<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03779672</url>
  </required_header>
  <id_info>
    <org_study_id>22838</org_study_id>
    <nct_id>NCT03779672</nct_id>
  </id_info>
  <brief_title>Memantine for Epileptic Encephalopathy</brief_title>
  <official_title>Randomized Double-blind Placebo-controlled Trial of Memantine Hydrochloride for the Treatment of Childhood-onset Epileptic Encephalopathies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kenneth Myers, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>McGill University Health Centre/Research Institute of the McGill University Health Centre</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the potential benefit of memantine hydrochloride as treatment for&#xD;
      children with epileptic encephalopathy using a double-blind placebo-controlled cross-over&#xD;
      design.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Memantine, a drug approved for Alzheimer's dementia, exerts its therapeutic effect through&#xD;
      its action as a low to moderate affinity non-competitive (open channel) N-methyl-D-aspartate&#xD;
      receptor (NMDA-R) antagonist, which binds preferentially to the NMDA receptor-operated cation&#xD;
      channels. It blocks the effects of persistently elevated levels of glutamate that may lead to&#xD;
      neuronal dysfunction. Memantine may also have anti-inflammatory effects. Memantine has been&#xD;
      used off-label in children and adolescents with autism spectrum disorder, to improve the&#xD;
      cognitive impairment.&#xD;
&#xD;
      Epileptic encephalopathy, as well as other forms of epilepsy, may occur as a result of&#xD;
      multiple etiologies, including genetic and inflammatory pathologies. Ion channels were long&#xD;
      considered to be implicated in genetic epilepsy. Indeed one of the many possible causes of&#xD;
      epilepsy is NMDA receptor dysfunction.&#xD;
&#xD;
      In the present study, the investigators plan to investigate the potential benefit of&#xD;
      memantine as a treatment for epileptic encephalopathy. A double-blind placebo-controlled&#xD;
      cross-over design will be used, with participants receiving 6 weeks of memantine and 6 weeks&#xD;
      of placebo, with a 2-week washout period in between.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 7, 2019</start_date>
  <completion_date type="Actual">February 8, 2022</completion_date>
  <primary_completion_date type="Actual">November 8, 2021</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Monocentric, Off-Label Use, Randomized, crossover, Double-blinded Placebo vs Memantine.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double-blinded Placebo vs Memantine</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of Responder versus Non-Responder Status with Memantine</measure>
    <time_frame>Week 6 or 14</time_frame>
    <description>&quot;Responder&quot; defined as having ≥ 2 of (1) EEG improvement, (2) decreased seizure frequency, (3) cognitive improvement, (4) caregiver impression of improvement, (5) Serum Inflammatory Markers Change. These outcomes are individually defined in detail in the secondary outcomes below.&#xD;
Description of the primary variable(s) The primary efficacy endpoint is the composite cluster of the first occurrence, over the duration of study (randomization to study end date inclusive), of the EE improvement.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rate of Responder versus Non-Responder Status with Placebo</measure>
    <time_frame>Week 6 or 14</time_frame>
    <description>&quot;Responder&quot; defined as having ≥ 2 of (1) EEG improvement, (2) decreased seizure frequency, (3) cognitive improvement, (4) caregiver impression of improvement, (5) Serum Inflammatory Markers Change. These outcomes are individually defined in detail in the secondary outcomes below.&#xD;
Description of the primary variable(s) The primary efficacy endpoint is the composite cluster of the first occurrence, over the duration of study (randomization to study end date inclusive), of the EE improvement.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>EEG Change with Memantine</measure>
    <time_frame>Week 6 or 14</time_frame>
    <description>EEG improvement EEG Change: EEG is not a quantitative measure, and there are many possible different patterns that may be seen in epileptic encephalopathy. In general, improvement usually involves (a) background activity changing to more closely resemble the expected background activity for the patient's age, and/or (b) decrease in frequency of epileptiform activity. The electroencephalographer will compare EEGs to the baseline study, and will score as (1) Interval worsening, (2) No significant change, or (3) Interval improvement.&#xD;
