<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/NCT02227056</url>
  </required_header>
  <id_info>
    <org_study_id>loe130007ctil</org_study_id>
    <nct_id>NCT02227056</nct_id>
  </id_info>
  <brief_title>Effect of Methylphenidate on Ecologic Function in Paediatric Acquired Brain Injury Population</brief_title>
  <official_title>Effect of Methylphenidate on Ecologic Function in Paediatric Acquired Brain Injury Population</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Loewenstein Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Loewenstein Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate the influence of Methylphenidate in pediatric&#xD;
      acquired brain injury population, regarding ecologic (every day) function. It is hypothesized&#xD;
      that the function with treatment will improve when compared to function without treatment in&#xD;
      the same patient. Improvement is expected by shortening time of execution in each specific&#xD;
      task and by reduction of the amount of assistance needed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Attention deficits in patients with acquired brain injury (ABI) are one of the most common&#xD;
      cognitive disorders acquainted. Prevalence of attention deficits after cerebrovascular&#xD;
      accident (CVA) varies between 20-58%, and after traumatic brain injury (TBI) may range up to&#xD;
      60% Methylphenidate (MPH) is a central nervous system (CNS) stimulant. In the CNS it&#xD;
      increases release and blocks reuptake of dopamine and noradrenalin, resulting in increased&#xD;
      synaptic and extracellular concentrations. Methylphenidate (MPH), act at the D1 and&#xD;
      α2-adrenergic receptors to facilitate effects on prefrontal cortical modulation of attention&#xD;
      and working memory .Methylphenidate has been used effectively and safely for treatment of&#xD;
      attention deficit hyperactivity disorder for many decades. The use of Methylphenidate to&#xD;
      enhance attention in disorders following TBI has been proposed as &quot;rational pharmacotherapy&quot;.&#xD;
      It demonstrated improvement in response speed, in adult patients with chronic TBI. In&#xD;
      pediatric population suffering Acquired brain injury there are scarce works regarding&#xD;
      methylphenidate short or long term efficacy. Since there are scarce reports altogether on&#xD;
      Methylphenidate's effect in pediatric Acquired brain injury population and since the studies&#xD;
      up to now examined the effectiveness in neuropsychological batteries we find it of interest&#xD;
      to examine the effect of Methylphenidate in ecological tasks, thus achieving a better&#xD;
      understanding of its possible effect in this subpopulation.&#xD;
&#xD;
      STUDY ASSUMPTIONS:&#xD;
&#xD;
        1. Methylphenidate has a proved safety profile in pediatric population suffering from&#xD;
           primary attention deficit hyperactivity disorder or secondary attention deficit&#xD;
           hyperactivity disorder .&#xD;
&#xD;
        2. Methylphenidate has positive influence on attentional disorders in pediatric population&#xD;
           suffering from Acquired brain injury in subacute and chronic phases.&#xD;
&#xD;
        3. Methylphenidate can enhance function of children with attentional disturbances secondary&#xD;
           to Acquired brain injury in different everyday tasks.&#xD;
&#xD;
        4. Methylphenidate can improve learning in pediatric population suffering from secondary&#xD;
           attention deficit hyperactivity disorder after Acquired brain injury, during subacute&#xD;
           rehabilitation period.&#xD;
&#xD;
      STUDY POPULATION:&#xD;
&#xD;
      The study is designed to include up to 40 children, aged 4-18 years, suffering attentional&#xD;
      disturbances secondary to Acquired Brain Injury (CVA, TBI, Anoxic brain injury, Central&#xD;
      Nervous System infections). Participants will be children hospitalized (inpatient or&#xD;
      outpatient) for rehabilitation in Loewenstein Rehabilitation Center Hospital, with no&#xD;
      contraindications for Methylphenidate treatment after their legal guardian gave informed&#xD;
      consent for participation.&#xD;
&#xD;
      STUDY METHODS:&#xD;
&#xD;
        1. Before inclusion each participant will undergo:&#xD;
&#xD;
             1. ECG&#xD;
&#xD;
             2. A screened computed exam to prove attentional disturbances with the Test of&#xD;
                Variables of Attention (TOVA) test.&#xD;
&#xD;
        2. Each participant will be tested on each task twice in two week's period: twice without&#xD;
           treatment of Methylphenidate and twice with Methylphenidate treatment.&#xD;
&#xD;
        3. Some participants will be retested after 7-14 days with no further treatment with&#xD;
           Methylphenidate, in order to estimate if influence of the drug on function continues&#xD;
           with no further treatment.&#xD;
&#xD;
        4. Drug will be given at least an hour and not more than 2.5 hours before being tested.&#xD;
&#xD;
