<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/NCT03832413</url>
  </required_header>
  <id_info>
    <org_study_id>QuantalX_pilot_asaf_harophe</org_study_id>
    <nct_id>NCT03832413</nct_id>
  </id_info>
  <brief_title>Characterization of the DELPhI System in Assessing Brain's Functionality in Different Neurological Disorders</brief_title>
  <official_title>Characterization of the DELPhI System in Assessing Brain's Functionality in Different Neurological Disorders-A Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>QuantalX Neuroscience</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>QuantalX Neuroscience</source>
  <oversight_info>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      We use Transcranial magnetic stimulation (TMS), combined with simultaneous registration of&#xD;
      electroencephalograph (EEG),for examining human cortical functionality. TMS-EEG is a&#xD;
      noninvasive brain stimulation method that allows to study human cortical function in vivo.&#xD;
      EEG provides an opportunity to directly measure the cerebral response to TMS, measuring the&#xD;
      cortical TMS Evoked potential (TEP). In this study we measure TEPs, in a wide variety of&#xD;
      neurological conditions and healthy as a measure of cerebral reactivity across wide areas of&#xD;
      neocortex.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Brain network plasticity evaluation has been shown extensively essential for understanding&#xD;
      and monitoring of brain functional changes and brain disorders. However, existing clinically&#xD;
      used imaging methods are unable to robustly indicate plasticity or plasticity changes.&#xD;
      Therefore, there is a great need for developing such an imaging tool for brain functional&#xD;
      evaluation. In basic neuroscience research plasticity evaluation is performed by conducting&#xD;
      electrophysiological measurements in vivo. By using EEG - combined with TMS stimulation this&#xD;
      methodology can be transformed into clinically used plasticity and connectivity assessment&#xD;
      for evaluation of functional brain status. This study may thus introduce a novel,&#xD;
      non-invasive and efficient method for brain functional imaging. DELPhI evaluation will offer&#xD;
      a true multimodality imaging by combining EEG and TMS that allows a quantative objective and&#xD;
      direct identification of disease assessment. There is a real unmet need for an accurate and&#xD;
      objective evaluation that together with the common clinical practice will provide&#xD;
      neurologists and psychiatrists a more definite and personalized treatment prescription.&#xD;
&#xD;
      Studies integrating TMS with EEG (TMS-EEG) have shown that TMS produces waves of activity&#xD;
      that reverberate throughout the cortex and that are reproducible and reliable thus providing&#xD;
      direct information about cortical excitability and connectivity with excellent time&#xD;
      resolution. By evaluating the propagation of evoked activity in different behavioral states&#xD;
      and in different tasks, TMS-EEG has been used to causally probe the dynamic effective&#xD;
      connectivity of human brain networks. When applying the TMS coil above the motor cortex, a&#xD;
      cascade effect called the motor-evoked potential (MEP), is initiated. The MEP is measurable&#xD;
      at peripheral muscles. The Motor cortex is a brain structure located between the frontal and&#xD;
      parietal cortices. Pyramidal neurons in the motor cortex, upper motor neuron going through&#xD;
      the brain stem, send signals to lower motor neuron in the spinal cord which stimulate muscle&#xD;
      fibers. TMS stimulus to the Motor cortex evokes a brain response which propagates to&#xD;
      different brain regions in addition to the peripheral limb muscles [20]. An important feature&#xD;
      of TEP topography is that even though only one cortical hemisphere is stimulated,&#xD;
      bihemispheric EEG evoked responses are evoked with different features. TMS-evoked activity&#xD;
      propagates from the stimulation site ipsilaterally via association fibers and contralaterally&#xD;
      via transcallosal fibers and to subcortical structures via projection fibers. These&#xD;
      TMS-evoked cortical potentials (TEPs) last for up to 300 ms in both the vicinity of the&#xD;
      stimulation as well as in remote interconnected brain areas reflect long term changes in&#xD;
      cortical network excitation-inhibition balance refeed to as brain network plasticity. A&#xD;
      single TMS pulse delivered over the primary motor cortex (M1) results in a sequence of&#xD;
      positive and negative EEG peaks at specific latencies (i.e., P25, N45, P70, N100, and P180).&#xD;
&#xD;
      In this study a wide population of subjects will be recruited. this population will include&#xD;
      different neurological conditions and healthy subjects, arriving to the Hyperbaric center at&#xD;