We will be assessing all the frequencies usually assessed on a routine EEG (delta, theta, alpha and beta). The frequency range assessed will be 1-70 Hz.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EEG Change with Placebo</measure>
    <time_frame>Week 6 or 14</time_frame>
    <description>EEG Change: EEG is not a quantitative measure, and there are many possible different patterns that may be seen in epileptic encephalopathy. In general, improvement usually involves (a) background activity changing to more closely resemble the expected background activity for the patient's age, and/or (b) decrease in frequency of epileptiform activity. The electroencephalographer will compare EEGs to the baseline study, and will score as (1) Interval worsening, (2) No significant change, or (3) Interval improvement.&#xD;
EEG improvement We will be assessing all the frequencies usually assessed on a routine EEG (delta, theta, alpha and beta). The frequency range assessed will be 1-70 Hz.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Seizure Frequency Change with Memantine</measure>
    <time_frame>Week 6 or 14</time_frame>
    <description>Reduction in seizure frequency Seizure Frequency Change: Participants will keep seizure diaries throughout the study. If the frequency of seizures decreases by &gt; 50% from the baseline frequency, they will be classified as having a significant reduction in seizure frequency.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Seizure Frequency Change with Placebo</measure>
    <time_frame>Week 6 or 14</time_frame>
    <description>Reduction in seizure frequency Seizure Frequency Change: Participants will keep seizure diaries throughout the study. If the frequency of seizures decreases by &gt; 50% from the baseline frequency, they will be classified as having a significant reduction in seizure frequency.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive Function Change with Memantine</measure>
    <time_frame>Week 6 or 14</time_frame>
    <description>Definite improvement in cognitive functioning by neuropsychological testing Cognitive Cognitive Function Change: Participants will see a neuropsychologist at baseline and at the conclusion of each treatment period. The precise testing used will be to the discretion of the neuropsychologist, based on the participant's cognitive capabilities. The neuropsychologist will compare to the baseline assessment and determine if there has been a significant change, based on her experience using these testing protocols in the given age range. The neuropsychologist will score as (1) Interval worsening, (2) No significant change, or (3) Interval improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive Function Change with Placebo</measure>
    <time_frame>Week 6 or 14</time_frame>
    <description>Definite improvement in cognitive functioning by neuropsychological testing Cognitive Cognitive Function Change: Participants will see a neuropsychologist at baseline and at the conclusion of each treatment period. The precise testing used will be to the discretion of the neuropsychologist, based on the participant's cognitive capabilities. The neuropsychologist will compare to the baseline assessment and determine if there has been a significant change, based on her experience using these testing protocols in the given age range. The neuropsychologist will score as (1) Interval worsening, (2) No significant change, or (3) Interval improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Caregiver Impression of Change with Memantine</measure>
    <time_frame>Week 6 or 14</time_frame>
    <description>Subjective perception of improvement by parents Caregiver Impression of Change: At the conclusion of each treatment period, caregivers will be asked the following question: &quot;Compared to before the study, do you feel the overall functioning of your child (including seizure control, development and quality of life) is (1) Improved, (2) No Change, or (3) Worsened.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Caregiver Impression of Change with Placebo</measure>
    <time_frame>Week 6 or 14</time_frame>
    <description>Subjective perception of improvement by parents Caregiver Impression of Change: At the conclusion of each treatment period, caregivers will be asked the following question: &quot;Compared to before the study, do you feel the overall functioning of your child (including seizure control, development and quality of life) is (1) Improved, (2) No Change, or (3) Worsened.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Inflammatory Markers Change with Memantine</measure>