        5. Drug dosage 0.3 milligram/kilo rounded to the nearest full milligram dosage will be&#xD;
           given a total of 3 times: once before Test of Variables of Attention (TOVA) exam under&#xD;
           Methylphenidate, and two other days while the participant is tested on the different&#xD;
           tasks.&#xD;
&#xD;
        6. Testing will be done in two hours of treatment session on different days.&#xD;
&#xD;
        7. Each participant will undergo the following tasks, in a consecutive order:&#xD;
&#xD;
             1. Dressing -T-shirt. Burden of care graded by scales of The Functional Independence&#xD;
                Measure (FIM) or the Functional Independence Measure for Children (WeeFIM)&#xD;
                according to age of participant.&#xD;
&#xD;
             2. Puzzle construction. Two different puzzles to avoid a possibility of learning. Both&#xD;
                the same level according to Sheridan's developmental norms.&#xD;
&#xD;
             3. Mathematical age appropriate working sheet.&#xD;
&#xD;
             4. Interactive social game such as memory game. On this task each participant will be&#xD;
                scored according to number of reminders given for his round or inhibition and his&#xD;
                emotional reaction to winning /loosing the game on a scale of 1-5, 1 being&#xD;
                appropriate reaction, 5 being highest frustration.&#xD;
&#xD;
        8. The Occupational therapist scoring the child's abilities and amount assistance needed&#xD;
           will be blindfolded to the treatment (given or not).&#xD;
&#xD;
      Performance data in each task will be collected with regard to duration for completion,&#xD;
      amount of assistance needed, impulsivity, long term and short term attention etc, and&#xD;
      statistically analyzed. Each participant (without Methylphenidate treatment) will serve as&#xD;
      control to data collected in the same tasks completed under treatment with Methylphenidate .&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2014</start_date>
  <completion_date type="Actual">March 1, 2017</completion_date>
  <primary_completion_date type="Actual">January 30, 2017</primary_completion_date>
  <phase>Phase 2</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Measure time (in minutes and seconds) and the amount of assistance needed (number of times each participant needed assistance) to complete the different tasks.</measure>
    <time_frame>After each task is completed time of the specific task will be recorded. Each participant will be tested 6 times 45 minutes during 3 weeks and will be followed for duration of hospital stay an expected average of 1 month</time_frame>
    <description>Measure the effect of Methylphenidate on function (in everyday tasks like dressing) of children with acquired brain injury</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Acquired Brain Injury</condition>
  <arm_group>
    <arm_group_label>Methylphenidate treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>On three different days each participant will receive Methylphenidate in a dosage of 0.3 milligram/kilo rounded to the nearest full milligram dosage</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>On three different days each participant will be re-evaluated without recieveing Methylphenidate.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methylphenidate</intervention_name>
    <description>On three different days each participant will receive Methylphenidate in a dosage of 0.3 milligram/kilo rounded to the nearest full milligram dosage</description>
    <arm_group_label>Methylphenidate treatment</arm_group_label>
    <other_name>Ritalin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female.&#xD;
&#xD;
          2. Ages 4-18 years old.&#xD;
&#xD;
          3. No contraindications for Methylphenidate treatment such as hypersensitivity, cardiac&#xD;
             disturbances unbalanced seizures etc'.&#xD;
&#xD;
          4. Informed consent given by their legal guardian.&#xD;
&#xD;
          5. Acquired brain injury&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Refusal to participate by either guardian or child.&#xD;
&#xD;
          2. No attentional disturbances in a computed screening exam: &quot;TOVA&quot;.&#xD;
&#xD;
          3. Medical contraindications to treatment with Methylphenidate such as short QT syndrome.&#xD;
&#xD;
          4. Side effects due to treatment with Methylphenidate.&#xD;
&#xD;
          5. Under medical treatment of medications enhancing dopamine/ noradrenaline release such&#xD;
             as Amantadine.&#xD;
&#xD;
          6. Unable to participate in tasks planned due to severe motor or cognitive disabilities.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>4 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sharon Shaklai, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Loewenstein Hospital Rehabilitation Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sigal Greenbaum, Master</last_name>
    <role>Study Director</role>
    <affiliation>Loewenstein Hospital Rehabiltation Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Loewenstein Rehabilitation Hospital Center</name>