      Asaf-Harophe hospital. Each subject will be tested once before treatment initiation and&#xD;
      subsequent tests will be performed also after treatment termination or at follow up time&#xD;
      points. Each evaluation will last up to 90 minutes and will include affixed stimulation&#xD;
      protocol ranging Up to 1000 TMS pulses, with intensities between 60-130% of motor threshold&#xD;
      (MT). Inter-stimuli frequency will change from 0.01 up to 20 Hz.Existing clinical data such&#xD;
      as MRI scans, neurocognitive assessments and clinical evaluations will be collected out of&#xD;
      patient files. EEG data recorded will be analyzed and corrolations to the clinical data will&#xD;
      be tested.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 23, 2018</start_date>
  <completion_date type="Actual">February 14, 2022</completion_date>
  <primary_completion_date type="Actual">February 14, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Correlation between DELPhI's parameters to MRI scans</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>Correlation between DELPhI parameters to cognitive assessment by MRI/CT and computerized cognitive evaluation (Mindstreems cognitive battery test).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Correlation between DELPhI's parameters to cognitive assessment</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>Correlation between DELPhI parameters to MRI/CT and computerized cognitive evaluation (Mindstreems cognitive battery test).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cluster TMS Evoked Responses' (TEPs') features such as amplitude, latency, Area under the curve and slopes.</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>Calculating potential clusters based on TEP's features at different stimulation conditions. Features such as amplitude, area under the curve, slope and latency.</description>
  </secondary_outcome>
  <number_of_groups>10</number_of_groups>
  <enrollment type="Actual">193</enrollment>
  <condition>Stroke</condition>
  <condition>TBI</condition>
  <condition>Fibromyalgia</condition>
  <condition>PDD</condition>
  <condition>Adhd</condition>
  <condition>ABD</condition>
  <condition>Ptsd</condition>
  <condition>Healthy</condition>
  <condition>MCI</condition>
  <condition>Dementia</condition>
  <condition>Cognitive Impairment</condition>
  <condition>Cognitive Decline</condition>
  <arm_group>
    <arm_group_label>Stroke</arm_group_label>
    <description>Diagnostic Test: DELPhI (TMS-EEG analysis)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TBI</arm_group_label>
    <description>Diagnostic Test: DELPhI (TMS-EEG analysis)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ABD</arm_group_label>
    <description>Diagnostic Test: DELPhI (TMS-EEG analysis)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fibromyalgia</arm_group_label>
    <description>Diagnostic Test: DELPhI (TMS-EEG analysis)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PDD</arm_group_label>
    <description>Diagnostic Test: DELPhI (TMS-EEG analysis)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ADHD</arm_group_label>
    <description>Diagnostic Test: DELPhI (TMS-EEG analysis)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MCI</arm_group_label>
    <description>Diagnostic Test: DELPhI (TMS-EEG analysis)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dementia</arm_group_label>
    <description>Diagnostic Test: DELPhI (TMS-EEG analysis)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy</arm_group_label>
    <description>Diagnostic Test: DELPhI (TMS-EEG analysis)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cognitive impairment</arm_group_label>
    <description>Diagnostic Test: DELPhI (TMS-EEG analysis)</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>DELPhI (TMS-EEG analysis)</intervention_name>
    <description>We perform an evaluation not an intervention. the DELPhI evaluation comprises of an automated analysis to EEG data recorded during TMS (Transcranial Magnetic Stimulation) to the M1L (Primary motor cortex).</description>
    <arm_group_label>ABD</arm_group_label>
    <arm_group_label>ADHD</arm_group_label>
    <arm_group_label>Cognitive impairment</arm_group_label>
    <arm_group_label>Dementia</arm_group_label>
    <arm_group_label>Fibromyalgia</arm_group_label>
    <arm_group_label>Healthy</arm_group_label>
    <arm_group_label>MCI</arm_group_label>
    <arm_group_label>PDD</arm_group_label>
    <arm_group_label>Stroke</arm_group_label>
    <arm_group_label>TBI</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients arriving to the Sagol center for Hyperbaric medicine at Assaf harofe Medical&#xD;
        center, undergoing a series of hyperbaric treatment sessions and will be found compatible&#xD;
        to inclusion/exclusion criteria.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Man and woman at the ages of ≥18 years.&#xD;
&#xD;
