<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/NCT03778177</url>
  </required_header>
  <id_info>
    <org_study_id>TNP001</org_study_id>
    <nct_id>NCT03778177</nct_id>
  </id_info>
  <brief_title>Neurophysiologic Signatures of Trigeminal Neuralgia Pain</brief_title>
  <official_title>Mapping Towards a Cure - Identification of Neurophysiologic Signatures of Trigeminal Neuralgia Pain</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Florida</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Facial Pain Research Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Florida</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>
      Trigeminal neuralgia (TN) is an idiopathic pain disorder that is characterized by episodic&#xD;
      attacks of intense facial pain, described as paroxysms of stabbing, electric, or explosive&#xD;
      pain, and lasting for a few seconds or longer, often producing a tic-like facial movement,&#xD;
      and can occur up to hundreds of times per day. This pain is known to be one of the worst pain&#xD;
      conditions that a patient can suffer and has been called the &quot;suicide disease&quot;. Given the&#xD;
      severity of this disorder, determining the cause becomes essential for finding a cure. This&#xD;
      project will study the cause of TN using a translational approach, which means the research&#xD;
      project will be completed in both humans and animals. The investigators hypothesize that&#xD;
      there are specific areas of the brain and spinal cord that will provide a &quot;signature&quot; center&#xD;
      of activity. The study team will use state of the art magnetic resonance imaging (MRI)&#xD;
      machines and other non-invasive brain activity measurements, including electroencephalography&#xD;
      (EEG) to locate these centers in people with TN before and after their pain has started.&#xD;
      Recent studies have investigated the effects of transcranial electrical stimulation (tES) for&#xD;
      pain control. Transcranial electrical stimulation (tES) includes transcranial direct current&#xD;
      stimulation (tDCS) and transcranial alternating current stimulation (tACS). This approach is&#xD;
      important because identifying similar regions neural activity will allow for us to study&#xD;
      novel therapies in search of the cure for TN and this study has thus both basic and clinical&#xD;
      neuroscience significance.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Trigeminal neuralgia (TN) is an extremely painful and highly disabling orofacial pain&#xD;
      disorder, often referred to as the &quot;suicide disease,&quot; for which presently available therapies&#xD;
      are largely ineffective or inadequate. Both the unpredictable response to treatment and&#xD;
      variability in long-term clinical outcomes in TN strongly suggest that a range of peripheral&#xD;
      and central mechanisms remain to be understood. The long-term goal is to identify the&#xD;
      mechanisms involved in the initiation and progression of TN, and uncover rational targets for&#xD;
      the safe and effective treatment of TN. The objective of this application is to explore the&#xD;
      use of multimodal neuroimaging and neurophysiologic techniques in defining neural signatures&#xD;
      of the disease. Additionally, the study team wants to evaluate the efficacy of transcranial&#xD;
      electrical stimulation on relieving pain. The rationale for the proposed research is that&#xD;
      identification of signature peripheral and central activation sites will allow for&#xD;
      individualized treatment strategies for TN patients.&#xD;
&#xD;
      To modulate brain activities the investigators will use transcranial electrical stimulation&#xD;
      (tES). tES is an emerging neuromodulation technique that can be noninvasively and safely&#xD;
      applied in humans. tES can help better understand the causal roles of brain networks and&#xD;
      brain activities and has shown efficacy in improving pain. tES has two main variations:&#xD;
      transcranial direct current stimulation (tDCS) and transcranial alternating current&#xD;
      stimulation (tACS). The former applies a weak direct current to the scalp whereas the latter&#xD;
      applies a weak sinusoidal current to the scalp. tDCS can modulate the excitability of tissues&#xD;
      under the stimulating electrodes. tACS is particularly suited for interacting with various&#xD;
      oscillatory activities in the brain. tES has been used to study normal brain function and&#xD;
      treat neurological and pain disorders as well. There is demonstrated efficacy in improvement&#xD;
      of pain in subjects suffering from fibromyalgia and neuropathic pain. The study team will use&#xD;
      different tDCS/tACS montages targeting different brain regions and observe behavior and&#xD;
      neuronal activities. The current strength will be within 1mA or 2mA which has been shown to&#xD;
      be safe and effective.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2019</start_date>
  <completion_date type="Actual">May 12, 2022</completion_date>
