<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/NCT03784183</url>
  </required_header>
  <id_info>
    <org_study_id>BSP-2018</org_study_id>
    <nct_id>NCT03784183</nct_id>
  </id_info>
  <brief_title>Neuropsychological and Neurophysiological Effects of Cognitive Stimulation in Patients With Alzheimer's Disease and Mild Cognitive Impairment</brief_title>
  <official_title>A Randomized, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy of a Non-Pharmacological Intervention of Cognitive Stimulation in Subjects With Alzheimer's Disease and Mild Cognitive Impairment: The Brain Stimulation Project.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Roma La Sapienza</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Roma La Sapienza</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The present study aims to evaluate the effect of cognitive stimulation (CS) in participants&#xD;
      with a diagnosis of moderate and mild Alzheimer's disease (AD) and mild cognitive impairment&#xD;
      (MCI) compared to control subjects not receiving any non-pharmacological interventions.&#xD;
      Treated participants will receive a structured CS consisting of a wide range of activities&#xD;
      aimed at the general improvement of social functioning and the maintenance of cognitive&#xD;
      functions. The study consists of a 24-week treatment phase and a follow-up period of 24&#xD;
      weeks. During the treatment period, patients will receive two CS sessions a week. At&#xD;
      baseline, all the participants undergo an extensive neuropsychological evaluation and a&#xD;
      neurophysiological assessment aimed at studying the frequency of spontaneous blinking (blink&#xD;
      rate) and cortical excitability and synaptic plasticity by means of the transcranial magnetic&#xD;
      stimulation (TMS). Neuropsychological and neurophysiological evaluations will be repeated at&#xD;
      the end of the treatment (week 24) and at the end of the follow-up period (week 48) in order&#xD;
      to evaluate short- and long-term effects of CS. The hypothesis of this research is that CS&#xD;
      may improve cognition and the neurophysiological parameters studied in treated participants&#xD;
      compared to those untreated.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">September 27, 2018</start_date>
  <completion_date type="Anticipated">October 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>A Randomized, Single-Blind, Placebo-Controlled, Parallel-Group</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Single Blind: Neuropsychologists and Neurophysiologists are prevented from having knowledge of the intervention assigned to the participants.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in global cognition as assessed by Mini Mental State Examination</measure>
    <time_frame>24 and 48 weeks</time_frame>
    <description>Change from baseline in Mini Mental State Examination score at Week 24 and 48. This scale investigates global cognition. Scale range: 0-30. Normal values &gt;24. Higher values represent a better outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in dementia severity as assessed by Clinical Dementia Rating Scale</measure>
    <time_frame>24 and 48 weeks</time_frame>
    <description>Change from baseline in Clinical Dementia Rating Scale score at Week 24 and 48. This scale investigates global cognition and dementia severity. Scale range: 0-5. Normal values = 0. Higher values represent a worse outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in frontal functions as assessed by Frontal Assessment Battery</measure>
    <time_frame>24 and 48 weeks</time_frame>
    <description>Change from baseline in Frontal Assessment Battery scores at Week 24 and 48. This scale investigates the executive functions. Scale range: 0-30. Normal values ≥ 13.5. Higher values represent a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in verbal memory as assessed by Rey Auditory Verbal Learning Test</measure>
    <time_frame>24 and 48 weeks</time_frame>
    <description>Change from baseline in Rey Auditory Verbal Learning Test scores at Week 24 and 48. This test investigates verbal learning and memory. Immediate recall scale range: 0-75. Normal values &gt;28.52. Delayed recall scale range: 0-15. Normal values &gt;4.68. Higher values represent a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in attention as assessed by Visual Search Test</measure>
    <time_frame>24 and 48 weeks</time_frame>
    <description>Change from baseline in Visual Search test score at Week 24 and 48. This test investigates selective attention. Scale range: 0-60. Normal values &gt;30. Higher values represent a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in visuospatial functions as assessed by Clock Drawing Test</measure>
    <time_frame>24 and 48 weeks</time_frame>
    <description>Change from baseline in Clock Drawing Test score at Week 24 and 48. This test investigates visuospatial abilities and executive functioning. Scale range: 0-61. Normal values &gt;42.17. Higher values represent a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in naming as assessed by Boston Naming Test</measure>
    <time_frame>24 and 48 weeks</time_frame>