    <time_frame>Week 6 or 14</time_frame>
    <description>Changes in serum inflammation Serum inflammatory markers: C Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR) and interleukin-6 (IL-6). CRP and ESR are commonly-used clinical measures of inflammation, and IL-6 was found to be elevated in some epileptic encephalopathies in one study (van den Munckhof et al., 2016). Levels will be compared following each treatment period, to the baseline value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Inflammatory Markers Change with Placebo</measure>
    <time_frame>Week 6 or 14</time_frame>
    <description>Changes in serum inflammation Serum inflammatory markers: C Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR) and interleukin-6 (IL-6). CRP and ESR are commonly-used clinical measures of inflammation, and IL-6 was found to be elevated in some epileptic encephalopathies in one study (van den Munckhof et al., 2016). Levels will be compared following each treatment period, to the baseline value.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Adverse events</measure>
    <time_frame>Week 16</time_frame>
    <description>Participants will be asked at all visits to report any possible adverse events, including those requiring emergent treatment. Adverse events will be classified as &quot;clinically significant&quot; or &quot;not clinically significant&quot; with respect to the likelihood that they are related to use of the investigational drug. The frequency of adverse events will be determined during the period receiving memantine and the period receiving placebo.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Epileptic Encephalopathy, Childhood-Onset</condition>
  <arm_group>
    <arm_group_label>Memantine Hydrochloride 10 mg Placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Blue colour capsules, for oral administration, containing 5 mg of active memantine or matching placebo for oral administration.&#xD;
Dose regimen:&#xD;
Memantine Hydrochloride&#xD;
Week #1: 5 mg id (am), 1 caps&#xD;
Week #2: 5 mg bid (am and pm), 2 caps&#xD;
Weeks #3-6: 5 mg am &amp; 2x 5 mg pm, 3 caps&#xD;
Washout (Weeks #7-8)&#xD;
Placebo&#xD;
Week #9: id (am), 1 caps&#xD;
Week #10: bid (am and pm), 2 caps&#xD;
Weeks #11-14: 1 caps am &amp; 2 caps pm, 3 caps</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Memantine Hydrochloride 10 mg</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo&#xD;
Week #1: id (am), 1 caps&#xD;
Week #2: bid (am and pm), 2 caps&#xD;
Weeks #3-6: 1 caps am &amp; 2 caps pm, 3 caps&#xD;
Washout (Weeks #7-8) Memantine Hydrochloride&#xD;
Week #9: 5 mg id (am), 1 caps&#xD;
Week #10: 5 mg bid (am and pm), 2 caps&#xD;
Weeks #11-14: 5 mg am &amp; 2x 5 mg pm, 3 caps</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Memantine Hydrochloride 10 mg</intervention_name>
    <description>Week #1: 5 mg id (am), 1 caps&#xD;
Week #2: 5 mg bid (am and pm), 2 caps&#xD;
Weeks #3-6: 5 mg am &amp; 2x 5 mg pm, 3 caps&#xD;
Weeks #7-8: Washout&#xD;
Placebo&#xD;
Week #9: id (am), 1 caps&#xD;
Week #10: bid (am and pm), 2 caps&#xD;
Weeks #11-14: 1 caps am &amp; 2 caps pm, 3 caps&#xD;
OR Placebo&#xD;
Week #1: id (am), 1 caps&#xD;
Week #2: bid (am and pm), 2 caps&#xD;
Weeks #3-6: 1 caps am &amp; 2 caps pm, 3 caps&#xD;
Weeks #7-8: Washout&#xD;
Memantine&#xD;
Week #9: 5 mg id (am), 1 caps&#xD;
Week #10: 5 mg bid (am and pm), 2 caps&#xD;
Weeks #11-14: 5 mg am &amp; 2x 5 mg pm, 3 caps</description>
    <arm_group_label>Memantine Hydrochloride 10 mg Placebo</arm_group_label>
    <arm_group_label>Placebo Memantine Hydrochloride 10 mg</arm_group_label>
    <other_name>PrSANDOZ MEMANTINE FCT10 mg Drug Identification Number (DIN) 02375532</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent obtained&#xD;
&#xD;
          -  Age 6-18 years (Weight ≥ 20 kg)&#xD;
&#xD;
          -  Clinical diagnosis of epileptic encephalopathy&#xD;
&#xD;
               -  Subject with epilepsy and developmental impairment;&#xD;
&#xD;
               -  Epileptic activity itself contributes to severe cognitive and behavioural&#xD;
                  impairments&#xD;
&#xD;
               -  Patients will typically have already have trialed at least two standard therapies&#xD;
&#xD;
          -  Females of childbearing age:&#xD;
&#xD;
          -  Negative urinary pregnancy test at screening&#xD;
&#xD;
          -  Agree to use effective contraception for the duration of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability of a parent or legal guardian to give informed consent for any reason.&#xD;
&#xD;
          -  Known hypersensitivity to memantine hydrochloride&#xD;
