<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/NCT02987842</url>
  </required_header>
  <id_info>
    <org_study_id>BeershevaMHC</org_study_id>
    <nct_id>NCT02987842</nct_id>
  </id_info>
  <brief_title>Neurofeedback as a Novel Treatment for Mild Cognitive Impairment &amp; Early Alzheimer's Disease</brief_title>
  <official_title>Neurofeedback as a Novel Treatment for Mild Cognitive Impairment &amp; Early Alzheimer's</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beersheva Mental Health Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Beersheva Mental Health Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study protocol proposes an EEG based neurofeedback (EEG-NFB) technique to upregulate the&#xD;
      posterior cingulate cortex (PCC) in patients suffering from mild cognitive impairment (MCI)&#xD;
      and early Alzheimer's disease (AD).&#xD;
&#xD;
      EEG-NFB has been successfully used as a clinical tool for over 40 years. It is based on&#xD;
      electrical activity measured near the surface of the brain using EEG and fed back to the&#xD;
      patient within half a second.&#xD;
&#xD;
      MCI is a clinical condition considered as a precursor of AD. NFB appears to be a promising&#xD;
      approach to treat MCI, since it has been shown to be able to induce changes in brain&#xD;
      plasticity. This research focuses on the PCC, which has been reported to be implicated in&#xD;
      MCI, and due to its location (proximity to the surface) accessible by means of EEG- NFB.&#xD;
&#xD;
      A preliminary research in MCI patients, conducted at our lab showed the lower the memory&#xD;
      score was at the beginning of the training, the better a subject managed to improve later on.&#xD;
      The investigators therefore presume that patients with early Alzheimer's disease, whose&#xD;
      cognitive ability is more affected compared to MCI, may benefit from EEG-NFB as well, and&#xD;
      maybe to a larger extent compared to MCI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cognitive impairment preceding dementia is called mild cognitive impairment (MCI) . Patients&#xD;
      with MCI are at high risk for progression to Alzheimer's disease (AD), at a rate of about 12%&#xD;
      per year. The amnestic form of MCI is the most common form, and most of the literature on the&#xD;
      topic refers to this form of the disorder. Clinical criteria for MCI include:&#xD;
&#xD;
        1. Memory complaint, preferably corroborated by an informant.&#xD;
&#xD;
        2. Objective memory impairment for age and education.&#xD;
&#xD;
        3. Largely intact general cognitive function.&#xD;
&#xD;
        4. Essentially preserved activities of daily living.&#xD;
&#xD;
        5. Not demented&#xD;
&#xD;
      Currently, there is no known cure for MCI or means of stopping or reversing its progression.&#xD;
      Patients with Alzheimer's disease were also included in this study , as they are considered&#xD;
      by many researchers to be on the same continuum of cognitive decline as patients with MCI&#xD;
      which indeed, carry an increased risk for developing Alzheimer's disease.&#xD;
&#xD;
      This study relies the data from a preliminary study conducted in the investigators' lab on&#xD;
      patients with MCI, and is meant to further validate our results. In the aforementioned study,&#xD;
      participants managed to improve their memory score after 10 training sessions. In addition, a&#xD;
      negative correlation between initial memory score and ability to improve was found. It is&#xD;
      therefore hypothesized that subjects with AD may benefit as much as subjects with MCI and&#xD;
      perhaps even to a larger extent.&#xD;
&#xD;
      Neurofeedback (NFB) is a treatment method based on learning with operant conditioning, in&#xD;
      which a feedback (or a reward) is given in proportion with the desired physiological activity&#xD;
      in order to improve cognition and/or behavior. This research will focus on using electrical&#xD;
      activity measured with EEG as physiological activity to be influenced.&#xD;
&#xD;
      EEG-NFB has been successfully used as a clinical tool for over 40 years treating various&#xD;
      disorders from epilepsy, attention deficit hyperactivity disorder (ADHD), stroke to PTSD&#xD;
&#xD;
