Does Memantine Improve Verbal Memory Task Performance in Subjects With Partial Epilepsy and Memory Dysfunction?

NCT01054599 | Completed Results

• 1 other identifier: 2008P000107
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Epilepsy

Keywords

epilepsy; memory; memantine; localization related epilepsy; focal epilepsy

Outcome Measures

Primary Outcomes (1)

• The Change Scores in Memory Measures From Baseline to Post-treatment/Placebo Will be Compared Between the Memantine Treatment and Placebo Groups.

  Change scores from pre- to post-treatment/placebo were calculated for the primary outcome measures, the Selective Reminding Test Continuous Long-Term Retrieval (range 0-72; higher scores indicate better memory) and 7-24 Spatial Recall Test Total Learning (range 0-35; total correct across 5 learning trials are summed, with higher scores indicating better memory) scores. These measures are scores on a scale, rather than representing standard units.

  13 weeks

Secondary Outcomes (3)

• 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.

  5 years

• 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.

  5 years

• A Secondary Analysis Will Examine the Possible Sustained Benefit of Continued Memantine Use.

  26 weeks

Study Arms (2)

Memantine

EXPERIMENTAL

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

Sugar Pill

PLACEBO COMPARATOR

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

Interventions

Memantine DRUG

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.

Also known as: Namenda

Memantine

Sugar Pill OTHER

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).

Also known as: Placebo

Sugar Pill

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• American Academy of Neurology: lead
• Forest Laboratories: collaborator

Study Sites (3)

Emory University

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Newton-Wellesley Hospital

Newton, Massachusetts, 02462, United States

Location

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  PMID: 30449328 DERIVED

MeSH Terms

Conditions

Epilepsy; Epilepsies, Partial

Interventions

Memantine; Sugars

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Carbohydrates

Results Point of Contact

• Title: Beth Leeman-Markowski, MD
• Organization: VA New York Harbor Healthcare System, NYU

beth.leeman-markowski@nyumc.org

212-686-7500

Study Officials

• Lauren Moo, M.D.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant in Neuroscience

Study Record Dates

• First Submitted: December 1, 2009
• First Posted: January 22, 2010
• Study Start: January 1, 2009
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: July 11, 2017
• Results First Posted: July 11, 2017

Record last verified: 2017-06

Locations

US (3)