&#xD;
          -  Taking concomitant Amantadine, Ketamine or Dextromethorphan, Cimetidine, Ranitidine,&#xD;
             Procainamide, Quinidine, Quinine, Hydrochlorothiazide, Anticholinergics, L-dopa,&#xD;
             Anticoagulant,&#xD;
&#xD;
          -  Any degree of renal impairment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Children Hospital - MUHC</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H4A 3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>van den Munckhof B, de Vries EE, Braun KP, Boss HM, Willemsen MA, van Royen-Kerkhof A, de Jager W, Jansen FE. Serum inflammatory mediators correlate with disease activity in electrical status epilepticus in sleep (ESES) syndrome. Epilepsia. 2016 Feb;57(2):e45-50. doi: 10.1111/epi.13274. Epub 2015 Dec 14.</citation>
    <PMID>26666401</PMID>
  </reference>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>December 5, 2018</study_first_submitted>
  <study_first_submitted_qc>December 17, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>March 10, 2022</last_update_submitted>
  <last_update_submitted_qc>March 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 11, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>McGill University Health Centre/Research Institute of the McGill University Health Centre</investigator_affiliation>
    <investigator_full_name>Kenneth Myers, MD</investigator_full_name>
    <investigator_title>Assistant Professor (Clinical), Neurologist Pediatrician</investigator_title>
  </responsible_party>
  <keyword>Memantine</keyword>
  <keyword>N-methyl-D-aspartate receptor</keyword>
  <keyword>Serum inflammatory</keyword>
  <keyword>Seizure</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Diseases</mesh_term>
    <mesh_term>Epilepsy</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Memantine</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03779672
org study id: 22838
nct id: NCT03779672
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will evaluate the potential benefit of memantine hydrochloride as treatment for
      children with epileptic encephalopathy using a double-blind placebo-controlled cross-over
      design.
Memantine, a drug approved for Alzheimer's dementia, exerts its therapeutic effect through
      its action as a low to moderate affinity non-competitive (open channel) N-methyl-D-aspartate
      receptor (NMDA-R) antagonist, which binds preferentially to the NMDA receptor-operated cation
      channels. It blocks the effects of persistently elevated levels of glutamate that may lead to
      neuronal dysfunction. Memantine may also have anti-inflammatory effects. Memantine has been
      used off-label in children and adolescents with autism spectrum disorder, to improve the
      cognitive impairment.

      Epileptic encephalopathy, as well as other forms of epilepsy, may occur as a result of
      multiple etiologies, including genetic and inflammatory pathologies. Ion channels were long
      considered to be implicated in genetic epilepsy. Indeed one of the many possible causes of
      epilepsy is NMDA receptor dysfunction.

      In the present study, the investigators plan to investigate the potential benefit of
      memantine as a treatment for epileptic encephalopathy. A double-blind placebo-controlled
      cross-over design will be used, with participants receiving 6 weeks of memantine and 6 weeks
      of placebo, with a 2-week washout period in between.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Monocentric, Off-Label Use, Randomized, crossover, Double-blinded Placebo vs Memantine.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double-blinded Placebo vs Memantine
measure: Rate of Responder versus Non-Responder Status with Memantine
time frame: Week 6 or 14
description: "Responder" defined as having ≥ 2 of (1) EEG improvement, (2) decreased seizure frequency, (3) cognitive improvement, (4) caregiver impression of improvement, (5) Serum Inflammatory Markers Change. These outcomes are individually defined in detail in the secondary outcomes below.
Description of the primary variable(s) The primary efficacy endpoint is the composite cluster of the first occurrence, over the duration of study (randomization to study end date inclusive), of the EE improvement.
measure: Rate of Responder versus Non-Responder Status with Placebo
time frame: Week 6 or 14
description: "Responder" defined as having ≥ 2 of (1) EEG improvement, (2) decreased seizure frequency, (3) cognitive improvement, (4) caregiver impression of improvement, (5) Serum Inflammatory Markers Change. These outcomes are individually defined in detail in the secondary outcomes below.
