<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/NCT03811847</url>
  </required_header>
  <id_info>
    <org_study_id>2018P003099</org_study_id>
    <nct_id>NCT03811847</nct_id>
  </id_info>
  <brief_title>A Pilot of Methylphenidate in Mild Cognitive Impairment and Dementia Participants.</brief_title>
  <official_title>A Pilot, Multiple Crossover, Randomized Block Sequence, Double-Blind, Placebo-Controlled Trial for Use of Methylphenidate for Cognitive and Behavioral Symptoms in Mild Cognitive Impairment and Dementia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Investigators are doing this research study to find out if methylphenidate (MPH) can help&#xD;
      people with Mild Cognitive Impairment (MCI) or mild dementia likely due to Alzheimer's&#xD;
      Disease (AD) and related disorders (ADRD).&#xD;
&#xD;
      The study drug MPH is approved by the U.S. Food and Drug Administration (FDA) to treat&#xD;
      Attention Deficit/Hyperactivity Disorder (ADHD), but MPH is not approved by the FDA to treat&#xD;
      Mild Cognitive Impairment or mild dementia related to Alzheimer's Disease. However, other&#xD;
      studies have been done in which MPH has been given to people with neurodegenerative dementias&#xD;
      and results have shown some improvement in these people's mood and cognition. Investigators&#xD;
      would like to see if MPH will help mood and cognition.&#xD;
&#xD;
      This study will take place completely virtually (with the option to come in for the first&#xD;
      visit to meet the study team). All study visits will occur over a secure videoconferencing&#xD;
      platform. All study materials will be shipped directly to the home of each participant.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Investigators will give participants a supply of study drug. Participants will take the study&#xD;
      drug by mouth once a day for 16 weeks. It is important for participants to follow our&#xD;
      instructions about how to take the study drug. Participants can take the drug with or without&#xD;
      food. Investigators will provide enough study drug for participants to take until the next&#xD;
      visit.&#xD;
&#xD;
      For this study, there are 3 blocks: each month-long block will consist of MPH for a two-week&#xD;
      period (I.e. &quot;A&quot; Blocks 1, 2, 3) and PBO for a two-week period (I.e. &quot;B&quot; Blocks 1, 2, 3) in&#xD;
      random assignment order for each block. Thus, all volunteers will receive a four-week&#xD;
      PBO-lead in and acclimatization followed by treatment with MPH or matching PBO for&#xD;
      eight-weeks each in three randomized sequence crossover blocks for a total of 10 weeks of PBO&#xD;
      and 6 weeks of MPH.&#xD;
&#xD;
      Weekly Tasks During the study, certain tasks must be done each week.&#xD;
&#xD;
      Every Day:&#xD;
&#xD;
      The following tasks must be done each day throughout the study:&#xD;
&#xD;
        -  Wear the activity tracker&#xD;
&#xD;
        -  Take study medication&#xD;
&#xD;
      Six Days per Week:&#xD;
&#xD;
      The following tasks will be completed six days per week:&#xD;
&#xD;
        -  Complete online cognitive games&#xD;
&#xD;
           o Use online brain games to rate daily mood and sleep quality&#xD;
&#xD;
        -  Synchronize Fitness tracker to study provided tablet (if requested)&#xD;
&#xD;
      Once every five days:&#xD;
&#xD;
      The following activities must be done approximately every five days throughout the trial:&#xD;
&#xD;
      • Charge Fitness tracker during a time when the subject is resting but not sleeping&#xD;
&#xD;
      The study coordinator will periodically log into both the Fitness tracker dashboard and the&#xD;
      online brain game account to check the battery level of the Fitness tracker, ensure the&#xD;
      Fitness tracker is synching to the Fitness tracker dashboard, and monitor the completion of&#xD;
      cognitive exercises.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 1, 2019</start_date>
  <completion_date type="Actual">August 30, 2021</completion_date>
  <primary_completion_date type="Actual">August 30, 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>The study uses a double-blinded, multi-crossover, randomized controlled trial design. This type of trial design in AD allow for each subject to serve as their own control as they progress through several randomized blocks of experimental treatment and placebo. Thus, multi-crossover studies carried out with systemically applied outcome measures, pre-specified doses of study drug, and washout periods serve as unbiased estimates of treatment effect for individual subjects. When data from several subjects are analyzed together following such a N-of-1 design, substantial increases in statistical power is afforded with a fraction of the subjects and assessments required for similar levels of power in conventional parallel group trials. There are 6 different block randomization sequences for which subjects were assigned.</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Feasibility of a Virtual Multicrossover Randomized Control Trial Design as Measured my Completion Rates and Medication Compliance.</measure>
    <time_frame>4 months</time_frame>
