<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/NCT04489017</url>
  </required_header>
  <id_info>
    <org_study_id>SPE.107</org_study_id>
    <nct_id>NCT04489017</nct_id>
  </id_info>
  <brief_title>Palmitoylethanolamide Combined With Luteoline in Frontotemporal Dementia Patients. A Randomized Controlled Trial</brief_title>
  <acronym>PEA-FTD</acronym>
  <official_title>Palmitoylethanolamide Combined With Luteoline in Frontotemporal Dementia Patients. A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>I.R.C.C.S. Fondazione Santa Lucia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>I.R.C.C.S. Fondazione Santa Lucia</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>
      Frontotemporal dementia (FTD) is a devastating neurodegenerative disorder. It is the second&#xD;
      most frequent cause of presenile neurodegenerative dementia in those less than 65 years of&#xD;
      age. Currently, there is no effective pharmacological treatment to slow down the progression&#xD;
      of FTD. Recently, it has been proposed that neuroinflammation could be involved in specific&#xD;
      forms of FTD and that novel drugs targeting neuroinflammation could potentially be useful in&#xD;
      FTD treatment. An available form of ultra-micronized PEA combined with luteoline (PEA-LUT)&#xD;
      has gained attention for its proven anti-inflammatory and neuroprotective properties reported&#xD;
      in neurodegenerative conditions related to FTD, such as Amyotrophic Lateral Sclerosis. The&#xD;
      administration of PEA-LUT treatment may have a clinical impact in behavioural variant FTD&#xD;
      (bv-FTD) patients. In particular, PEA-LUT treatment could be able to reduce behavioural&#xD;
      disturbances, the more disabling symptoms in bv-FTD, with a related improvement of daily&#xD;
      living activities of affected people. Moreover, a multimodal approach&#xD;
      (cognitive/neurophysiological) can be used to assess the brain correlates related to the&#xD;
      clinical improvement associated with PEA-LUT treatment, thus making remarkable strides in&#xD;
      understanding how FTD affects the brain. Potentially the proposed project could provide a&#xD;
      valid treatment for cognitive and behavioural dysfunction in FTD patients, with consistent&#xD;
      impact for the National Health Systems and minimum cost for the patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 1, 2019</start_date>
  <completion_date type="Anticipated">June 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2022</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>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical Dementia Rating Scale- Frontotemporal dementia Sumo of Boxes (CDR-FTD-SOB)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Battery to evaluate global disease severity</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Frontal Assessment Battery (FAB)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Battery to evaluate executive functions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Screening for aphasia in Neurodegeneration (SAND)</measure>
    <time_frame>24 weeks</time_frame>
    <description>battery to evaluate language functions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)</measure>
    <time_frame>24 weeks</time_frame>
    <description>battery to evaluate activities of daily living</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mini Mental State Examination (MMSE)</measure>
    <time_frame>24 weeks</time_frame>
    <description>battery to evaluate global cognition</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long intracortical inhibition (LICI)</measure>
    <time_frame>24 weeks</time_frame>
    <description>TMS protocol to evaluate GABA(B)ergic transmission</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sort intracortical inhibition (SICI)</measure>
    <time_frame>24 weeks</time_frame>
    <description>TMS protocol to evaluate GABA(B)ergic transmission</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TMS-EEG</measure>
    <time_frame>24 weeks</time_frame>
    <description>power in beta-gamma band to evaluate prefrontal cortical oscillatory activity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuropsychiatric Inventory (NPI)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Battery to assess behavioral changes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Addenbrooke's Cognitive Examination Revised (ACE-R)</measure>