  <primary_completion_date type="Actual">May 12, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>The investigators will use of transcranial electrical stimulation (tES) to evaluate pain in patients with Trigeminal Neuralgia (TN).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Effects of transcranial electrical stimulating (tES) on pain.</measure>
    <time_frame>Day 1</time_frame>
    <description>Pain will be measured by subjects using a visual analog scale (VAS). The VAS is a psychometric measuring instrument presented as a 100-mm horizontal line anchored on one end with the words &quot;no pain at all&quot; which is 0 and at the other end with the words &quot;worst pain imaginable&quot; which is 100. Subjects will be asked to rate their pain on the VAS from 0-100 once before the stimulation and again after the stimulation is complete. The two scores will be compared to see if there is any reduction in subject's pain after the stimulation.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">61</enrollment>
  <condition>Trigeminal Neuralgia (TN)</condition>
  <arm_group>
    <arm_group_label>Trigeminal Neuralgia Pain Diagnosis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy patients between the ages of 18-75 who have been diagnosed with moderate to severe Trigeminal Neuralgia Pain. The study team will perform transcranial electrical brain stimulation using either electrodes that are in the form of two salt-water soaked sponges attached to the head or a set of smaller gel-covered disk electrodes that fit inside the electrode holders of the EEG cap. During stimulation a weak direct or alternating current will be passed through the stimulating electrodes. Stimulation may last 20 to 30 minutes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>transcranial electrical brain stimulation</intervention_name>
    <description>Pain ratings will be recorded before and after transcranial brain electrical stimulation procedures using a Visual Analog Scale (VAS).</description>
    <arm_group_label>Trigeminal Neuralgia Pain Diagnosis</arm_group_label>
    <other_name>tES</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy subjects who have been diagnosed with trigeminal neuralgia (TN) pain (ASA&#xD;
             status 1, 2, or 3).&#xD;
&#xD;
          -  Subjects diagnosed with TN pain must have average pain in the moderate to severe&#xD;
             (Visual Analog Scale (VAS) of 30-100 mm) range. These subjects will be asked to stop&#xD;
             their current medications for 24 hours prior to their scan.&#xD;
&#xD;
          -  Patients diagnosed with classical trigeminal neuralgia, type 1 [TN1, G50.00], or&#xD;
             symptomatic trigeminal neuralgia [TN2, G53.80] according to the International&#xD;
             Classification of Headache (IHS) Disorders criteria (7).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients diagnosed with post-herpetic neuralgia, trigeminal neuropathic pain, and&#xD;
             trigeminal deafferentation pain.&#xD;
&#xD;
          -  TN subjects with ASA status 4-5 and Emergency operation.&#xD;
&#xD;
          -  Presence of chronic disease (e.g. cardiovascular disease, liver disease, kidney&#xD;
             disease, diabetes, etc.), other than trigeminal neuralgia.&#xD;
&#xD;
          -  Pregnant females&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John K Neubert, DDS, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Florida</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UF Health Shands Hospital</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McKnight Brain Institute</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Prasad S, Galetta S. Trigeminal neuralgia: historical notes and current concepts. Neurologist. 2009 Mar;15(2):87-94. doi: 10.1097/NRL.0b013e3181775ac3.</citation>
    <PMID>19276786</PMID>
  </reference>
  <reference>
    <citation>Lefaucheur JP, Antal A, Ayache SS, Benninger DH, Brunelin J, Cogiamanian F, Cotelli M, De Ridder D, Ferrucci R, Langguth B, Marangolo P, Mylius V, Nitsche MA, Padberg F, Palm U, Poulet E, Priori A, Rossi S, Schecklmann M, Vanneste S, Ziemann U, Garcia-Larrea L, Paulus W. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin Neurophysiol. 2017 Jan;128(1):56-92. doi: 10.1016/j.clinph.2016.10.087. Epub 2016 Oct 29.</citation>
    <PMID>27866120</PMID>
  </reference>
  <reference>
    <citation>O'Connell NE, Marston L, Spencer S, DeSouza LH, Wand BM. Non-invasive brain stimulation techniques for chronic pain. Cochrane Database Syst Rev. 2018 Apr 13;4(4):CD008208. doi: 10.1002/14651858.CD008208.pub5.</citation>
    <PMID>29652088</PMID>
  </reference>
  <reference>
    <citation>Chaieb L, Antal A, Pisoni A, Saiote C, Opitz A, Ambrus GG, Focke N, Paulus W. Safety of 5 kHz tACS. Brain Stimul. 2014 Jan-Feb;7(1):92-6. doi: 10.1016/j.brs.2013.08.004. Epub 2013 Sep 13.</citation>
    <PMID>24064065</PMID>
  </reference>
  <reference>
    <citation>Saltychev M, Laimi K. Effectiveness of repetitive transcranial magnetic stimulation in patients with fibromyalgia: a meta-analysis. Int J Rehabil Res. 2017 Mar;40(1):11-18. doi: 10.1097/MRR.0000000000000207.</citation>
    <PMID>27977465</PMID>
  </reference>
  <reference>
    <citation>Lefaucheur JP. The use of repetitive transcranial magnetic stimulation (rTMS) in chronic neuropathic pain. Neurophysiol Clin. 2006 May-Jun;36(3):117-24. doi: 10.1016/j.neucli.2006.08.002. Epub 2006 Aug 23.</citation>