    <description>To assess feasibility of this study design, completion rates of all study tasks and medication dosing will be evaluated. Benchmark goals for feasibility measures are set as follows: retain &gt;80% of participants enrolled, observe &gt;80% medication adherence, and &gt;80% outcome assessment completion rates.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cognition as Measured by the Repeatable Battery for the Assessment Neuropsychological Status-Update (RBANS)</measure>
    <time_frame>4 months</time_frame>
    <description>This study is investigating the effects of methylphenidate to see if it will help improve cognition in adults with Alzheimer's Disease. RBANS scores range from 40 to 160 with higher scores indicating higher cognitive functioning.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognition as Measured by Daily, Home-based Brain Games (Lumosity, Lumos Labs, Inc.)</measure>
    <time_frame>4 months</time_frame>
    <description>This study is investigating the effects of methylphenidate to see if it will help improve cognition in adults with Alzheimer's Disease using daily Lumosity brain games. The range of possible Lumosity scores varies, but higher scores indicate better game performance. LPI (Lumosity Performance Index) is a standardized performance metric that shows how well you are performing on Lumosity games and lets you compare performance across games and Cognitive Areas. Cognitive LPI is calculated using a weighted average of the Game LPIs from all Cognitive Areas. LPI: The low score is 0, the high score is 2000. Average is 1000.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sleep as Measured by Fitbit Charge 3</measure>
    <time_frame>4 months</time_frame>
    <description>This study is investigating whether treatment with methylphenidate affects sleep levels. Methylphenidate may increase daily activity or affect the amount or quality of sleep.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Activity Level as Measured by Fitbit During MPH/PBO Blocks</measure>
    <time_frame>4 months</time_frame>
    <description>Activity level as measured by the fitbit during MPH/Placebo blocks</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Alzheimer Dementia</condition>
  <arm_group>
    <arm_group_label>Sequence 1:MPH, PBO, MPH, PBO, PBO, MPH</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO &quot;blocks&quot;. Each &quot;block&quot; consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received Methylphenidate (MPH) for 2 weeks, then placebo for 2 weeks, then MPH for 2 weeks, then Placebo for 2 weeks, then Placebo for 2 weeks, then MPH for 2 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sequence 2:MPH, PBO, PBO, MPH, MPH, PBO</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO &quot;blocks&quot;. Each &quot;block&quot; consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received Methylphenidate (MPH) for 2 weeks, then placebo for 2 weeks, then PBO for 2 weeks, then MPH for 2 weeks, then MPH for 2 weeks, then PBO for 2 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sequence 3:MPH, PBO, PBO, MPH, PBO, MPH</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO &quot;blocks&quot;. Each &quot;block&quot; consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received Methylphenidate (MPH) for 2 weeks, then placebo for 2 weeks, then MPH for 2 weeks, then Placebo for 2 weeks, then Placebo for 2 weeks, then MPH for 2 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sequence 4:PBO, MPH, MPH, PBO, MPH, PBO</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO &quot;blocks&quot;. Each &quot;block&quot; consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received PBO for 2 weeks, then MPH for 2 weeks, then MPH for 2 weeks, then Placebo for 2 weeks, then MPH for 2 weeks, then PBO for 2 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sequence 5: PBO, MPH, MPH, PBO, PBO, MPH</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO &quot;blocks&quot;. Each &quot;block&quot; consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received PBO for 2 weeks, then MPH for 2 weeks, then MPH for 2 weeks, then Placebo for 2 weeks, then Placebo for 2 weeks, then MPH for 2 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sequence 6: PBO, MPH, PBO, MPH, MPH, PBO</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO &quot;blocks&quot;. Each &quot;block&quot; consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received PBO for 2 weeks, then MPH for 2 weeks, then PBO for 2 weeks, then MPH for 2 weeks, then MPH for 2 weeks, then PBO for 2 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methylphenidate Extended Release Oral Capsule</intervention_name>
    <description>Stimulant It can treat ADHD and narcolepsy.&#xD;
1 capsule 18mg</description>
    <arm_group_label>Sequence 1:MPH, PBO, MPH, PBO, PBO, MPH</arm_group_label>
    <arm_group_label>Sequence 2:MPH, PBO, PBO, MPH, MPH, PBO</arm_group_label>
    <arm_group_label>Sequence 3:MPH, PBO, PBO, MPH, PBO, MPH</arm_group_label>
    <arm_group_label>Sequence 4:PBO, MPH, MPH, PBO, MPH, PBO</arm_group_label>
    <arm_group_label>Sequence 5: PBO, MPH, MPH, PBO, PBO, MPH</arm_group_label>