      <address>
        <city>Raanana</city>
        <zip>43100</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <reference>
    <citation>Willmott C, Ponsford J. Efficacy of methylphenidate in the rehabilitation of attention following traumatic brain injury: a randomised, crossover, double blind, placebo controlled inpatient trial. J Neurol Neurosurg Psychiatry. 2009 May;80(5):552-7. doi: 10.1136/jnnp.2008.159632. Epub 2008 Dec 5.</citation>
    <PMID>19060022</PMID>
  </reference>
  <reference>
    <citation>Hornyak JE, Nelson VS, Hurvitz EA. The use of methylphenidate in paediatric traumatic brain injury. Pediatr Rehabil. 1997 Jan-Mar;1(1):15-7. doi: 10.3109/17518429709060937.</citation>
    <PMID>9689233</PMID>
  </reference>
  <reference>
    <citation>Whyte J, Hart T, Schuster K, Fleming M, Polansky M, Coslett HB. Effects of methylphenidate on attentional function after traumatic brain injury. A randomized, placebo-controlled trial. Am J Phys Med Rehabil. 1997 Nov-Dec;76(6):440-50. doi: 10.1097/00002060-199711000-00002.</citation>
    <PMID>9431261</PMID>
  </reference>
  <reference>
    <citation>Whyte J, Hart T, Vaccaro M, Grieb-Neff P, Risser A, Polansky M, Coslett HB. Effects of methylphenidate on attention deficits after traumatic brain injury: a multidimensional, randomized, controlled trial. Am J Phys Med Rehabil. 2004 Jun;83(6):401-20. doi: 10.1097/01.phm.0000128789.75375.d3.</citation>
    <PMID>15166683</PMID>
  </reference>
  <reference>
    <citation>Wheaton P, Mathias JL, Vink R. Impact of pharmacological treatments on cognitive and behavioral outcome in the postacute stages of adult traumatic brain injury: a meta-analysis. J Clin Psychopharmacol. 2011 Dec;31(6):745-57. doi: 10.1097/JCP.0b013e318235f4ac.</citation>
    <PMID>22020351</PMID>
  </reference>
  <reference>
    <citation>Mahalick DM, Carmel PW, Greenberg JP, Molofsky W, Brown JA, Heary RF, Marks D, Zampella E, Hodosh R, von der Schmidt E 3rd. Psychopharmacologic treatment of acquired attention disorders in children with brain injury. Pediatr Neurosurg. 1998 Sep;29(3):121-6. doi: 10.1159/000028705.</citation>
    <PMID>9838263</PMID>
  </reference>
  <verification_date>September 2018</verification_date>
  <study_first_submitted>July 1, 2014</study_first_submitted>
  <study_first_submitted_qc>August 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 27, 2014</study_first_posted>
  <last_update_submitted>February 25, 2019</last_update_submitted>
  <last_update_submitted_qc>February 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 26, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Acquired pediatric brain injury</keyword>
  <keyword>Methylphenidate</keyword>
  <keyword>Traumatic brain injury</keyword>
  <keyword>Cerebrovascular event</keyword>
  <keyword>Hypoxic ischemic brain injury</keyword>
  <keyword>Function (ecologic)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methylphenidate</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/NCT02227056
org study id: loe130007ctil
nct id: NCT02227056
lead sponsor: 
has dmc: Yes
The purpose of this study is to investigate the influence of Methylphenidate in pediatric
      acquired brain injury population, regarding ecologic (every day) function. It is hypothesized
      that the function with treatment will improve when compared to function without treatment in
      the same patient. Improvement is expected by shortening time of execution in each specific
      task and by reduction of the amount of assistance needed.
Attention deficits in patients with acquired brain injury (ABI) are one of the most common
      cognitive disorders acquainted. Prevalence of attention deficits after cerebrovascular
      accident (CVA) varies between 20-58%, and after traumatic brain injury (TBI) may range up to
      60% Methylphenidate (MPH) is a central nervous system (CNS) stimulant. In the CNS it
      increases release and blocks reuptake of dopamine and noradrenalin, resulting in increased
      synaptic and extracellular concentrations. Methylphenidate (MPH), act at the D1 and
      α2-adrenergic receptors to facilitate effects on prefrontal cortical modulation of attention
      and working memory .Methylphenidate has been used effectively and safely for treatment of
      attention deficit hyperactivity disorder for many decades. The use of Methylphenidate to
      enhance attention in disorders following TBI has been proposed as "rational pharmacotherapy".
      It demonstrated improvement in response speed, in adult patients with chronic TBI. In
      pediatric population suffering Acquired brain injury there are scarce works regarding
      methylphenidate short or long term efficacy. Since there are scarce reports altogether on
      Methylphenidate's effect in pediatric Acquired brain injury population and since the studies
      up to now examined the effectiveness in neuropsychological batteries we find it of interest
      to examine the effect of Methylphenidate in ecological tasks, thus achieving a better
      understanding of its possible effect in this subpopulation.