      Electroencephalography (EEG) equipment is used to measure the electrical activity&#xD;
      representing the neuronal activity of different parts of the brain. During the treatment,&#xD;
      electrode(s) are placed in predetermined location. Audio and visual rewards are given when&#xD;
      the activity is measured to be within the desired frequency range.&#xD;
&#xD;
      Since NFB has been shown to be able to induce changes in the brain plasticity, it appears to&#xD;
      be a promising approach to treat MCI. Few studies have shown improvement in cognition of&#xD;
      normal elderly with subjective complains of memory decline. To the best of our knowledge,&#xD;
      this study is the first to address memory decline in MCI using EEG-based neurofeedback&#xD;
      protocol, enhancing the individual upper alpha and peak alpha frequency.&#xD;
&#xD;
      This study will include 30 participants which will be randomly assigned into experimental or&#xD;
      sham groups. The former will include training the individual upper alpha, while the latter&#xD;
      will include feedback over static electrical activity of a disconnected electrode.&#xD;
&#xD;
      each participant will be trained for a total of 10 sessions over a period of 5 weeks (2&#xD;
      training sessions per week), lasting approx. 1 hour. Cognitive evaluations will take place at&#xD;
      baseline, after the training sessions have ended and at 30 days after the last session.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>December 2016</start_date>
  <completion_date type="Anticipated">December 2017</completion_date>
  <primary_completion_date type="Anticipated">December 2017</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>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Memory performance</measure>
    <time_frame>6 weeks</time_frame>
    <description>improvement in memory performance</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>General cognitive performance improvement</measure>
    <time_frame>6 weeks</time_frame>
    <description>improvement in other cognitive domains</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>qEEG</measure>
    <time_frame>6 weeks</time_frame>
    <description>Improvement in upper alpha to lower alpha power ratio and of peak alpha frequency</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Mild Cognitive Impairment</condition>
  <condition>Alzheimer Disease</condition>
  <arm_group>
    <arm_group_label>Experimental group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients in the experimental group will receive feedback using the TruScan Neurofeedback system in order to increase the power of EEG in the range of their individual upper alpha (as determined by the peak alpha frequency)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham group</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Patients in the sham group will receive feedback using the TruScan Neurofeedback system for electrical static activity of a disconnected electrode.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>TruScan Neurofeedback</intervention_name>
    <description>Neurofeedback and quantitative EEG system</description>
    <arm_group_label>Experimental group</arm_group_label>
    <arm_group_label>Sham group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of either mild cognitive impairment or mild Alzheimer's disease&#xD;
&#xD;
          -  Age &gt; 50&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active neurological disorder&#xD;
&#xD;
          -  Any axis 1 type disorder&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Doron Todder, MD/PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beersheva Mental Health Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Doron Todder, MD/PhD</last_name>
    <phone>972-8-6401767</phone>
    <email>doron.todder@pbsh.health.gov.il</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Yotam Lavy, M.Sc</last_name>
    <phone>972-8-6401767</phone>
    <email>lavy@bgu.ac.il</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Beer-Sheva Mental Health Center</name>
      <address>
        <city>Beer-Sheva</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <reference>
    <citation>Angelakis E, Stathopoulou S, Frymiare JL, Green DL, Lubar JF, Kounios J. EEG neurofeedback: a brief overview and an example of peak alpha frequency training for cognitive enhancement in the elderly. Clin Neuropsychol. 2007 Jan;21(1):110-29. doi: 10.1080/13854040600744839.</citation>