    <time_frame>24 weeks</time_frame>
    <description>Battery to evaluate global cognition changes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frontal Behavioural Inventory</measure>
    <time_frame>24 weeks</time_frame>
    <description>Battery to evaluate behavioural functions</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Frontotemporal Dementia</condition>
  <arm_group>
    <arm_group_label>PEA-LUT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PEA-LUT administration at the oral dosage of 700 mg x 2/day for 24 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PLACEBO</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>PLACEBO administration at the oral dosage of 700 mg x 2/day for 24 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>PEA-LUT</intervention_name>
    <description>PEA-LUT administration at the oral dosage of 700 mg x 2/day</description>
    <arm_group_label>PEA-LUT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>PLACEBO</intervention_name>
    <description>PLACEBO administration at the oral dosage of 700 mg x 2/day</description>
    <arm_group_label>PLACEBO</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The patient has a diagnosis of probable Frontotemporal dementia behavioural variant&#xD;
             (bv-FTD) based on the International consensus clinical diagnostic criteria described&#xD;
             by Rascovsky et al., 2011.&#xD;
&#xD;
          2. The patient is a man or a woman, aged from 40 to 85 years.&#xD;
&#xD;
          3. The patient has a Clinical Dementia Rating-FTD (CDR-FTD) total score of ≤2 at&#xD;
             Screening.&#xD;
&#xD;
          4. The patient has not been treated with acetylcholinesterase inhibitor (AChEI), i.e.,&#xD;
             donepezil, galantamine, or rivastigmine, at the time of screening.&#xD;
&#xD;
          5. The patient is able to comply with the study procedures in the view of the&#xD;
             investigator.&#xD;
&#xD;
          6. Evidence of frontotemporal hypometabolism at PET imaging.&#xD;
&#xD;
          7. Evidence of amyloid markers excluding Alzheimer's disease (cerebrospinal fluid&#xD;
             Abeta/Tau dosages or amyloid PET imaging).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Significant neurodegenerative disorder of the central nervous system other than FTD&#xD;
             e.g., Alzheimer's disease, Lewy body dementia, Parkinson's disease, multiple&#xD;
             sclerosis, progressive supranuclear palsy, normal pressure hydrocephalus, Huntington's&#xD;
             disease, any condition directly or indirectly caused by Transmissible Spongiform&#xD;
             Encephalopathy (TSE), Creutzfeldt-Jakob Disease (CJD), variant Creutzfeldt-Jakob&#xD;
             Disease (vCJD), or new variant Creutzfeldt-Jakob Disease (nvCJD)&#xD;
&#xD;
          2. Significant intracranial focal or vascular pathology seen on brain MRI scan within a&#xD;
             maximum of 6 months before Baseline leading to a diagnosis other than probable FTD.&#xD;
&#xD;
          3. The patients has history of seizure (with the exception of febrile seizures in&#xD;
             childhood).&#xD;
&#xD;
          4. Metal implants in the head (except dental), pacemaker, cochlear implants, or any other&#xD;
             non-removable items that are contraindications to MR imaging.&#xD;
&#xD;
          5. Treatment currently or within 3 months before Baseline with any of the following&#xD;
             medications: Typical and Atypical antipsychotics (i.e., Clozapine, Olanzapine);&#xD;
             Antiepileptics drugs (i.e., Carbamazepine, Primidone, Pregabalin, Gabapentin);&#xD;
             Antidepressants (i.e., Citalopram, Duolxetine, Paroxetine).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Giacomo Koch</name>
      <address>
        <city>Rome</city>
        <zip>00179</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Giacomo Koch</last_name>
      <phone>0651501181</phone>
      <email>g.koch@hsantalucia.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Santa Lucia Foundation</name>
      <address>
        <city>Rome</city>
        <zip>00179</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sonia Bonnì</last_name>
      <phone>00390651501180</phone>
      <email>s.bonni@hsantalucia.it</email>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>April 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>January 5, 2023</last_update_submitted>