      STUDY ASSUMPTIONS:

        1. Methylphenidate has a proved safety profile in pediatric population suffering from
           primary attention deficit hyperactivity disorder or secondary attention deficit
           hyperactivity disorder .

        2. Methylphenidate has positive influence on attentional disorders in pediatric population
           suffering from Acquired brain injury in subacute and chronic phases.

        3. Methylphenidate can enhance function of children with attentional disturbances secondary
           to Acquired brain injury in different everyday tasks.

        4. Methylphenidate can improve learning in pediatric population suffering from secondary
           attention deficit hyperactivity disorder after Acquired brain injury, during subacute
           rehabilitation period.

      STUDY POPULATION:

      The study is designed to include up to 40 children, aged 4-18 years, suffering attentional
      disturbances secondary to Acquired Brain Injury (CVA, TBI, Anoxic brain injury, Central
      Nervous System infections). Participants will be children hospitalized (inpatient or
      outpatient) for rehabilitation in Loewenstein Rehabilitation Center Hospital, with no
      contraindications for Methylphenidate treatment after their legal guardian gave informed
      consent for participation.

      STUDY METHODS:

        1. Before inclusion each participant will undergo:

             1. ECG

             2. A screened computed exam to prove attentional disturbances with the Test of
                Variables of Attention (TOVA) test.

        2. Each participant will be tested on each task twice in two week's period: twice without
           treatment of Methylphenidate and twice with Methylphenidate treatment.

        3. Some participants will be retested after 7-14 days with no further treatment with
           Methylphenidate, in order to estimate if influence of the drug on function continues
           with no further treatment.

        4. Drug will be given at least an hour and not more than 2.5 hours before being tested.

        5. Drug dosage 0.3 milligram/kilo rounded to the nearest full milligram dosage will be
           given a total of 3 times: once before Test of Variables of Attention (TOVA) exam under
           Methylphenidate, and two other days while the participant is tested on the different
           tasks.

        6. Testing will be done in two hours of treatment session on different days.

        7. Each participant will undergo the following tasks, in a consecutive order:

             1. Dressing -T-shirt. Burden of care graded by scales of The Functional Independence
                Measure (FIM) or the Functional Independence Measure for Children (WeeFIM)
                according to age of participant.

             2. Puzzle construction. Two different puzzles to avoid a possibility of learning. Both
                the same level according to Sheridan's developmental norms.

             3. Mathematical age appropriate working sheet.

             4. Interactive social game such as memory game. On this task each participant will be
                scored according to number of reminders given for his round or inhibition and his
                emotional reaction to winning /loosing the game on a scale of 1-5, 1 being
                appropriate reaction, 5 being highest frustration.