    <PMID>17366280</PMID>
  </reference>
  <reference>
    <citation>Becerra J, Fernandez T, Roca-Stappung M, Diaz-Comas L, Galan L, Bosch J, Espino M, Moreno AJ, Harmony T. Neurofeedback in healthy elderly human subjects with electroencephalographic risk for cognitive disorder. J Alzheimers Dis. 2012;28(2):357-67. doi: 10.3233/JAD-2011-111055.</citation>
    <PMID>22002790</PMID>
  </reference>
  <reference>
    <citation>Jin G, Li K, Hu Y, Qin Y, Wang X, Xiang J, Yang Y, Lu J, Zhong N. Amnestic mild cognitive impairment: functional MR imaging study of response in posterior cingulate cortex and adjacent precuneus during problem-solving tasks. Radiology. 2011 Nov;261(2):525-33. doi: 10.1148/radiol.11102186. Epub 2011 Jul 25.</citation>
    <PMID>21788526</PMID>
  </reference>
  <reference>
    <citation>Panza F, Frisardi V, Capurso C, D'Introno A, Colacicco AM, Chiloiro R, Dellegrazie F, Di Palo A, Capurso A, Solfrizzi V. Effect of donepezil on the continuum of depressive symptoms, mild cognitive impairment, and progression to dementia. J Am Geriatr Soc. 2010 Feb;58(2):389-90. doi: 10.1111/j.1532-5415.2009.02702.x. No abstract available.</citation>
    <PMID>20370868</PMID>
  </reference>
  <reference>
    <citation>Ros T, Munneke MA, Ruge D, Gruzelier JH, Rothwell JC. Endogenous control of waking brain rhythms induces neuroplasticity in humans. Eur J Neurosci. 2010 Feb;31(4):770-8. doi: 10.1111/j.1460-9568.2010.07100.x.</citation>
    <PMID>20384819</PMID>
  </reference>
  <reference>
    <citation>Klimesch W. EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis. Brain Res Brain Res Rev. 1999 Apr;29(2-3):169-95. doi: 10.1016/s0165-0173(98)00056-3.</citation>
    <PMID>10209231</PMID>
  </reference>
  <reference>
    <citation>Jelic V, Johansson SE, Almkvist O, Shigeta M, Julin P, Nordberg A, Winblad B, Wahlund LO. Quantitative electroencephalography in mild cognitive impairment: longitudinal changes and possible prediction of Alzheimer's disease. Neurobiol Aging. 2000 Jul-Aug;21(4):533-40. doi: 10.1016/s0197-4580(00)00153-6.</citation>
    <PMID>10924766</PMID>
  </reference>
  <reference>
    <citation>Petersen RC, Caracciolo B, Brayne C, Gauthier S, Jelic V, Fratiglioni L. Mild cognitive impairment: a concept in evolution. J Intern Med. 2014 Mar;275(3):214-28. doi: 10.1111/joim.12190.</citation>
    <PMID>24605806</PMID>
  </reference>
  <reference>
    <citation>Association for Applied Psychophysiology and Biofeedback. Template for developing guidelines for the evaluation of the clinical efficacy of psychophysiological interventions. Appl Psychophysiol Biofeedback. 2002 Dec;27(4):273-81. doi: 10.1023/a:1021061318355.</citation>
    <PMID>12557455</PMID>
  </reference>
  <reference>
    <citation>Zoefel B, Huster RJ, Herrmann CS. Neurofeedback training of the upper alpha frequency band in EEG improves cognitive performance. Neuroimage. 2011 Jan 15;54(2):1427-31. doi: 10.1016/j.neuroimage.2010.08.078. Epub 2010 Sep 17.</citation>
    <PMID>20850552</PMID>
  </reference>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>December 7, 2016</study_first_submitted>
  <study_first_submitted_qc>December 8, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 9, 2016</study_first_posted>
  <last_update_submitted>December 12, 2016</last_update_submitted>
  <last_update_submitted_qc>December 12, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 13, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Beersheva Mental Health Center</investigator_affiliation>
    <investigator_full_name>Doron Todder</investigator_full_name>
    <investigator_title>Head of anxiety unit</investigator_title>
  </responsible_party>
  <keyword>Mild cognitive impairment</keyword>
  <keyword>Alzhiemer's disease</keyword>
  <keyword>Neurofeedback</keyword>
  <keyword>EEG</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>No</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/NCT02987842
org study id: BeershevaMHC
nct id: NCT02987842
lead sponsor: 
has dmc: No
This study protocol proposes an EEG based neurofeedback (EEG-NFB) technique to upregulate the
      posterior cingulate cortex (PCC) in patients suffering from mild cognitive impairment (MCI)
      and early Alzheimer's disease (AD).