    <description>Change from baseline in Boston Naming test score at Week 24 and 48. This test measure object naming from line drawings. Scale range: 0-60. Normal values &gt;24. Higher values represent a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in synaptic plasticity as assessed by Paired Associative Stimulation</measure>
    <time_frame>24 and 48 weeks</time_frame>
    <description>Change from baseline in Paired Associative Stimulation at Week 24 and 48. Paired associative stimulation is a paradigm combining peripheral nerve stimulation and transcranial magnetic stimulation over the contralateral primary motor cortex. In healthy humans, Paired Associative Stimulation after-effects last about 30-60 minutes. The extent of facilitatory-Paired Associative Stimulation-induced effects on MEP amplitude ranges from 120% to 160%, while inhibitory-Paired Associative Stimulation may induce a reduction of muscle-evoked potential amplitude that ranges from 60% to 90%.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in blinking as assessed by Blink Rate Evaluation</measure>
    <time_frame>24 and 48 weeks</time_frame>
    <description>Change from baseline in the blink rate at Week 24 and 48. Spontaneous blinking was measured by the Blink Rate and was expressed as number of blinks per minute. Normal values: mean Blink Reflex value at rest is 17 blinks/minute; during conversation is 26 blinks/minute; during reading is 4.5 blinks/minute. Cut offs: not applicable.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">126</enrollment>
  <condition>Alzheimer Disease</condition>
  <arm_group>
    <arm_group_label>moderate AD-experimental</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental Intervention: The CS shall be carried out in groups (5-7 participants), twice a week. Each session lasts 90 minutes. CS sessions begin with a training for temporal and spatial orientation in which participants are asked to recognize and recall the date and the place with the help of some environmental aids (calendars, clocks, pictures and maps). Then the participants complete an array of cognitive tasks for memory, attention, language, visuo-spatial functions and executive functions. These tasks range from individual paper-and-pencil exercises to verbal-learning exercises that have to be solved by the group.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>mild AD-experimental</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental Intervention: the same of the &quot;moderate AD-experimental&quot; arm</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MCI-experimental</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental Intervention: the same of the &quot;moderate AD-experimental&quot; arm</description>
  </arm_group>
  <arm_group>
    <arm_group_label>moderate AD-placebo</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>mild AD-placebo</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>MCI-placebo</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cognitive Stimulation (CS)</intervention_name>
    <description>CS consists of a wide range of structured activities aimed at the general improvement of social functioning and the maintenance of different cognitive functions. It is a non-specific in-group approach that places particular emphasis on social interactions.</description>
    <arm_group_label>MCI-experimental</arm_group_label>
    <arm_group_label>mild AD-experimental</arm_group_label>
    <arm_group_label>moderate AD-experimental</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. moderate AD participants&#xD;
&#xD;
               -  Clinical diagnosis of probable AD (National Institute on Aging and Alzheimer's&#xD;
                  Association criteria)&#xD;
&#xD;
               -  1 &lt; Clinical Dementia Rating Scale &lt; 3&#xD;
&#xD;
               -  13 ≤ Mini-Mental State Examination &lt; 20/30&#xD;
&#xD;
               -  Modified Hachinski Ischaemic Scale (MHIS) ≤ 4&#xD;
&#xD;
               -  Geriatric Depression Scale (GDS) ≤ 6&#xD;
&#xD;
          2. mild AD participants&#xD;
&#xD;
               -  Clinical diagnosis of probable AD (National Institute on Aging and Alzheimer's&#xD;
                  Association criteria)&#xD;
&#xD;
               -  Clinical Dementia Rating Scale = 1 (memory box score ≥ 0.5)&#xD;
&#xD;
               -  20 &gt; Mini-Mental State Examination &lt; 27/30&#xD;
&#xD;
               -  Modified Hachinski Ischaemic Scale (MHIS) ≤ 4&#xD;
&#xD;
               -  Geriatric Depression Scale (GDS) ≤ 6&#xD;
&#xD;
          3. MCI participants&#xD;
&#xD;
               -  Clinical diagnosis of probable AD (National Institute on Aging and Alzheimer's&#xD;
                  Association criteria)&#xD;
&#xD;
               -  Clinical Dementia Rating Scale &lt; 1 (memory box score ≥ 0.5)&#xD;
&#xD;
               -  Mini-Mental State Examination ≥ 24/30&#xD;
&#xD;
               -  Modified Hachinski Ischaemic Scale (MHIS) ≤ 4&#xD;
&#xD;
               -  Geriatric Depression Scale (GDS) ≤ 6&#xD;
&#xD;
        Exclusion Criteria for all the participants (moderate AD, mild AD and MCI):&#xD;
&#xD;
          -  Any medical or neurological condition (other than AD) that, in the opinion of the&#xD;
             Investigator, might be a contributing cause of the subject's cognitive impairment.&#xD;