    <arm_group_label>Sequence 6: PBO, MPH, PBO, MPH, MPH, PBO</arm_group_label>
    <other_name>Ritalin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo comparator MPH Matched Placebo Tablet</description>
    <arm_group_label>Sequence 1:MPH, PBO, MPH, PBO, PBO, MPH</arm_group_label>
    <arm_group_label>Sequence 2:MPH, PBO, PBO, MPH, MPH, PBO</arm_group_label>
    <arm_group_label>Sequence 3:MPH, PBO, PBO, MPH, PBO, MPH</arm_group_label>
    <arm_group_label>Sequence 4:PBO, MPH, MPH, PBO, MPH, PBO</arm_group_label>
    <arm_group_label>Sequence 5: PBO, MPH, MPH, PBO, PBO, MPH</arm_group_label>
    <arm_group_label>Sequence 6: PBO, MPH, PBO, MPH, MPH, PBO</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Study subjects meeting all of the following criteria will be allowed to enroll in the&#xD;
             study:&#xD;
&#xD;
               1. Aged 55-95 inclusive;&#xD;
&#xD;
               2. Diagnosis of MCI or mild-stage dementia presumed due to AD and AD-related&#xD;
                  disorders;&#xD;
&#xD;
               3. Cognitive abilities sufficient to be able to complete all study tasks as&#xD;
                  determined by the PI or a Co-I;&#xD;
&#xD;
               4. Education level, English language skills, and literacy that indicates participant&#xD;
                  will be able to comprehend all assessments;&#xD;
&#xD;
               5. Neuropsychiatric Inventory Agitation/Aggression Question 4 = &quot;No&quot; or &quot;Yes&quot; with a&#xD;
                  mild severity rating.&#xD;
&#xD;
               6. Willing and able to complete all assessments and study procedures;&#xD;
&#xD;
               7. Not pregnant, lactating, or of child-bearing potential&#xD;
&#xD;
               8. Volunteer has a Study Partner with at least two days per week of contact and&#xD;
                  willing to complete partner study forms;&#xD;
&#xD;
               9. No exclusionary medications or dietary supplements. See Section 6.5.8.1&#xD;
&#xD;
              10. If on cholinesterase inhibitor and/or memantine, doses are stable for 3 months&#xD;
                  prior to baseline.&#xD;
&#xD;
              11. Basic video conferencing capabilities and a willingness to participate in a&#xD;
                  virtual trial (including self-administration of ECG).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects meeting any of the following criteria during the screening evaluation will be&#xD;
             excluded:&#xD;
&#xD;
               1. Any history of specific CNS disease other than AD or AD-related disorders, such&#xD;
                  as major clinical stroke, brain tumor, normal pressure hydrocephalus, multiple&#xD;
                  sclerosis, significant head trauma with persistent neurological or cognitive&#xD;
                  deficits or complaints;&#xD;
&#xD;
               2. Clinically significant or unstable medical condition that could affect safety or&#xD;
                  compliance with the study and would, in the opinion of the investigator, pose a&#xD;
                  risk to the participant if they were to participate in the study;&#xD;
&#xD;
               3. Major active or chronic psychiatric illness (e.g. depression, bipolar disorder,&#xD;
                  obsessive compulsive disorder, schizophrenia) within the previous year;&#xD;
&#xD;
               4. Current suicidal ideation or history of suicide attempt;&#xD;
&#xD;
               5. History of alcohol or other substance abuse or dependence with the past two&#xD;
                  years;&#xD;
&#xD;
               6. Clinically significant abnormalities on complete blood count, comprehensive&#xD;
                  metabolic panel, B12, or TSH screening safety lab results;&#xD;
&#xD;
               7. Concomitant use of medications with psychoactive properties that may&#xD;
                  deleteriously affect cognition (anticholinergics, antihistamines, antipsychotics,&#xD;
                  sedative hypnotics, anxiolytics);&#xD;
&#xD;
               8. Treatment with monoamine oxidase inhibitors, coumadin, phenobarbital, phenytoin,&#xD;
                  primidone, tricyclic antidepressants or other medicines with potential for&#xD;
                  clinically significant interaction;&#xD;
&#xD;
               9. Hypersensitivity to MPH;&#xD;
&#xD;
              10. History of marked anxiety and agitation, ADHD, motor tics, glaucoma, or a history&#xD;
                  or family history of Tourette's Syndrome;&#xD;
&#xD;
              11. Clinically significant cardiac condition for which MPH may be contradicted as&#xD;
                  determined by study physician, such as MI or ventricular arrhythmia within 6&#xD;
                  months of enrollment;&#xD;
&#xD;
              12. History of untreated, uncontrolled hypertension or a blood pressure greater than&#xD;
                  150/90 during the screening period;&#xD;
&#xD;
              13. Use of other small molecule or device- based investigational agents one month&#xD;
                  prior to entry and for the duration of the trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>95 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steven E Arnold, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>MGH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts General Hospital, Clinical Translational Research Unit</name>
