial criteria
• Normal blood tests
• Riluzole treatment during 1 month or more
• EMG in accordance with El Escorial criteria

Exclusion Criteria:

• Other diseases (such as PNP)
• Both ADM muscles < 3 on MRC scale
• Conduction block on nerve conduction tests
• Disease duration > 3 years
• ALS-FRS < 25
• Forced vital capacity - <60%

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 20 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Lisbon

Overall Clinical Trial Officials and Contacts

Mamede de Carvalho, MD Principal Investigator Department of Neurology- Hospital de Santa Maria  

Overall Contact: Mamede de Carvalho, MD + 351 21 7805219 mamedemg@mail.telepac.pt

Information obtained from ClinicalTrials.gov on January 08, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00353665

Study ID Number: 002-04

ClinicalTrials.gov Identifier: NCT00353665

Health Authority: Portugal: National Pharmacy and Medicines Institute