Does Memantine Improve Verbal Memory Task Performance in Subjects With Partial Epilepsy and Memory Dysfunction?
This study is currently recruiting participants.
Verified January 2013 by American Academy of Neurology
Sponsor:
American Academy of Neurology
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Beth Leeman, M.D., Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01054599
First received: December 1, 2009
Last updated: January 4, 2013
Last verified: January 2013
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Purpose
Many patients with epilepsy have memory deficits in the setting of otherwise normal intelligence. Unfortunately, the treatment options for memory dysfunction in patients with epilepsy are limited. The investigators are conducting a study to evaluate the effects of memantine for the treatment of verbal memory dysfunction in subjects with localization-related seizures. The study involves randomization to memantine therapy or placebo, with cognitive testing and EEG pre- and post-treatment, as well as after an open-label memantine treatment phase.
The primary aim of this study is to evaluate the efficacy of memantine for the treatment of verbal memory dysfunction in subjects with left temporal lobe epilepsy. The investigators expect that verbal memory task performance will improve in those taking memantine, but not in those taking a placebo.
The investigators propose that the expected benefit of memantine is specific to verbal memory in subjects with left temporal lobe seizures, rather than representing an overall improvement in cognitive function. The investigators expect no improvement on other cognitive tasks in either the memantine or placebo groups.
The investigators will evaluate whether subjects with left temporal lobe epilepsy and memory difficulties have self-reported improvement in memory while taking memantine. The investigators expect improvement of self-rated memory function on the Quality of Life in Epilepsy Patient Inventory (QOLIE-89) in the memantine group, but no change on this scale in the placebo group.
| Condition | Intervention |
|---|---|
|
Epilepsy |
Drug: Memantine Other: Sugar Pill |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | Does Memantine Improve Verbal Memory Task Performance in Subjects With Localization-related Epilepsy and Memory Dysfunction? A Randomized, Double-Blind, Placebo-Controlled Trial |
Resource links provided by NLM:
Genetics Home Reference related topics:
autosomal dominant partial epilepsy with auditory features
pyridoxal 5'-phosphate-dependent epilepsy
U.S. FDA Resources
Further study details as provided by American Academy of Neurology:
Primary Outcome Measures:
- The change scores from pre- and post-treatment neuropsychological test evaluations will be compared between the placebo and memantine treatment groups. If the distributions are normal, we will perform a two-sample t-test. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- To test the hypothesis that improvement will be selective for verbal memory, change scores on the non-verbal tasks will be compared between the placebo and memantine treatment groups. If the distributions are normal, we will conduct a two-sample t-test. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To test the hypothesis that treatment with memantine will result in subjective improvement of memory function, the change scores from the QOLIE-89 will be evaluated. If the distributions are normal, we will proceed with a two-sample t-test [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- A secondary analysis will examine the possible sustained benefit of continued memantine use. [ Time Frame: 2 years ] [ Designated as safety issue: No ]The prediction is that subjects taking placebo will demonstrate improvement in the SRT-CLTR and 7-24 Spatial Memory Test scores between the second (post-placebo) and third (post-memantine) testing sessions. The expectation is that subjects randomized to memantine will demonstrate no change in memory test scores between the second (post-memantine) and third (post-memantine) testing sessions, reflecting sustained improvement from baseline. If the distributions are normal, we will conduct paired t-tests. If the distributions appear non-normal, we will use Wilcoxon signed rank tests.
| Estimated Enrollment: | 96 |
| Study Start Date: | January 2009 |
| Estimated Study Completion Date: | December 2013 |
| Estimated Primary Completion Date: | December 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Memantine
Subjects will randomly assigned to take either a placebo or memantine for 13 weeks. The assignment will be double-blind, neither the study members nor the subject will know if he/she is taking memantine or a placebo.
|
Drug: Memantine
All subjects in the treatment group will be placed on memantine. The dosage of memantine will begin at 5mg once per day (qday), and increase by 5mg every week. The titration will continue over a period of 3 weeks until a goal of 10mg bid is reached. The dosing will increase slowly, to minimize the risk of side effects. The subject will then remain on memantine at 10mg bid for 10 weeks, until the conclusion of the first phase of the study. At the conclusion of the first 13 weeks, subjects will discontinue the treatment (memantine or placebo) and enter the open label phase.