&#xD;
          -  Clinically significant psychiatric illness (e.g., uncontrolled major depression,&#xD;
             bipolar affective disorder) within 6 months prior to the enrolment.&#xD;
&#xD;
          -  Any medications that, in the opinion of the Investigator, may contribute to cognitive&#xD;
             impairment or impair the subject's ability to perform cognitive testing or complete&#xD;
             study procedures.&#xD;
&#xD;
          -  Contraindications to Transcranial Magnetic Stimulation (history of epilepsy or&#xD;
             seizures/presence of pacemaker).&#xD;
&#xD;
          -  Subject currently living in an organized care facility with extensive intervention&#xD;
             and/or support of daily living activities.&#xD;
&#xD;
          -  Inability to comply with study requirements and commitments&#xD;
&#xD;
          -  Has not one informant/care partner who, in the Investigator's opinion, has frequent&#xD;
             and sufficient contact with the subject as to be able to provide accurate information&#xD;
             about the subject's cognitive and functional abilities.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Department of Human Neuroscience, Sapienza University of Rome</name>
      <address>
        <city>Rome</city>
        <zip>00185</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carlo de Lena, MD</last_name>
      <phone>0649914028</phone>
      <phone_ext>0039</phone_ext>
      <email>carlo.delena@uniroma1.it</email>
    </contact>
    <contact_backup>
      <last_name>Alessandro Trebbastoni, MD, PhD</last_name>
      <phone>3491496146</phone>
      <phone_ext>0039</phone_ext>
      <email>alessandro.trebbastoni@uniroma1.it</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 26, 2018</study_first_submitted>
  <study_first_submitted_qc>December 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 21, 2018</study_first_posted>
  <last_update_submitted>December 20, 2018</last_update_submitted>
  <last_update_submitted_qc>December 20, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 21, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Roma La Sapienza</investigator_affiliation>
    <investigator_full_name>Carlo de Lena</investigator_full_name>
    <investigator_title>Department of Human Neuroscience</investigator_title>
  </responsible_party>
  <keyword>Alzheimer's Disease</keyword>
  <keyword>Mild Cognitive Stimulation</keyword>
  <keyword>Non Pharmacological Intervention</keyword>
  <keyword>Cognitive Stimulation</keyword>
  <keyword>Transcranial Magnetic Stimulation</keyword>
  <keyword>Blink Reflex</keyword>
  <keyword>Neuropsychological Evaluation</keyword>
  <keyword>Randomized Controlled Trial</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03784183
org study id: BSP-2018
nct id: NCT03784183
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The present study aims to evaluate the effect of cognitive stimulation (CS) in participants
      with a diagnosis of moderate and mild Alzheimer's disease (AD) and mild cognitive impairment
      (MCI) compared to control subjects not receiving any non-pharmacological interventions.
      Treated participants will receive a structured CS consisting of a wide range of activities
      aimed at the general improvement of social functioning and the maintenance of cognitive
      functions. The study consists of a 24-week treatment phase and a follow-up period of 24
      weeks. During the treatment period, patients will receive two CS sessions a week. At
      baseline, all the participants undergo an extensive neuropsychological evaluation and a
      neurophysiological assessment aimed at studying the frequency of spontaneous blinking (blink
      rate) and cortical excitability and synaptic plasticity by means of the transcranial magnetic
      stimulation (TMS). Neuropsychological and neurophysiological evaluations will be repeated at
      the end of the treatment (week 24) and at the end of the follow-up period (week 48) in order
      to evaluate short- and long-term effects of CS. The hypothesis of this research is that CS
      may improve cognition and the neurophysiological parameters studied in treated participants
      compared to those untreated.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: A Randomized, Single-Blind, Placebo-Controlled, Parallel-Group
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: Single Blind: Neuropsychologists and Neurophysiologists are prevented from having knowledge of the intervention assigned to the participants.
measure: Change in global cognition as assessed by Mini Mental State Examination
time frame: 24 and 48 weeks
description: Change from baseline in Mini Mental State Examination score at Week 24 and 48. This scale investigates global cognition. Scale range: 0-30. Normal values >24. Higher values represent a better outcome.
measure: Change in dementia severity as assessed by Clinical Dementia Rating Scale
time frame: 24 and 48 weeks
description: Change from baseline in Clinical Dementia Rating Scale score at Week 24 and 48. This scale investigates global cognition and dementia severity. Scale range: 0-5. Normal values = 0. Higher values represent a worse outcome.