      <address>
        <city>Charlestown</city>
        <state>Massachusetts</state>
        <zip>02129</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 17, 2019</study_first_submitted>
  <study_first_submitted_qc>January 18, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 22, 2019</study_first_posted>
  <results_first_submitted>December 19, 2022</results_first_submitted>
  <results_first_submitted_qc>June 1, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">June 2, 2023</results_first_posted>
  <last_update_submitted>June 1, 2023</last_update_submitted>
  <last_update_submitted_qc>June 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Steven E Arnold, MD</investigator_full_name>
    <investigator_title>Managing Director Physician</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dementia</mesh_term>
    <mesh_term>Alzheimer Disease</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methylphenidate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 23, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/47/NCT03811847/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>11 Participants signed consent and enrolled. 3 Screen failed and 1 Withdrew due to study non compliance, prior to assignment to groups. 7 participants proceeded to assignment and Block 1A.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Experimental: Sequence 1:MPH, PBO, MPH, PBO, PBO, MPH</title>
          <description>Experimental: Sequence 1:MPH, PBO, MPH, PBO, PBO, MPH&#xD;
Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO &quot;blocks&quot;. Each &quot;block&quot; consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received Methylphenidate (MPH) for 2 weeks, then placebo for 2 weeks, then MPH for 2 weeks, then Placebo for 2 weeks, then Placebo for 2 weeks, then MPH for 2 weeks.</description>
        </group>
        <group group_id="P2">
          <title>Experimental: Sequence 2:MPH, PBO, PBO, MPH, MPH, PBO</title>
          <description>Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO &quot;blocks&quot;. Each &quot;block&quot; consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received Methylphenidate (MPH) for 2 weeks, then placebo for 2 weeks, then PBO for 2 weeks, then MPH for 2 weeks, then MPH for 2 weeks, then PBO for 2 weeks.</description>
        </group>
        <group group_id="P3">
          <title>Experimental: Sequence 3:MPH, PBO, PBO, MPH, PBO, MPH</title>
          <description>Experimental: Sequence 3:MPH, PBO, PBO, MPH, PBO, MPH Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO &quot;blocks&quot;. Each &quot;block&quot; consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received Methylphenidate (MPH) for 2 weeks, then placebo for 2 weeks, then MPH for 2 weeks, then Placebo for 2 weeks, then Placebo for 2 weeks, then MPH for 2 weeks.</description>
        </group>
        <group group_id="P4">
          <title>Experimental: Sequence 4:PBO, MPH, MPH, PBO, MPH, PBO</title>
          <description>Experimental: Sequence 4:PBO, MPH, MPH, PBO, MPH, PBO Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO &quot;blocks&quot;. Each &quot;block&quot; consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received PBO for 2 weeks, then MPH for 2 weeks, then MPH for 2 weeks, then Placebo for 2 weeks, then MPH for 2 weeks, then PBO for 2 weeks.</description>
        </group>
        <group group_id="P5">
          <title>Experimental: Sequence 5: PBO, MPH, MPH, PBO, PBO, MPH</title>
          <description>Experimental: Sequence 5: PBO, MPH, MPH, PBO, PBO, MPH Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO &quot;blocks&quot;. Each &quot;block&quot; consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received PBO for 2 weeks, then MPH for 2 weeks, then MPH for 2 weeks, then Placebo for 2 weeks, then Placebo for 2 weeks, then MPH for 2 weeks.</description>
        </group>
        <group group_id="P6">
          <title>Experimental: Sequence 6: PBO, MPH, PBO, MPH, MPH, PBO</title>
          <description>Experimental: Sequence 6: PBO, MPH, PBO, MPH, MPH, PBO Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO &quot;blocks&quot;. Each &quot;block&quot; consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received PBO for 2 weeks, then MPH for 2 weeks, then PBO for 2 weeks, then MPH for 2 weeks, then MPH for 2 weeks, then PBO for 2 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Block 1A</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Block 1B</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Block 2 A</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Block 2B</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Block 3A</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Block 3B</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Participants were analyzed in treatment/placebo groups based on randomized crossover assignment.</population>
      <group_list>
        <group group_id="B1">
          <title>Randomized Crossover Methylphenidate/Placebo</title>