          2. Designated to perform a neurocognitive evaluation at the Sagol center for hyperbaric&#xD;
             medicine and research, at Assaf-Harofe Medical center.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Under 18 years of age.&#xD;
&#xD;
          2. With a skin condition on the scalp preventing the placement of EEG cap.&#xD;
&#xD;
          3. Pregnant or breastfeeding woman.&#xD;
&#xD;
          4. Unable to give an informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Asaf-Harophe</name>
      <address>
        <city>Rishon LeZion</city>
        <zip>70300</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>November 1, 2018</study_first_submitted>
  <study_first_submitted_qc>February 5, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 6, 2019</study_first_posted>
  <last_update_submitted>February 15, 2022</last_update_submitted>
  <last_update_submitted_qc>February 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fibromyalgia</mesh_term>
    <mesh_term>Nervous System Diseases</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03832413
org study id: QuantalX_pilot_asaf_harophe
nct id: NCT03832413
lead sponsor: 
is fda regulated device: Yes
is us export: No
We use Transcranial magnetic stimulation (TMS), combined with simultaneous registration of
      electroencephalograph (EEG),for examining human cortical functionality. TMS-EEG is a
      noninvasive brain stimulation method that allows to study human cortical function in vivo.
      EEG provides an opportunity to directly measure the cerebral response to TMS, measuring the
      cortical TMS Evoked potential (TEP). In this study we measure TEPs, in a wide variety of
      neurological conditions and healthy as a measure of cerebral reactivity across wide areas of
      neocortex.
Brain network plasticity evaluation has been shown extensively essential for understanding
      and monitoring of brain functional changes and brain disorders. However, existing clinically
      used imaging methods are unable to robustly indicate plasticity or plasticity changes.
      Therefore, there is a great need for developing such an imaging tool for brain functional
      evaluation. In basic neuroscience research plasticity evaluation is performed by conducting
      electrophysiological measurements in vivo. By using EEG - combined with TMS stimulation this
      methodology can be transformed into clinically used plasticity and connectivity assessment
      for evaluation of functional brain status. This study may thus introduce a novel,
      non-invasive and efficient method for brain functional imaging. DELPhI evaluation will offer
      a true multimodality imaging by combining EEG and TMS that allows a quantative objective and
      direct identification of disease assessment. There is a real unmet need for an accurate and
      objective evaluation that together with the common clinical practice will provide
      neurologists and psychiatrists a more definite and personalized treatment prescription.

      Studies integrating TMS with EEG (TMS-EEG) have shown that TMS produces waves of activity
      that reverberate throughout the cortex and that are reproducible and reliable thus providing
      direct information about cortical excitability and connectivity with excellent time
      resolution. By evaluating the propagation of evoked activity in different behavioral states
      and in different tasks, TMS-EEG has been used to causally probe the dynamic effective
      connectivity of human brain networks. When applying the TMS coil above the motor cortex, a
      cascade effect called the motor-evoked potential (MEP), is initiated. The MEP is measurable
      at peripheral muscles. The Motor cortex is a brain structure located between the frontal and
      parietal cortices. Pyramidal neurons in the motor cortex, upper motor neuron going through
      the brain stem, send signals to lower motor neuron in the spinal cord which stimulate muscle
      fibers. TMS stimulus to the Motor cortex evokes a brain response which propagates to
      different brain regions in addition to the peripheral limb muscles [20]. An important feature
      of TEP topography is that even though only one cortical hemisphere is stimulated,
      bihemispheric EEG evoked responses are evoked with different features. TMS-evoked activity
      propagates from the stimulation site ipsilaterally via association fibers and contralaterally
      via transcallosal fibers and to subcortical structures via projection fibers. These
      TMS-evoked cortical potentials (TEPs) last for up to 300 ms in both the vicinity of the
      stimulation as well as in remote interconnected brain areas reflect long term changes in
      cortical network excitation-inhibition balance refeed to as brain network plasticity. A
      single TMS pulse delivered over the primary motor cortex (M1) results in a sequence of
      positive and negative EEG peaks at specific latencies (i.e., P25, N45, P70, N100, and P180).