      EEG-NFB has been successfully used as a clinical tool for over 40 years. It is based on
      electrical activity measured near the surface of the brain using EEG and fed back to the
      patient within half a second.

      MCI is a clinical condition considered as a precursor of AD. NFB appears to be a promising
      approach to treat MCI, since it has been shown to be able to induce changes in brain
      plasticity. This research focuses on the PCC, which has been reported to be implicated in
      MCI, and due to its location (proximity to the surface) accessible by means of EEG- NFB.

      A preliminary research in MCI patients, conducted at our lab showed the lower the memory
      score was at the beginning of the training, the better a subject managed to improve later on.
      The investigators therefore presume that patients with early Alzheimer's disease, whose
      cognitive ability is more affected compared to MCI, may benefit from EEG-NFB as well, and
      maybe to a larger extent compared to MCI.
Cognitive impairment preceding dementia is called mild cognitive impairment (MCI) . Patients
      with MCI are at high risk for progression to Alzheimer's disease (AD), at a rate of about 12%
      per year. The amnestic form of MCI is the most common form, and most of the literature on the
      topic refers to this form of the disorder. Clinical criteria for MCI include:

        1. Memory complaint, preferably corroborated by an informant.

        2. Objective memory impairment for age and education.

        3. Largely intact general cognitive function.

        4. Essentially preserved activities of daily living.

        5. Not demented

      Currently, there is no known cure for MCI or means of stopping or reversing its progression.
      Patients with Alzheimer's disease were also included in this study , as they are considered
      by many researchers to be on the same continuum of cognitive decline as patients with MCI
      which indeed, carry an increased risk for developing Alzheimer's disease.

      This study relies the data from a preliminary study conducted in the investigators' lab on
      patients with MCI, and is meant to further validate our results. In the aforementioned study,
      participants managed to improve their memory score after 10 training sessions. In addition, a
      negative correlation between initial memory score and ability to improve was found. It is
      therefore hypothesized that subjects with AD may benefit as much as subjects with MCI and
      perhaps even to a larger extent.

      Neurofeedback (NFB) is a treatment method based on learning with operant conditioning, in
      which a feedback (or a reward) is given in proportion with the desired physiological activity
      in order to improve cognition and/or behavior. This research will focus on using electrical
      activity measured with EEG as physiological activity to be influenced.

      EEG-NFB has been successfully used as a clinical tool for over 40 years treating various
      disorders from epilepsy, attention deficit hyperactivity disorder (ADHD), stroke to PTSD

      Electroencephalography (EEG) equipment is used to measure the electrical activity
      representing the neuronal activity of different parts of the brain. During the treatment,
      electrode(s) are placed in predetermined location. Audio and visual rewards are given when
      the activity is measured to be within the desired frequency range.

      Since NFB has been shown to be able to induce changes in the brain plasticity, it appears to
      be a promising approach to treat MCI. Few studies have shown improvement in cognition of
      normal elderly with subjective complains of memory decline. To the best of our knowledge,
      this study is the first to address memory decline in MCI using EEG-based neurofeedback
      protocol, enhancing the individual upper alpha and peak alpha frequency.

      This study will include 30 participants which will be randomly assigned into experimental or
      sham groups. The former will include training the individual upper alpha, while the latter
      will include feedback over static electrical activity of a disconnected electrode.