          <description>During this study, participants will get both the study drug Methylphenidate Extended Release Capsule and the placebo in random order. Placebo is being used in this study to compare to see if any improvements in cognition other areas are due to the study drug or due to other reasons.&#xD;
Methylphenidate Extended Release Oral Capsule: Stimulant It can treat ADHD and narcolepsy.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="7"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="63.57" spread="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Feasibility of a Virtual Multicrossover Randomized Control Trial Design as Measured my Completion Rates and Medication Compliance.</title>
        <description>To assess feasibility of this study design, completion rates of all study tasks and medication dosing will be evaluated. Benchmark goals for feasibility measures are set as follows: retain &gt;80% of participants enrolled, observe &gt;80% medication adherence, and &gt;80% outcome assessment completion rates.</description>
        <time_frame>4 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>All Study Participants</title>
            <description>During this study, participants will get both the study drug Methylphenidate Extended Release Capsule and the placebo in random order.&#xD;
For this study, there are 3 blocks: each month-long block will consist of MPH for a two-week period (I.e. Blocks 1a, 2a, 3a) and PBO for a two-week period (I.e. Blocks 1b, 2b, 3b) in random assignment order for each block. Thus, all volunteers will receive a four-week PBO-lead in and acclimatization followed by treatment with MPH or matching PBO for eight-weeks each in three randomized sequence crossover blocks for a total of 10 weeks of PBO and 6 weeks of MPH.</description>
          </group>
        </group_list>
        <measure>
          <title>Feasibility of a Virtual Multicrossover Randomized Control Trial Design as Measured my Completion Rates and Medication Compliance.</title>
          <description>To assess feasibility of this study design, completion rates of all study tasks and medication dosing will be evaluated. Benchmark goals for feasibility measures are set as follows: retain &gt;80% of participants enrolled, observe &gt;80% medication adherence, and &gt;80% outcome assessment completion rates.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participant retention</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Medication Compliance</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Assessment completion</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cognition as Measured by the Repeatable Battery for the Assessment Neuropsychological Status-Update (RBANS)</title>
        <description>This study is investigating the effects of methylphenidate to see if it will help improve cognition in adults with Alzheimer's Disease. RBANS scores range from 40 to 160 with higher scores indicating higher cognitive functioning.</description>
        <time_frame>4 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Study Participants on MPH Treatment</title>
            <description>Study Participants on MPH Treatment Blocks</description>
          </group>
          <group group_id="O2">
            <title>Study Participants on PBO Block</title>
            <description>Study Participants on Placebo Blocks</description>
          </group>
        </group_list>
        <measure>
          <title>Cognition as Measured by the Repeatable Battery for the Assessment Neuropsychological Status-Update (RBANS)</title>
          <description>This study is investigating the effects of methylphenidate to see if it will help improve cognition in adults with Alzheimer's Disease. RBANS scores range from 40 to 160 with higher scores indicating higher cognitive functioning.</description>
          <units>scores on scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.8" spread="14.1"/>
                    <measurement group_id="O2" value="70.7" spread="13.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cognition as Measured by Daily, Home-based Brain Games (Lumosity, Lumos Labs, Inc.)</title>
        <description>This study is investigating the effects of methylphenidate to see if it will help improve cognition in adults with Alzheimer's Disease using daily Lumosity brain games. The range of possible Lumosity scores varies, but higher scores indicate better game performance. LPI (Lumosity Performance Index) is a standardized performance metric that shows how well you are performing on Lumosity games and lets you compare performance across games and Cognitive Areas. Cognitive LPI is calculated using a weighted average of the Game LPIs from all Cognitive Areas. LPI: The low score is 0, the high score is 2000. Average is 1000.</description>
        <time_frame>4 months</time_frame>
        <population>6 participants played Lumosity games. LPI values for all 12 games were averaged into an LPI Composite Score for each participant in each treatment phase (MPH or PBO) in each block (1,2,3), then averaged the LPI composites for each treatment condition (MPH or PBO) for each individual, and then averaged the individuals for each treatment condition and got the standard deviation.</population>
        <group_list>
          <group group_id="O1">