    <PMID>17046606</PMID>
  </reference>
  <reference>
    <citation>Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013 Jul;33(9):629-808. doi: 10.1177/0333102413485658. No abstract available.</citation>
    <PMID>23771276</PMID>
  </reference>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>December 11, 2018</study_first_submitted>
  <study_first_submitted_qc>December 13, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>October 5, 2022</last_update_submitted>
  <last_update_submitted_qc>October 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>transcranial electrical stimulation (tES)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Trigeminal Neuralgia</mesh_term>
    <mesh_term>Neuralgia</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/NCT03778177
org study id: TNP001
nct id: NCT03778177
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Trigeminal neuralgia (TN) is an idiopathic pain disorder that is characterized by episodic
      attacks of intense facial pain, described as paroxysms of stabbing, electric, or explosive
      pain, and lasting for a few seconds or longer, often producing a tic-like facial movement,
      and can occur up to hundreds of times per day. This pain is known to be one of the worst pain
      conditions that a patient can suffer and has been called the "suicide disease". Given the
      severity of this disorder, determining the cause becomes essential for finding a cure. This
      project will study the cause of TN using a translational approach, which means the research
      project will be completed in both humans and animals. The investigators hypothesize that
      there are specific areas of the brain and spinal cord that will provide a "signature" center
      of activity. The study team will use state of the art magnetic resonance imaging (MRI)
      machines and other non-invasive brain activity measurements, including electroencephalography
      (EEG) to locate these centers in people with TN before and after their pain has started.
      Recent studies have investigated the effects of transcranial electrical stimulation (tES) for
      pain control. Transcranial electrical stimulation (tES) includes transcranial direct current
      stimulation (tDCS) and transcranial alternating current stimulation (tACS). This approach is
      important because identifying similar regions neural activity will allow for us to study
      novel therapies in search of the cure for TN and this study has thus both basic and clinical
      neuroscience significance.
Trigeminal neuralgia (TN) is an extremely painful and highly disabling orofacial pain
      disorder, often referred to as the "suicide disease," for which presently available therapies
      are largely ineffective or inadequate. Both the unpredictable response to treatment and
      variability in long-term clinical outcomes in TN strongly suggest that a range of peripheral
      and central mechanisms remain to be understood. The long-term goal is to identify the
      mechanisms involved in the initiation and progression of TN, and uncover rational targets for
      the safe and effective treatment of TN. The objective of this application is to explore the
      use of multimodal neuroimaging and neurophysiologic techniques in defining neural signatures
      of the disease. Additionally, the study team wants to evaluate the efficacy of transcranial
      electrical stimulation on relieving pain. The rationale for the proposed research is that
      identification of signature peripheral and central activation sites will allow for
      individualized treatment strategies for TN patients.

      To modulate brain activities the investigators will use transcranial electrical stimulation
      (tES). tES is an emerging neuromodulation technique that can be noninvasively and safely
      applied in humans. tES can help better understand the causal roles of brain networks and
      brain activities and has shown efficacy in improving pain. tES has two main variations:
      transcranial direct current stimulation (tDCS) and transcranial alternating current
      stimulation (tACS). The former applies a weak direct current to the scalp whereas the latter
      applies a weak sinusoidal current to the scalp. tDCS can modulate the excitability of tissues
      under the stimulating electrodes. tACS is particularly suited for interacting with various
      oscillatory activities in the brain. tES has been used to study normal brain function and
      treat neurological and pain disorders as well. There is demonstrated efficacy in improvement
      of pain in subjects suffering from fibromyalgia and neuropathic pain. The study team will use
      different tDCS/tACS montages targeting different brain regions and observe behavior and
      neuronal activities. The current strength will be within 1mA or 2mA which has been shown to
      be safe and effective.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: The investigators will use of transcranial electrical stimulation (tES) to evaluate pain in patients with Trigeminal Neuralgia (TN).
