Memantine Therapy for Multiple Sclerosis - Full Text View

Sponsors and Collaborators:	Instituto Cientifico y Tecnologico de Navarra, Universidad de Navarra H. Lundbeck A/S
Information provided by:	Instituto Cientifico y Tecnologico de Navarra, Universidad de Navarra
ClinicalTrials.gov Identifier:	NCT00638833

Purpose

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

Condition	Intervention	Phase
Multiple Sclerosis	Drug: Memantine Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Crossover Assignment, Efficacy Study
Official Title:	Pilot Clinical Trial With Memantine for Cognitive Deficits in Patients With Multiple Sclerosis

Resource links provided by NLM:

MedlinePlus related topics: Memory Multiple Sclerosis

Drug Information available for: Memantine Memantine hydrochloride

U.S. FDA Resources

Further study details as provided by Instituto Cientifico y Tecnologico de Navarra, Universidad de Navarra:

Primary Outcome Measures:

to assess the efficacy of Memantine in improving memory deficit in MS patients using the SRT scale [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome 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 ] [ Designated as safety issue: No ]

Enrollment:	20
Study Start Date:	September 2007
Estimated Study Completion Date:	March 2008
Estimated Primary Completion Date:	March 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Active Comparator Memantine 30 mg/day	Drug: Memantine Memantine 30 mg/day (20-10-0)
B: Placebo Comparator Placebo	Drug: Placebo Placebo pills

Detailed Description:

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:

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

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00638833

Locations

Spain, Navarra
Clinica Universitaria de Navarra
Pamplona, Navarra, Spain, 31008

Sponsors and Collaborators

Instituto Cientifico y Tecnologico de Navarra, Universidad de Navarra

H. Lundbeck A/S

Investigators

Principal Investigator:

Pablo Villoslada, MD

Hospital of Navarra

More Information

Additional Information:

web page of the medical center of the University of Navarra This link exits the ClinicalTrials.gov site

Publications:

Sepulcre J, Vanotti S, Hernández R, Sandoval G, Cáceres F, Garcea O, Villoslada P. Cognitive impairment in patients with multiple sclerosis using the Brief Repeatable Battery-Neuropsychology test. Mult Scler. 2006 Apr;12(2):187-95.

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Villoslada P, Arrondo G, Sepulcre J, Alegre M, Artieda J. Memantine induces reversible neurologic impairment in patients with MS. Neurology. 2009 May 12;72(19):1630-3. Epub 2008 Dec 17.

Responsible Party:	Insituto Cientifico Tecnico - Universidad de Navarra ( Guillermo Garcia del Barrio )
Study ID Numbers:	11495A
Study First Received:	March 12, 2008
Last Updated:	March 18, 2008
ClinicalTrials.gov Identifier:	NCT00638833 History of Changes
Health Authority:	Spain: Spanish Agency of Medicines

Keywords provided by Instituto Cientifico y Tecnologico de Navarra, Universidad de Navarra:

Multiple Sclerosis

Study placed in the following topic categories:

Excitatory Amino Acids
Neurotransmitter Agents
Dopamine
Autoimmune Diseases
Multiple Sclerosis
Demyelinating Diseases

Memantine
Demyelinating Autoimmune Diseases, CNS
Dopamine Agents
Sclerosis
Autoimmune Diseases of the Nervous System

Additional relevant MeSH terms:

Neurotransmitter Agents
Autoimmune Diseases
Demyelinating Diseases
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Anti-Dyskinesia Agents
Physiological Effects of Drugs
Nervous System Diseases
Antiparkinson Agents
Excitatory Amino Acid Agents
Sclerosis

Pharmacologic Actions
Multiple Sclerosis
Pathologic Processes
Therapeutic Uses
Demyelinating Autoimmune Diseases, CNS
Memantine
Dopamine Agents
Central Nervous System Agents
Autoimmune Diseases of the Nervous System
Excitatory Amino Acid Antagonists

ClinicalTrials.gov processed this record on September 10, 2009