Official Title: “Pilot Clinical Trial With Memantine for Cognitive Deficits in Patients With Multiple Sclerosis”

To assess the efficacy of Memantine in improving the cognitive impairment in patients with Multiple Sclerosis (MS)

Study Type: Interventional

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

Study Primary Completion Date: March 2008

Memantine is an NMDA receptor antagonist that improves cognitive and behavioural deficits in patients with Alzheimer disease, vascular dementia and mixed dementia. This study is focused in proving the efficacy of Memantine in ameliorating one of the most frequent symptoms of patients with MS which is attention and memory deficits. Memantine is a safe drug in patients with MS and it has been administered to MS patients with pendular nystagmus (Starck et al J Neurol 1997). The study will have the power to detect differences in such clinical question by studying 60 MS patients with cognitive impairment (n=60)) with a crossover design. Indeed, we plan to use a new and powerful surrogate marker such as attention evoked potentials developed in our center.

Finally, because there are evidences that Memantine might improve MS outcome by closing the Brain-Blood barrier (which is the best therapeutic target in this disease) (Paul et al J Pharmacol Exp Ther 2002), an exploratory study of its efficacy in preventing new MRI lesions might also be included in the design.

Aims: To assess the efficacy of Memantine in improving the cognitive impairment in patients with Multiple Sclerosis (MS) Primary end-point: to assess the efficacy of Memantine in improving memory deficit in MS patients using the SRT scale

Secondary end-points:

1. To assess the efficacy of Memantine in improving the performance in the individual neuropsychological tests for attention (PASAT3, SDMT, Stroop), executive (Raven, MATTIS) and memory (10/36, SRT), in the neuropsychological global scale BRB-N Z (Sepulcre et al, submitted) in quality of life (SF36), disability (EDSS, MSFC, MSSS) and fatigue (Krupp).

2. to assess the effect of Memantine in attention evoked potentials (EP)

3. to assess the effect of Memantine in clinical course (new relapses, relapse rate, patients free of relapses), disability (EDSS, MSFC, MSSS) and MRI parameters (active lesions: new T2 lesions, change in T2 lesion load, new gadolinium enhancing lesions and global and regional atrophy) in the response to Memantine. MRI study is optional.

4. to identify the predictors of good or bad response to Memantine therapy by using EP as surrogate markers.

Design: double blind, randomize and crossover clinical trial with Memantine compared with placebo in MS patients. Because Memantine have a hal-life of 2 to 4 days period, at the end of the 6 month, patients we will stay 3 weeks without any therapy (placebo or Memantine) in order to washout Memantine in the therapeutic group

Intervention(s) in this Clinical Trial

• Drug: Memantine
  • Memantine 30 mg/day (20-10-0)
• Drug: Placebo
  • Placebo pills

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: A
  • Memantine 30 mg/day
• Placebo Comparator: B
  • Placebo

Primary Measures

• to assess the efficacy of Memantine in improving memory deficit in MS patients using the SRT scale
  • Time Frame: 6 months
    Safety Issue?: No

Secondary Measures

• 1. tests for attention (PASAT3, SDMT, Stroop), executive (Raven, MATTIS) and memory (10/36, SRT), quality of life (SF36), and fatigue (Krupp). 2. attention evoked potentials 3. clinical course, disability (EDSS, MSFC, MSSS).
  • Time Frame: 6 months
    Safety Issue?: No

Inclusion Criteria:

• Patients with MS (McDonald 2002), both sex, age between 18 to 60 years old, all MS subtypes (RR, SP, PP, PR), stable.
• Patients with severe cognitive impairment defined as performing 1.5 SD below control group (matched by age and education) in 2 o more subtests based in our previous study (Sepulcre 2006):

Exclusion Criteria:

• Psychiatric diseases (Cummings) depression (Hamilton >8), drug or alcohol abuse, benzodiazepine therapy or other medical diseases.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Instituto Cientifico y Tecnologico de Navarra, Universidad de Navarra

Overall Clinical Trial Officials and Contacts

Pablo Villoslada, MD Principal Investigator Hospital of Navarra  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00638833

Study ID Number: 11495A

ClinicalTrials.gov Identifier: NCT00638833

Health Authority: Spain: Spanish Agency of Medicines

web page of the medical center of the University of Navarra