      In this study a wide population of subjects will be recruited. this population will include
      different neurological conditions and healthy subjects, arriving to the Hyperbaric center at
      Asaf-Harophe hospital. Each subject will be tested once before treatment initiation and
      subsequent tests will be performed also after treatment termination or at follow up time
      points. Each evaluation will last up to 90 minutes and will include affixed stimulation
      protocol ranging Up to 1000 TMS pulses, with intensities between 60-130% of motor threshold
      (MT). Inter-stimuli frequency will change from 0.01 up to 20 Hz.Existing clinical data such
      as MRI scans, neurocognitive assessments and clinical evaluations will be collected out of
      patient files. EEG data recorded will be analyzed and corrolations to the clinical data will
      be tested.
observational model: Cohort
time perspective: Prospective
measure: Correlation between DELPhI's parameters to MRI scans
time frame: through study completion, an average of 1 year
description: Correlation between DELPhI parameters to cognitive assessment by MRI/CT and computerized cognitive evaluation (Mindstreems cognitive battery test).
measure: Correlation between DELPhI's parameters to cognitive assessment
time frame: through study completion, an average of 1 year
description: Correlation between DELPhI parameters to MRI/CT and computerized cognitive evaluation (Mindstreems cognitive battery test).
measure: Cluster TMS Evoked Responses' (TEPs') features such as amplitude, latency, Area under the curve and slopes.
time frame: through study completion, an average of 1 year
description: Calculating potential clusters based on TEP's features at different stimulation conditions. Features such as amplitude, area under the curve, slope and latency.
arm group label: Stroke
description: Diagnostic Test: DELPhI (TMS-EEG analysis)
arm group label: TBI
description: Diagnostic Test: DELPhI (TMS-EEG analysis)
arm group label: ABD
description: Diagnostic Test: DELPhI (TMS-EEG analysis)
arm group label: Fibromyalgia
description: Diagnostic Test: DELPhI (TMS-EEG analysis)
arm group label: PDD
description: Diagnostic Test: DELPhI (TMS-EEG analysis)
arm group label: ADHD
description: Diagnostic Test: DELPhI (TMS-EEG analysis)
arm group label: MCI
description: Diagnostic Test: DELPhI (TMS-EEG analysis)
arm group label: Dementia
description: Diagnostic Test: DELPhI (TMS-EEG analysis)
arm group label: Healthy
description: Diagnostic Test: DELPhI (TMS-EEG analysis)
arm group label: Cognitive impairment
description: Diagnostic Test: DELPhI (TMS-EEG analysis)
intervention type: Diagnostic Test
intervention name: DELPhI (TMS-EEG analysis)
description: We perform an evaluation not an intervention. the DELPhI evaluation comprises of an automated analysis to EEG data recorded during TMS (Transcranial Magnetic Stimulation) to the M1L (Primary motor cortex).
arm group label: ABD
arm group label: ADHD
arm group label: Cognitive impairment
arm group label: Dementia
arm group label: Fibromyalgia
arm group label: Healthy
arm group label: MCI
arm group label: PDD
arm group label: Stroke
arm group label: TBI
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Israel
responsible party type: Sponsor
mesh term: Fibromyalgia
mesh term: Nervous System Diseases
mesh term: Cognitive Dysfunction