        8. The Occupational therapist scoring the child's abilities and amount assistance needed
           will be blindfolded to the treatment (given or not).

      Performance data in each task will be collected with regard to duration for completion,
      amount of assistance needed, impulsivity, long term and short term attention etc, and
      statistically analyzed. Each participant (without Methylphenidate treatment) will serve as
      control to data collected in the same tasks completed under treatment with Methylphenidate .
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Measure time (in minutes and seconds) and the amount of assistance needed (number of times each participant needed assistance) to complete the different tasks.
time frame: After each task is completed time of the specific task will be recorded. Each participant will be tested 6 times 45 minutes during 3 weeks and will be followed for duration of hospital stay an expected average of 1 month
description: Measure the effect of Methylphenidate on function (in everyday tasks like dressing) of children with acquired brain injury
arm group label: Methylphenidate treatment
arm group type: Experimental
description: On three different days each participant will receive Methylphenidate in a dosage of 0.3 milligram/kilo rounded to the nearest full milligram dosage
arm group label: Control
arm group type: No Intervention
description: On three different days each participant will be re-evaluated without recieveing Methylphenidate.
intervention type: Drug
intervention name: Methylphenidate
description: On three different days each participant will receive Methylphenidate in a dosage of 0.3 milligram/kilo rounded to the nearest full milligram dosage
arm group label: Methylphenidate treatment
other name: Ritalin
criteria: 
gender: All
minimum age: 4 Years
maximum age: 18 Years
healthy volunteers: No
last name: Sharon Shaklai, Dr
role: Principal Investigator
affiliation: Loewenstein Hospital Rehabilitation Center
last name: Sigal Greenbaum, Master
role: Study Director
affiliation: Loewenstein Hospital Rehabiltation Center
facility: 
country: Israel
citation: Willmott C, Ponsford J. Efficacy of methylphenidate in the rehabilitation of attention following traumatic brain injury: a randomised, crossover, double blind, placebo controlled inpatient trial. J Neurol Neurosurg Psychiatry. 2009 May;80(5):552-7. doi: 10.1136/jnnp.2008.159632. Epub 2008 Dec 5.
PMID: 19060022
citation: Hornyak JE, Nelson VS, Hurvitz EA. The use of methylphenidate in paediatric traumatic brain injury. Pediatr Rehabil. 1997 Jan-Mar;1(1):15-7. doi: 10.3109/17518429709060937.
PMID: 9689233
citation: Whyte J, Hart T, Schuster K, Fleming M, Polansky M, Coslett HB. Effects of methylphenidate on attentional function after traumatic brain injury. A randomized, placebo-controlled trial. Am J Phys Med Rehabil. 1997 Nov-Dec;76(6):440-50. doi: 10.1097/00002060-199711000-00002.
PMID: 9431261
citation: Whyte J, Hart T, Vaccaro M, Grieb-Neff P, Risser A, Polansky M, Coslett HB. Effects of methylphenidate on attention deficits after traumatic brain injury: a multidimensional, randomized, controlled trial. Am J Phys Med Rehabil. 2004 Jun;83(6):401-20. doi: 10.1097/01.phm.0000128789.75375.d3.
PMID: 15166683
citation: Wheaton P, Mathias JL, Vink R. Impact of pharmacological treatments on cognitive and behavioral outcome in the postacute stages of adult traumatic brain injury: a meta-analysis. J Clin Psychopharmacol. 2011 Dec;31(6):745-57. doi: 10.1097/JCP.0b013e318235f4ac.
PMID: 22020351
citation: Mahalick DM, Carmel PW, Greenberg JP, Molofsky W, Brown JA, Heary RF, Marks D, Zampella E, Hodosh R, von der Schmidt E 3rd. Psychopharmacologic treatment of acquired attention disorders in children with brain injury. Pediatr Neurosurg. 1998 Sep;29(3):121-6. doi: 10.1159/000028705.
PMID: 9838263
responsible party type: Sponsor
mesh term: Brain Injuries
mesh term: Wounds and Injuries
mesh term: Methylphenidate