  <last_update_submitted_qc>January 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>dopamine</keyword>
  <keyword>frontal cortex</keyword>
  <keyword>GABA</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dementia</mesh_term>
    <mesh_term>Frontotemporal Dementia</mesh_term>
    <mesh_term>Aphasia, Primary Progressive</mesh_term>
    <mesh_term>Pick Disease of the Brain</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/NCT04489017
org study id: SPE.107
nct id: NCT04489017
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Frontotemporal dementia (FTD) is a devastating neurodegenerative disorder. It is the second
      most frequent cause of presenile neurodegenerative dementia in those less than 65 years of
      age. Currently, there is no effective pharmacological treatment to slow down the progression
      of FTD. Recently, it has been proposed that neuroinflammation could be involved in specific
      forms of FTD and that novel drugs targeting neuroinflammation could potentially be useful in
      FTD treatment. An available form of ultra-micronized PEA combined with luteoline (PEA-LUT)
      has gained attention for its proven anti-inflammatory and neuroprotective properties reported
      in neurodegenerative conditions related to FTD, such as Amyotrophic Lateral Sclerosis. The
      administration of PEA-LUT treatment may have a clinical impact in behavioural variant FTD
      (bv-FTD) patients. In particular, PEA-LUT treatment could be able to reduce behavioural
      disturbances, the more disabling symptoms in bv-FTD, with a related improvement of daily
      living activities of affected people. Moreover, a multimodal approach
      (cognitive/neurophysiological) can be used to assess the brain correlates related to the
      clinical improvement associated with PEA-LUT treatment, thus making remarkable strides in
      understanding how FTD affects the brain. Potentially the proposed project could provide a
      valid treatment for cognitive and behavioural dysfunction in FTD patients, with consistent
      impact for the National Health Systems and minimum cost for the patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Triple (Participant, Care Provider, Outcomes Assessor)
measure: Clinical Dementia Rating Scale- Frontotemporal dementia Sumo of Boxes (CDR-FTD-SOB)
time frame: 24 weeks
description: Battery to evaluate global disease severity
measure: Frontal Assessment Battery (FAB)
time frame: 24 weeks
description: Battery to evaluate executive functions
measure: Screening for aphasia in Neurodegeneration (SAND)
time frame: 24 weeks
description: battery to evaluate language functions
measure: Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
time frame: 24 weeks
description: battery to evaluate activities of daily living
measure: Mini Mental State Examination (MMSE)
time frame: 24 weeks
description: battery to evaluate global cognition
measure: Long intracortical inhibition (LICI)
time frame: 24 weeks
description: TMS protocol to evaluate GABA(B)ergic transmission
measure: Sort intracortical inhibition (SICI)
time frame: 24 weeks
description: TMS protocol to evaluate GABA(B)ergic transmission
measure: TMS-EEG
time frame: 24 weeks
description: power in beta-gamma band to evaluate prefrontal cortical oscillatory activity
measure: Neuropsychiatric Inventory (NPI)
time frame: 24 weeks
description: Battery to assess behavioral changes
measure: Addenbrooke's Cognitive Examination Revised (ACE-R)
time frame: 24 weeks
description: Battery to evaluate global cognition changes
measure: Frontal Behavioural Inventory
time frame: 24 weeks
description: Battery to evaluate behavioural functions
arm group label: PEA-LUT
arm group type: Experimental
description: PEA-LUT administration at the oral dosage of 700 mg x 2/day for 24 weeks
arm group label: PLACEBO
arm group type: Placebo Comparator
description: PLACEBO administration at the oral dosage of 700 mg x 2/day for 24 weeks
intervention type: Dietary Supplement
intervention name: PEA-LUT
description: PEA-LUT administration at the oral dosage of 700 mg x 2/day
arm group label: PEA-LUT
intervention type: Dietary Supplement
intervention name: PLACEBO
description: PLACEBO administration at the oral dosage of 700 mg x 2/day
arm group label: PLACEBO
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Italy
responsible party type: Sponsor
mesh term: Dementia
mesh term: Frontotemporal Dementia
mesh term: Aphasia, Primary Progressive
mesh term: Pick Disease of the Brain
sharing ipd: Undecided