measure: Change in frontal functions as assessed by Frontal Assessment Battery
time frame: 24 and 48 weeks
description: Change from baseline in Frontal Assessment Battery scores at Week 24 and 48. This scale investigates the executive functions. Scale range: 0-30. Normal values ≥ 13.5. Higher values represent a better outcome.
measure: Change in verbal memory as assessed by Rey Auditory Verbal Learning Test
time frame: 24 and 48 weeks
description: Change from baseline in Rey Auditory Verbal Learning Test scores at Week 24 and 48. This test investigates verbal learning and memory. Immediate recall scale range: 0-75. Normal values >28.52. Delayed recall scale range: 0-15. Normal values >4.68. Higher values represent a better outcome.
measure: Change in attention as assessed by Visual Search Test
time frame: 24 and 48 weeks
description: Change from baseline in Visual Search test score at Week 24 and 48. This test investigates selective attention. Scale range: 0-60. Normal values >30. Higher values represent a better outcome.
measure: Change in visuospatial functions as assessed by Clock Drawing Test
time frame: 24 and 48 weeks
description: Change from baseline in Clock Drawing Test score at Week 24 and 48. This test investigates visuospatial abilities and executive functioning. Scale range: 0-61. Normal values >42.17. Higher values represent a better outcome.
measure: Change in naming as assessed by Boston Naming Test
time frame: 24 and 48 weeks
description: Change from baseline in Boston Naming test score at Week 24 and 48. This test measure object naming from line drawings. Scale range: 0-60. Normal values >24. Higher values represent a better outcome.
measure: Change in synaptic plasticity as assessed by Paired Associative Stimulation
time frame: 24 and 48 weeks
description: Change from baseline in Paired Associative Stimulation at Week 24 and 48. Paired associative stimulation is a paradigm combining peripheral nerve stimulation and transcranial magnetic stimulation over the contralateral primary motor cortex. In healthy humans, Paired Associative Stimulation after-effects last about 30-60 minutes. The extent of facilitatory-Paired Associative Stimulation-induced effects on MEP amplitude ranges from 120% to 160%, while inhibitory-Paired Associative Stimulation may induce a reduction of muscle-evoked potential amplitude that ranges from 60% to 90%.
measure: Change in blinking as assessed by Blink Rate Evaluation
time frame: 24 and 48 weeks
description: Change from baseline in the blink rate at Week 24 and 48. Spontaneous blinking was measured by the Blink Rate and was expressed as number of blinks per minute. Normal values: mean Blink Reflex value at rest is 17 blinks/minute; during conversation is 26 blinks/minute; during reading is 4.5 blinks/minute. Cut offs: not applicable.
arm group label: moderate AD-experimental
arm group type: Experimental
description: Experimental Intervention: The CS shall be carried out in groups (5-7 participants), twice a week. Each session lasts 90 minutes. CS sessions begin with a training for temporal and spatial orientation in which participants are asked to recognize and recall the date and the place with the help of some environmental aids (calendars, clocks, pictures and maps). Then the participants complete an array of cognitive tasks for memory, attention, language, visuo-spatial functions and executive functions. These tasks range from individual paper-and-pencil exercises to verbal-learning exercises that have to be solved by the group.
arm group label: mild AD-experimental
arm group type: Experimental
description: Experimental Intervention: the same of the "moderate AD-experimental" arm
arm group label: MCI-experimental
arm group type: Experimental
description: Experimental Intervention: the same of the "moderate AD-experimental" arm
arm group label: moderate AD-placebo
arm group type: No Intervention
arm group label: mild AD-placebo
arm group type: No Intervention
arm group label: MCI-placebo
arm group type: No Intervention
intervention type: Other
intervention name: Cognitive Stimulation (CS)
description: CS consists of a wide range of structured activities aimed at the general improvement of social functioning and the maintenance of different cognitive functions. It is a non-specific in-group approach that places particular emphasis on social interactions.
arm group label: MCI-experimental
arm group label: mild AD-experimental
arm group label: moderate AD-experimental
criteria: 
gender: All
minimum age: 60 Years
maximum age: 85 Years
healthy volunteers: No
facility: 
status: Recruiting
contact: 
contact backup: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: University of Roma La Sapienza
investigator full name: Carlo de Lena
investigator title: Department of Human Neuroscience
mesh term: Alzheimer Disease
mesh term: Cognitive Dysfunction
sharing ipd: Undecided