            <title>Study Participants on MPH Blocks</title>
            <description>Study Participants on MPH Treatment Blocks</description>
          </group>
          <group group_id="O2">
            <title>Study Participants on Placebo</title>
            <description>Study Participants on PBO Blocks</description>
          </group>
        </group_list>
        <measure>
          <title>Cognition as Measured by Daily, Home-based Brain Games (Lumosity, Lumos Labs, Inc.)</title>
          <description>This study is investigating the effects of methylphenidate to see if it will help improve cognition in adults with Alzheimer's Disease using daily Lumosity brain games. The range of possible Lumosity scores varies, but higher scores indicate better game performance. LPI (Lumosity Performance Index) is a standardized performance metric that shows how well you are performing on Lumosity games and lets you compare performance across games and Cognitive Areas. Cognitive LPI is calculated using a weighted average of the Game LPIs from all Cognitive Areas. LPI: The low score is 0, the high score is 2000. Average is 1000.</description>
          <population>6 participants played Lumosity games. LPI values for all 12 games were averaged into an LPI Composite Score for each participant in each treatment phase (MPH or PBO) in each block (1,2,3), then averaged the LPI composites for each treatment condition (MPH or PBO) for each individual, and then averaged the individuals for each treatment condition and got the standard deviation.</population>
          <units>scores on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="465.8" spread="308.4"/>
                    <measurement group_id="O2" value="451.6" spread="291.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Sleep as Measured by Fitbit Charge 3</title>
        <description>This study is investigating whether treatment with methylphenidate affects sleep levels. Methylphenidate may increase daily activity or affect the amount or quality of sleep.</description>
        <time_frame>4 months</time_frame>
        <population>Data was not collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Participants on MPH Block</title>
            <description>Fit bit Data from participants while on Methylphenidate treatment block</description>
          </group>
          <group group_id="O2">
            <title>Participants on PBO Block</title>
            <description>Fit bit Data from participants while on PBO treatment block</description>
          </group>
        </group_list>
        <measure>
          <title>Sleep as Measured by Fitbit Charge 3</title>
          <description>This study is investigating whether treatment with methylphenidate affects sleep levels. Methylphenidate may increase daily activity or affect the amount or quality of sleep.</description>
          <population>Data was not collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Activity Level as Measured by Fitbit During MPH/PBO Blocks</title>
        <description>Activity level as measured by the fitbit during MPH/Placebo blocks</description>
        <time_frame>4 months</time_frame>
        <population>Data was not collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Activity While Participants on MPH Treatment Block</title>
            <description>Fit bit Data from participants while on Methylphenidate treatment block</description>
          </group>
          <group group_id="O2">
            <title>Activity While Participants on Placebo Block</title>
            <description>Fit bit Data from participants while on PBO treatment block</description>
          </group>
        </group_list>
        <measure>
          <title>Activity Level as Measured by Fitbit During MPH/PBO Blocks</title>
          <description>Activity level as measured by the fitbit during MPH/Placebo blocks</description>
          <population>Data was not collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data was collected from each participant up to 18 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>AEs While Participants on MPH Treatment Block</title>
          <description>AEs that occurred while participants were on Methylphenidate treatment block</description>
        </group>
        <group group_id="E2">
          <title>AEs While Participants on Placebo Block</title>
          <description>AEs that occurred while participants were on Placebo block</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>diarrhea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>insomnia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>anxiety</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Steven Arnold, MD</name_or_title>
      <organization>Massachusetts General Hospital</organization>
      <phone>617-643-5607</phone>
      <email>searnold@mgh.harvard.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03811847
org study id: 2018P003099
nct id: NCT03811847
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Investigators are doing this research study to find out if methylphenidate (MPH) can help
      people with Mild Cognitive Impairment (MCI) or mild dementia likely due to Alzheimer's
      Disease (AD) and related disorders (ADRD).