Description of the primary variable(s) The primary efficacy endpoint is the composite cluster of the first occurrence, over the duration of study (randomization to study end date inclusive), of the EE improvement.
measure: EEG Change with Memantine
time frame: Week 6 or 14
description: EEG improvement EEG Change: EEG is not a quantitative measure, and there are many possible different patterns that may be seen in epileptic encephalopathy. In general, improvement usually involves (a) background activity changing to more closely resemble the expected background activity for the patient's age, and/or (b) decrease in frequency of epileptiform activity. The electroencephalographer will compare EEGs to the baseline study, and will score as (1) Interval worsening, (2) No significant change, or (3) Interval improvement.
We will be assessing all the frequencies usually assessed on a routine EEG (delta, theta, alpha and beta). The frequency range assessed will be 1-70 Hz.
measure: EEG Change with Placebo
time frame: Week 6 or 14
description: EEG Change: EEG is not a quantitative measure, and there are many possible different patterns that may be seen in epileptic encephalopathy. In general, improvement usually involves (a) background activity changing to more closely resemble the expected background activity for the patient's age, and/or (b) decrease in frequency of epileptiform activity. The electroencephalographer will compare EEGs to the baseline study, and will score as (1) Interval worsening, (2) No significant change, or (3) Interval improvement.
EEG improvement We will be assessing all the frequencies usually assessed on a routine EEG (delta, theta, alpha and beta). The frequency range assessed will be 1-70 Hz.
measure: Seizure Frequency Change with Memantine
time frame: Week 6 or 14
description: Reduction in seizure frequency Seizure Frequency Change: Participants will keep seizure diaries throughout the study. If the frequency of seizures decreases by > 50% from the baseline frequency, they will be classified as having a significant reduction in seizure frequency.
measure: Seizure Frequency Change with Placebo
time frame: Week 6 or 14
description: Reduction in seizure frequency Seizure Frequency Change: Participants will keep seizure diaries throughout the study. If the frequency of seizures decreases by > 50% from the baseline frequency, they will be classified as having a significant reduction in seizure frequency.
measure: Cognitive Function Change with Memantine
time frame: Week 6 or 14
description: Definite improvement in cognitive functioning by neuropsychological testing Cognitive Cognitive Function Change: Participants will see a neuropsychologist at baseline and at the conclusion of each treatment period. The precise testing used will be to the discretion of the neuropsychologist, based on the participant's cognitive capabilities. The neuropsychologist will compare to the baseline assessment and determine if there has been a significant change, based on her experience using these testing protocols in the given age range. The neuropsychologist will score as (1) Interval worsening, (2) No significant change, or (3) Interval improvement.
measure: Cognitive Function Change with Placebo
time frame: Week 6 or 14
description: Definite improvement in cognitive functioning by neuropsychological testing Cognitive Cognitive Function Change: Participants will see a neuropsychologist at baseline and at the conclusion of each treatment period. The precise testing used will be to the discretion of the neuropsychologist, based on the participant's cognitive capabilities. The neuropsychologist will compare to the baseline assessment and determine if there has been a significant change, based on her experience using these testing protocols in the given age range. The neuropsychologist will score as (1) Interval worsening, (2) No significant change, or (3) Interval improvement.
measure: Caregiver Impression of Change with Memantine
time frame: Week 6 or 14
description: Subjective perception of improvement by parents Caregiver Impression of Change: At the conclusion of each treatment period, caregivers will be asked the following question: "Compared to before the study, do you feel the overall functioning of your child (including seizure control, development and quality of life) is (1) Improved, (2) No Change, or (3) Worsened.
measure: Caregiver Impression of Change with Placebo
time frame: Week 6 or 14
description: Subjective perception of improvement by parents Caregiver Impression of Change: At the conclusion of each treatment period, caregivers will be asked the following question: "Compared to before the study, do you feel the overall functioning of your child (including seizure control, development and quality of life) is (1) Improved, (2) No Change, or (3) Worsened.