      each participant will be trained for a total of 10 sessions over a period of 5 weeks (2
      training sessions per week), lasting approx. 1 hour. Cognitive evaluations will take place at
      baseline, after the training sessions have ended and at 30 days after the last session.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Memory performance
time frame: 6 weeks
description: improvement in memory performance
measure: General cognitive performance improvement
time frame: 6 weeks
description: improvement in other cognitive domains
measure: qEEG
time frame: 6 weeks
description: Improvement in upper alpha to lower alpha power ratio and of peak alpha frequency
arm group label: Experimental group
arm group type: Experimental
description: Patients in the experimental group will receive feedback using the TruScan Neurofeedback system in order to increase the power of EEG in the range of their individual upper alpha (as determined by the peak alpha frequency)
arm group label: Sham group
arm group type: Sham Comparator
description: Patients in the sham group will receive feedback using the TruScan Neurofeedback system for electrical static activity of a disconnected electrode.
intervention type: Device
intervention name: TruScan Neurofeedback
description: Neurofeedback and quantitative EEG system
arm group label: Experimental group
arm group label: Sham group
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Doron Todder, MD/PhD
role: Principal Investigator
affiliation: Beersheva Mental Health Center
last name: Doron Todder, MD/PhD
phone: 972-8-6401767
email: doron.todder@pbsh.health.gov.il
last name: Yotam Lavy, M.Sc
phone: 972-8-6401767
email: lavy@bgu.ac.il
facility: 
country: Israel
citation: Angelakis E, Stathopoulou S, Frymiare JL, Green DL, Lubar JF, Kounios J. EEG neurofeedback: a brief overview and an example of peak alpha frequency training for cognitive enhancement in the elderly. Clin Neuropsychol. 2007 Jan;21(1):110-29. doi: 10.1080/13854040600744839.
PMID: 17366280
citation: Becerra J, Fernandez T, Roca-Stappung M, Diaz-Comas L, Galan L, Bosch J, Espino M, Moreno AJ, Harmony T. Neurofeedback in healthy elderly human subjects with electroencephalographic risk for cognitive disorder. J Alzheimers Dis. 2012;28(2):357-67. doi: 10.3233/JAD-2011-111055.
PMID: 22002790
citation: Jin G, Li K, Hu Y, Qin Y, Wang X, Xiang J, Yang Y, Lu J, Zhong N. Amnestic mild cognitive impairment: functional MR imaging study of response in posterior cingulate cortex and adjacent precuneus during problem-solving tasks. Radiology. 2011 Nov;261(2):525-33. doi: 10.1148/radiol.11102186. Epub 2011 Jul 25.
PMID: 21788526
citation: Panza F, Frisardi V, Capurso C, D'Introno A, Colacicco AM, Chiloiro R, Dellegrazie F, Di Palo A, Capurso A, Solfrizzi V. Effect of donepezil on the continuum of depressive symptoms, mild cognitive impairment, and progression to dementia. J Am Geriatr Soc. 2010 Feb;58(2):389-90. doi: 10.1111/j.1532-5415.2009.02702.x. No abstract available.
PMID: 20370868
citation: Ros T, Munneke MA, Ruge D, Gruzelier JH, Rothwell JC. Endogenous control of waking brain rhythms induces neuroplasticity in humans. Eur J Neurosci. 2010 Feb;31(4):770-8. doi: 10.1111/j.1460-9568.2010.07100.x.
PMID: 20384819
citation: Klimesch W. EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis. Brain Res Brain Res Rev. 1999 Apr;29(2-3):169-95. doi: 10.1016/s0165-0173(98)00056-3.
PMID: 10209231
citation: Jelic V, Johansson SE, Almkvist O, Shigeta M, Julin P, Nordberg A, Winblad B, Wahlund LO. Quantitative electroencephalography in mild cognitive impairment: longitudinal changes and possible prediction of Alzheimer's disease. Neurobiol Aging. 2000 Jul-Aug;21(4):533-40. doi: 10.1016/s0197-4580(00)00153-6.
PMID: 10924766
citation: Petersen RC, Caracciolo B, Brayne C, Gauthier S, Jelic V, Fratiglioni L. Mild cognitive impairment: a concept in evolution. J Intern Med. 2014 Mar;275(3):214-28. doi: 10.1111/joim.12190.
PMID: 24605806
citation: Association for Applied Psychophysiology and Biofeedback. Template for developing guidelines for the evaluation of the clinical efficacy of psychophysiological interventions. Appl Psychophysiol Biofeedback. 2002 Dec;27(4):273-81. doi: 10.1023/a:1021061318355.
PMID: 12557455
citation: Zoefel B, Huster RJ, Herrmann CS. Neurofeedback training of the upper alpha frequency band in EEG improves cognitive performance. Neuroimage. 2011 Jan 15;54(2):1427-31. doi: 10.1016/j.neuroimage.2010.08.078. Epub 2010 Sep 17.
PMID: 20850552
responsible party type: Principal Investigator
investigator affiliation: Beersheva Mental Health Center
investigator full name: Doron Todder
investigator title: Head of anxiety unit
mesh term: Alzheimer Disease
mesh term: Cognitive Dysfunction
sharing ipd: No