Memantine for Disability in Amyotrophic Lateral Sclerosis (MEDALS)

Study Overview
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Brief Summary
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The purpose of this trial is 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 Amyotrophic Lateral Sclerosis (ALS). Memantine is added to riluzole (the single drug approved to treat ALS).

Detailed Description
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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

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

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: Memantine (Ebixa)
* Drug: riluzole
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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%

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 - active<br>memantine + riluzole | Drug: Memantine (Ebixa)<br>* 10 mg bid<br>* Other names: Ebixa;Drug: riluzole<br>* riluzole 50 mg bid<br>* Other names: rilutek;|
| Placebo Comparator: 2<br>riluzole + placebo | Drug: riluzole<br>* riluzole 50 mg bid<br>* Other names: rilutek;Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ALS-FRS |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| QoL, depression scale, strength (clinical evaluation), forced vital capacity |  | 12 months | 
| neurophysiology (motor unit counting, neurophysiological index) |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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amyotrophic lateral sclerosis, motor neuron disease, memantine, clinical trial