Other Name: Namenda
Drug: Memantine
Open label: When the blinded phase is complete (Weeks 1-13), all subjects will receive open-label treatment with memantine (Weeks 14-26). The dosage of memantine will begin at 5mg once per day (qday), and increase by 5mg every week. The titration will continue over a period of 3 weeks until a goal of 10mg bid is reached. The dosing will increase slowly, to minimize the risk of side effects. The subject will then remain on memantine at 10mg bid for 10 weeks, until the conclusion of the study. At the conclusion of the study, subjects will discontinue the treatment.
Other Name: Namenda
|
|
Placebo Comparator: Sugar Pill
Subjects will be randomly assigned to take either memantine or a placebo. The study is double-blind, and neither the study members nor the subject will know if he/she is taking memantine or a placebo.
|
Other: Sugar Pill
In the control arm of the study, subjects will take one placebo sugar pill per day for one week, then increase to one tablet twice per day for the following 12 weeks. At the end of this phase of the study, subjects will enter the open-label phase (unblinded treatment with memantine).
Other Name: Placebo
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 18-65 years of age
- Normal IQ as estimated by the Wechsler Test of Adult Reading (WTAR)
- Able to give consent
- Able to live independently and complete activities of daily living
- Stable frequency of seizures. There is no minimum/maximum criteria for the frequency of partial seizures. Those with infrequent secondary generalized seizures may participate, with infrequent seizures defined as two or fewer per year.
- The subject's treating physician does not believe a change in anticonvulsant regimen to be warranted. The anticonvulsant drugs must remain unchanged during the 26 week trial.
- Partial-onset seizures. Seizure type will be determined by clinical history, MRI, SPECT and/or PET imaging, and interictal and/or ictal EEG.
- Either symptomatic or idiopathic seizures.
Exclusion Criteria:
- Non-epileptic seizures
- Prior surgical resection for treatment of seizures
- Progressive neurologic illness (i.e. tumor evident on MRI)
- Current alcohol or drug abuse, as this may affect memory by other mechanisms. This information may be obtained by self-report, from the referring physician or by medical record.
- Diagnosis of Alzheimer's disease, nutritional deficiency, infection or metabolic/electrolyte disorder causing memory loss.
- Non-native English speaking and/or multilingual.
- Seizure(s) must not have occurred within 3 days of testing.
- Subjects who are pregnant will not be eligible to take part in the study, as memantine is classified as a Pregnancy Category B drug and may pose risk to the fetus.
- Women who are breastfeeding may not participate in this study.
- Those with renal tubular acidosis or infections of the urinary tract will not be eligible for participation, as memantine is renally cleared and conditions that alkalinize the urine may reduce clearance of the drug.
- Subjects with severe renal impairment, defined as a creatinine clearance of ≤29 mL/min, will be excluded as such patients may not tolerate the proposed dosing schedule.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01054599
Contacts
| Contact: Beth A Leeman, M.D. | 404-778-3181 | baleeman@partners.org |
| Contact: Samantha R Donovan, B.S. | 617-643-4617 | sdonovan@mclean.harvard.edu |
Locations
| United States, Georgia | |
| Emory University | Recruiting |
| Atlanta, Georgia, United States, 30322 | |
| Contact: Beth A Leeman, MD 404-778-3181 baleeman@partners.org | |
| Principal Investigator: Beth A Leeman, MD | |
| United States, Massachusetts | |
| Massachusetts General Hospital | Recruiting |
| Boston, Massachusetts, United States, 02114 | |
| Principal Investigator: Lauren Moo, M.D. | |
| Sub-Investigator: Beth A Leeman, M.D. | |
| Newton-Wellesley Hospital | Recruiting |
| Newton, Massachusetts, United States, 02462 | |
| Contact: Eduardo Garcia, MD 617-928-1500 eduardo.garciamd@gmail.com | |
| Principal Investigator: Eduardo Garcia, MD | |
Sponsors and Collaborators
American Academy of Neurology
Forest Laboratories
Investigators
| Principal Investigator: | Lauren Moo, M.D. | Massachusetts General Hospital |
More Information
Additional Information:
Publications:
| Responsible Party: | Beth Leeman, M.D., Assistant in Neuroscience, Massachusetts General Hospital |
| ClinicalTrials.gov Identifier: | NCT01054599 History of Changes |
| Other Study ID Numbers: | 2008P000107 |
| Study First Received: | December 1, 2009 |
| Last Updated: | January 4, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by American Academy of Neurology:
|
epilepsy memory memantine localization related epilepsy focal epilepsy |
Additional relevant MeSH terms:
|
Epilepsy Epilepsies, Partial Memory Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases Neurobehavioral Manifestations Neurologic Manifestations Signs and Symptoms 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 May 23, 2013