      The study drug MPH is approved by the U.S. Food and Drug Administration (FDA) to treat
      Attention Deficit/Hyperactivity Disorder (ADHD), but MPH is not approved by the FDA to treat
      Mild Cognitive Impairment or mild dementia related to Alzheimer's Disease. However, other
      studies have been done in which MPH has been given to people with neurodegenerative dementias
      and results have shown some improvement in these people's mood and cognition. Investigators
      would like to see if MPH will help mood and cognition.

      This study will take place completely virtually (with the option to come in for the first
      visit to meet the study team). All study visits will occur over a secure videoconferencing
      platform. All study materials will be shipped directly to the home of each participant.
Investigators will give participants a supply of study drug. Participants will take the study
      drug by mouth once a day for 16 weeks. It is important for participants to follow our
      instructions about how to take the study drug. Participants can take the drug with or without
      food. Investigators will provide enough study drug for participants to take until the next
      visit.

      For this study, there are 3 blocks: each month-long block will consist of MPH for a two-week
      period (I.e. "A" Blocks 1, 2, 3) and PBO for a two-week period (I.e. "B" Blocks 1, 2, 3) in
      random assignment order for each block. Thus, all volunteers will receive a four-week
      PBO-lead in and acclimatization followed by treatment with MPH or matching PBO for
      eight-weeks each in three randomized sequence crossover blocks for a total of 10 weeks of PBO
      and 6 weeks of MPH.