primary purpose: Treatment
masking: None (Open Label)
measure: Effects of transcranial electrical stimulating (tES) on pain.
time frame: Day 1
description: Pain will be measured by subjects using a visual analog scale (VAS). The VAS is a psychometric measuring instrument presented as a 100-mm horizontal line anchored on one end with the words "no pain at all" which is 0 and at the other end with the words "worst pain imaginable" which is 100. Subjects will be asked to rate their pain on the VAS from 0-100 once before the stimulation and again after the stimulation is complete. The two scores will be compared to see if there is any reduction in subject's pain after the stimulation.
arm group label: Trigeminal Neuralgia Pain Diagnosis
arm group type: Experimental
description: Healthy patients between the ages of 18-75 who have been diagnosed with moderate to severe Trigeminal Neuralgia Pain. The study team will perform transcranial electrical brain stimulation using either electrodes that are in the form of two salt-water soaked sponges attached to the head or a set of smaller gel-covered disk electrodes that fit inside the electrode holders of the EEG cap. During stimulation a weak direct or alternating current will be passed through the stimulating electrodes. Stimulation may last 20 to 30 minutes.
intervention type: Procedure
intervention name: transcranial electrical brain stimulation
description: Pain ratings will be recorded before and after transcranial brain electrical stimulation procedures using a Visual Analog Scale (VAS).
arm group label: Trigeminal Neuralgia Pain Diagnosis
other name: tES
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: John K Neubert, DDS, MS
role: Principal Investigator
affiliation: University of Florida
facility: 
facility: 
country: United States
citation: Prasad S, Galetta S. Trigeminal neuralgia: historical notes and current concepts. Neurologist. 2009 Mar;15(2):87-94. doi: 10.1097/NRL.0b013e3181775ac3.
PMID: 19276786
citation: Lefaucheur JP, Antal A, Ayache SS, Benninger DH, Brunelin J, Cogiamanian F, Cotelli M, De Ridder D, Ferrucci R, Langguth B, Marangolo P, Mylius V, Nitsche MA, Padberg F, Palm U, Poulet E, Priori A, Rossi S, Schecklmann M, Vanneste S, Ziemann U, Garcia-Larrea L, Paulus W. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin Neurophysiol. 2017 Jan;128(1):56-92. doi: 10.1016/j.clinph.2016.10.087. Epub 2016 Oct 29.
PMID: 27866120
citation: O'Connell NE, Marston L, Spencer S, DeSouza LH, Wand BM. Non-invasive brain stimulation techniques for chronic pain. Cochrane Database Syst Rev. 2018 Apr 13;4(4):CD008208. doi: 10.1002/14651858.CD008208.pub5.
PMID: 29652088
citation: Chaieb L, Antal A, Pisoni A, Saiote C, Opitz A, Ambrus GG, Focke N, Paulus W. Safety of 5 kHz tACS. Brain Stimul. 2014 Jan-Feb;7(1):92-6. doi: 10.1016/j.brs.2013.08.004. Epub 2013 Sep 13.
PMID: 24064065
citation: Saltychev M, Laimi K. Effectiveness of repetitive transcranial magnetic stimulation in patients with fibromyalgia: a meta-analysis. Int J Rehabil Res. 2017 Mar;40(1):11-18. doi: 10.1097/MRR.0000000000000207.
PMID: 27977465
citation: Lefaucheur JP. The use of repetitive transcranial magnetic stimulation (rTMS) in chronic neuropathic pain. Neurophysiol Clin. 2006 May-Jun;36(3):117-24. doi: 10.1016/j.neucli.2006.08.002. Epub 2006 Aug 23.
PMID: 17046606
citation: Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013 Jul;33(9):629-808. doi: 10.1177/0333102413485658. No abstract available.
PMID: 23771276
responsible party type: Sponsor
mesh term: Trigeminal Neuralgia
mesh term: Neuralgia
sharing ipd: No