measure: Serum Inflammatory Markers Change with Memantine
time frame: Week 6 or 14
description: Changes in serum inflammation Serum inflammatory markers: C Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR) and interleukin-6 (IL-6). CRP and ESR are commonly-used clinical measures of inflammation, and IL-6 was found to be elevated in some epileptic encephalopathies in one study (van den Munckhof et al., 2016). Levels will be compared following each treatment period, to the baseline value.
measure: Serum Inflammatory Markers Change with Placebo
time frame: Week 6 or 14
description: Changes in serum inflammation Serum inflammatory markers: C Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR) and interleukin-6 (IL-6). CRP and ESR are commonly-used clinical measures of inflammation, and IL-6 was found to be elevated in some epileptic encephalopathies in one study (van den Munckhof et al., 2016). Levels will be compared following each treatment period, to the baseline value.
measure: Adverse events
time frame: Week 16
description: Participants will be asked at all visits to report any possible adverse events, including those requiring emergent treatment. Adverse events will be classified as "clinically significant" or "not clinically significant" with respect to the likelihood that they are related to use of the investigational drug. The frequency of adverse events will be determined during the period receiving memantine and the period receiving placebo.
arm group label: Memantine Hydrochloride 10 mg Placebo
arm group type: Active Comparator
description: Blue colour capsules, for oral administration, containing 5 mg of active memantine or matching placebo for oral administration.
Dose regimen:
Memantine Hydrochloride
Week #1: 5 mg id (am), 1 caps
Week #2: 5 mg bid (am and pm), 2 caps
Weeks #3-6: 5 mg am & 2x 5 mg pm, 3 caps
Washout (Weeks #7-8)
Placebo
Week #9: id (am), 1 caps
Week #10: bid (am and pm), 2 caps
Weeks #11-14: 1 caps am & 2 caps pm, 3 caps
arm group label: Placebo Memantine Hydrochloride 10 mg
arm group type: Placebo Comparator
description: Placebo
Week #1: id (am), 1 caps
Week #2: bid (am and pm), 2 caps
Weeks #3-6: 1 caps am & 2 caps pm, 3 caps
Washout (Weeks #7-8) Memantine Hydrochloride
Week #9: 5 mg id (am), 1 caps
Week #10: 5 mg bid (am and pm), 2 caps
Weeks #11-14: 5 mg am & 2x 5 mg pm, 3 caps
intervention type: Drug
intervention name: Memantine Hydrochloride 10 mg
description: Week #1: 5 mg id (am), 1 caps
Week #2: 5 mg bid (am and pm), 2 caps
Weeks #3-6: 5 mg am & 2x 5 mg pm, 3 caps
Weeks #7-8: Washout
Placebo
Week #9: id (am), 1 caps
Week #10: bid (am and pm), 2 caps
Weeks #11-14: 1 caps am & 2 caps pm, 3 caps
OR Placebo
Week #1: id (am), 1 caps
Week #2: bid (am and pm), 2 caps
Weeks #3-6: 1 caps am & 2 caps pm, 3 caps
Weeks #7-8: Washout
Memantine
Week #9: 5 mg id (am), 1 caps
Week #10: 5 mg bid (am and pm), 2 caps
Weeks #11-14: 5 mg am & 2x 5 mg pm, 3 caps
arm group label: Memantine Hydrochloride 10 mg Placebo
arm group label: Placebo Memantine Hydrochloride 10 mg
other name: PrSANDOZ MEMANTINE FCT10 mg Drug Identification Number (DIN) 02375532
criteria: 
gender: All
minimum age: 6 Years
maximum age: 18 Years
healthy volunteers: No
facility: 
country: Canada
citation: van den Munckhof B, de Vries EE, Braun KP, Boss HM, Willemsen MA, van Royen-Kerkhof A, de Jager W, Jansen FE. Serum inflammatory mediators correlate with disease activity in electrical status epilepticus in sleep (ESES) syndrome. Epilepsia. 2016 Feb;57(2):e45-50. doi: 10.1111/epi.13274. Epub 2015 Dec 14.
PMID: 26666401
responsible party type: Sponsor-Investigator
investigator affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
investigator full name: Kenneth Myers, MD
investigator title: Assistant Professor (Clinical), Neurologist Pediatrician
mesh term: Brain Diseases
mesh term: Epilepsy
mesh term: Memantine