      Weekly Tasks During the study, certain tasks must be done each week.

      Every Day:

      The following tasks must be done each day throughout the study:

        -  Wear the activity tracker

        -  Take study medication

      Six Days per Week:

      The following tasks will be completed six days per week:

        -  Complete online cognitive games

           o Use online brain games to rate daily mood and sleep quality

        -  Synchronize Fitness tracker to study provided tablet (if requested)

      Once every five days:

      The following activities must be done approximately every five days throughout the trial:

      • Charge Fitness tracker during a time when the subject is resting but not sleeping

      The study coordinator will periodically log into both the Fitness tracker dashboard and the
      online brain game account to check the battery level of the Fitness tracker, ensure the
      Fitness tracker is synching to the Fitness tracker dashboard, and monitor the completion of
      cognitive exercises.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: The study uses a double-blinded, multi-crossover, randomized controlled trial design. This type of trial design in AD allow for each subject to serve as their own control as they progress through several randomized blocks of experimental treatment and placebo. Thus, multi-crossover studies carried out with systemically applied outcome measures, pre-specified doses of study drug, and washout periods serve as unbiased estimates of treatment effect for individual subjects. When data from several subjects are analyzed together following such a N-of-1 design, substantial increases in statistical power is afforded with a fraction of the subjects and assessments required for similar levels of power in conventional parallel group trials. There are 6 different block randomization sequences for which subjects were assigned.
primary purpose: Supportive Care
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Feasibility of a Virtual Multicrossover Randomized Control Trial Design as Measured my Completion Rates and Medication Compliance.
time frame: 4 months
description: To assess feasibility of this study design, completion rates of all study tasks and medication dosing will be evaluated. Benchmark goals for feasibility measures are set as follows: retain >80% of participants enrolled, observe >80% medication adherence, and >80% outcome assessment completion rates.
measure: Cognition as Measured by the Repeatable Battery for the Assessment Neuropsychological Status-Update (RBANS)
time frame: 4 months
description: This study is investigating the effects of methylphenidate to see if it will help improve cognition in adults with Alzheimer's Disease. RBANS scores range from 40 to 160 with higher scores indicating higher cognitive functioning.
measure: Cognition as Measured by Daily, Home-based Brain Games (Lumosity, Lumos Labs, Inc.)
time frame: 4 months
description: This study is investigating the effects of methylphenidate to see if it will help improve cognition in adults with Alzheimer's Disease using daily Lumosity brain games. The range of possible Lumosity scores varies, but higher scores indicate better game performance. LPI (Lumosity Performance Index) is a standardized performance metric that shows how well you are performing on Lumosity games and lets you compare performance across games and Cognitive Areas. Cognitive LPI is calculated using a weighted average of the Game LPIs from all Cognitive Areas. LPI: The low score is 0, the high score is 2000. Average is 1000.
measure: Sleep as Measured by Fitbit Charge 3
time frame: 4 months
description: This study is investigating whether treatment with methylphenidate affects sleep levels. Methylphenidate may increase daily activity or affect the amount or quality of sleep.
measure: Activity Level as Measured by Fitbit During MPH/PBO Blocks
time frame: 4 months
description: Activity level as measured by the fitbit during MPH/Placebo blocks
arm group label: Sequence 1:MPH, PBO, MPH, PBO, PBO, MPH
arm group type: Experimental
description: Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO "blocks". Each "block" consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received Methylphenidate (MPH) for 2 weeks, then placebo for 2 weeks, then MPH for 2 weeks, then Placebo for 2 weeks, then Placebo for 2 weeks, then MPH for 2 weeks.
arm group label: Sequence 2:MPH, PBO, PBO, MPH, MPH, PBO
arm group type: Experimental
description: Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO "blocks". Each "block" consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received Methylphenidate (MPH) for 2 weeks, then placebo for 2 weeks, then PBO for 2 weeks, then MPH for 2 weeks, then MPH for 2 weeks, then PBO for 2 weeks.
arm group label: Sequence 3:MPH, PBO, PBO, MPH, PBO, MPH
arm group type: Experimental
description: Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO "blocks". Each "block" consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received Methylphenidate (MPH) for 2 weeks, then placebo for 2 weeks, then MPH for 2 weeks, then Placebo for 2 weeks, then Placebo for 2 weeks, then MPH for 2 weeks.
arm group label: Sequence 4:PBO, MPH, MPH, PBO, MPH, PBO
arm group type: Experimental
description: Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO "blocks". Each "block" consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received PBO for 2 weeks, then MPH for 2 weeks, then MPH for 2 weeks, then Placebo for 2 weeks, then MPH for 2 weeks, then PBO for 2 weeks.
arm group label: Sequence 5: PBO, MPH, MPH, PBO, PBO, MPH
arm group type: Experimental
description: Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO "blocks". Each "block" consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received PBO for 2 weeks, then MPH for 2 weeks, then MPH for 2 weeks, then Placebo for 2 weeks, then Placebo for 2 weeks, then MPH for 2 weeks.
arm group label: Sequence 6: PBO, MPH, PBO, MPH, MPH, PBO
arm group type: Experimental
description: Over the 16-week study, each participant moved through four, 4-week treatment periods: a Placebo (PBO) lead-in, acclimation period followed by three, crossover Methylphenidate (MPH) vs PBO "blocks". Each "block" consisted of treatment with MPH for two-weeks and treatment with PBO for two-weeks; each block order will be randomly assigned. In this group, participants first received PBO for 2 weeks, then MPH for 2 weeks, then PBO for 2 weeks, then MPH for 2 weeks, then MPH for 2 weeks, then PBO for 2 weeks.
intervention type: Drug
intervention name: Methylphenidate Extended Release Oral Capsule
description: Stimulant It can treat ADHD and narcolepsy.
1 capsule 18mg
arm group label: Sequence 1:MPH, PBO, MPH, PBO, PBO, MPH
arm group label: Sequence 2:MPH, PBO, PBO, MPH, MPH, PBO
arm group label: Sequence 3:MPH, PBO, PBO, MPH, PBO, MPH
arm group label: Sequence 4:PBO, MPH, MPH, PBO, MPH, PBO
arm group label: Sequence 5: PBO, MPH, MPH, PBO, PBO, MPH
arm group label: Sequence 6: PBO, MPH, PBO, MPH, MPH, PBO
other name: Ritalin
intervention type: Other
intervention name: Placebo
description: Placebo comparator MPH Matched Placebo Tablet
arm group label: Sequence 1:MPH, PBO, MPH, PBO, PBO, MPH
arm group label: Sequence 2:MPH, PBO, PBO, MPH, MPH, PBO
arm group label: Sequence 3:MPH, PBO, PBO, MPH, PBO, MPH
arm group label: Sequence 4:PBO, MPH, MPH, PBO, MPH, PBO
arm group label: Sequence 5: PBO, MPH, MPH, PBO, PBO, MPH
arm group label: Sequence 6: PBO, MPH, PBO, MPH, MPH, PBO
criteria: 
gender: All
minimum age: 55 Years
maximum age: 95 Years
healthy volunteers: No
last name: Steven E Arnold, MD
role: Principal Investigator
affiliation: MGH
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Steven E Arnold, MD
investigator title: Managing Director Physician
mesh term: Dementia
mesh term: Alzheimer Disease
mesh term: Cognitive Dysfunction
mesh term: Methylphenidate
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 