<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/NCT03775252</url>
  </required_header>
  <id_info>
    <org_study_id>TrigeMigKeto</org_study_id>
    <nct_id>NCT03775252</nct_id>
  </id_info>
  <brief_title>A Ketogenic Diet Acts on Cortical But Not Subcortical Responsivity in Migraineurs</brief_title>
  <official_title>A Ketogenic Diet Normalizes Interictal Cortical But Not Subcortical Responsivity in Migraineurs</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>
      A short ketogenic diet (KD) treatment can prevent migraine attacks and correct excessive&#xD;
      cortical response. Here, investigators aim to prove if the KD-related changes of cortical&#xD;
      excitability are primarily due to cerebral cortex activity or are modulated by the brainstem.&#xD;
&#xD;
      Through the stimulation of the right supraorbital division of the trigeminal nerve, there&#xD;
      will be concurrently interictally recorded the nociceptive blink reflex (nBR) and the&#xD;
      pain-related evoked potentials (PREP) in 18 migraineurs patients without aura before and&#xD;
      after 1-month on KD, while in metabolic ketosis. nBR and PREP reflect distinct brain&#xD;
      structures activation: the brainstem and the cerebral cortex respectively. It will be&#xD;
      estimated nBR R2 component area-under-the-curve as well as PREP amplitude habituation as the&#xD;
      slope of the linear regression between the 1st and the 2nd block of 5 averaged responses.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2017</start_date>
  <completion_date type="Actual">November 30, 2017</completion_date>
  <primary_completion_date type="Actual">June 30, 2017</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>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Trigeminal neurophysiological changes (amplitude)</measure>
    <time_frame>one month</time_frame>
    <description>Comparison before and during ketogenic diet of trigeminal neurophysiological features in a population of patients with migraine. In particular, the nociceptive blink reflex (nBR) and the trigeminal pain-related evoked potentials (PREPs) changes of amplitude between the baseline (pre-diet) and during the diet will be used as markers of ketones activity on neural modulation. The unit of measure of the amplitude of neurophysiological evoked responses are the micronVolts (1 volt X 10^-6).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Trigeminal neurophysiological changes (latencies)</measure>
    <time_frame>one month</time_frame>
    <description>Comparison before and during ketogenic diet of latencies of trigeminal neurophysiological evoked responses in a population of patients with migraine. In particular, the latency of evoked nociceptive blink reflex (nBR) and the trigeminal pain-related evoked potentials (PREPs) changes between the baseline (pre-diet) and during the diet. The unit of measure of the latency of the neurophysiological features are the milliseconds (1 sec X 10^-3).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Trigeminal neurophysiological changes (slope)</measure>
    <time_frame>one month</time_frame>
    <description>Comparison before and during ketogenic diet of the habituation slope of amplitudes of repeated responses to repetitive trigeminal painful electrical stimuli in a population of patients with migraine. A repetitive stimulus induces repetitive responses from the brainstem and cerebral cortex that physiologically have a decremental trend of amplitudes, also called habituation. On the contrary, in migraineurs, there is a deficit of habituation, i.e. a lack of decremental responses, both in nociceptive blink reflex (nBR) and the trigeminal pain-related evoked potentials (PREPs). The changes induced by ketogenic diet in habituation slope will be measured. The unit of measure of the slope is the radiant degree.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Migraine Disorders</condition>
  <arm_group>
    <arm_group_label>Ketogenic diet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group of patients treated with ketogenic diet after the first neurophysiological screening.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Ketogenic diet</intervention_name>
    <description>Diet rich in fats and poor in carbohydrate, to induce metabolic ketosis</description>
    <arm_group_label>Ketogenic diet</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of migraine&#xD;
&#xD;
          -  Kept a headache diary for at least 1 month&#xD;
&#xD;
          -  Headache onset before the age of 50&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  over consumption of acute pain-killers (triptan, analgesic, or ergotamine)&#xD;
&#xD;
          -  pregnancy or lactation&#xD;
&#xD;
          -  type I diabetes&#xD;
&#xD;
          -  serious organic or psychiatric disorders that the investigators judged as having the&#xD;
             potential to influence the trial evaluation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>francesco Pierelli, MD</last_name>
    <role>Study Chair</role>
    <affiliation>University of Roma La Sapienza</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Policlinico Umberto I</name>
      <address>
        <city>Rome</city>
        <zip>00161</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <results_reference>
    <citation>Di Lorenzo C, Coppola G, Bracaglia M, Di Lenola D, Evangelista M, Sirianni G, Rossi P, Di Lorenzo G, Serrao M, Parisi V, Pierelli F. Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: a multimodal evoked potentials study. J Headache Pain. 2016;17:58. doi: 10.1186/s10194-016-0650-9. Epub 2016 May 31.</citation>
    <PMID>27245682</PMID>
  </results_reference>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 9, 2018</study_first_submitted>
  <study_first_submitted_qc>December 12, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 13, 2018</study_first_posted>
  <last_update_submitted>December 12, 2018</last_update_submitted>
  <last_update_submitted_qc>December 12, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 13, 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>Cherubino DI LORENZO</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Ketogenic Diet</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Migraine Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>There will be no sharing</ipd_description>
  </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/NCT03775252
org study id: TrigeMigKeto
nct id: NCT03775252
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A short ketogenic diet (KD) treatment can prevent migraine attacks and correct excessive
      cortical response. Here, investigators aim to prove if the KD-related changes of cortical
      excitability are primarily due to cerebral cortex activity or are modulated by the brainstem.

      Through the stimulation of the right supraorbital division of the trigeminal nerve, there
      will be concurrently interictally recorded the nociceptive blink reflex (nBR) and the
      pain-related evoked potentials (PREP) in 18 migraineurs patients without aura before and
      after 1-month on KD, while in metabolic ketosis. nBR and PREP reflect distinct brain
      structures activation: the brainstem and the cerebral cortex respectively. It will be
      estimated nBR R2 component area-under-the-curve as well as PREP amplitude habituation as the
      slope of the linear regression between the 1st and the 2nd block of 5 averaged responses.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Trigeminal neurophysiological changes (amplitude)
time frame: one month
description: Comparison before and during ketogenic diet of trigeminal neurophysiological features in a population of patients with migraine. In particular, the nociceptive blink reflex (nBR) and the trigeminal pain-related evoked potentials (PREPs) changes of amplitude between the baseline (pre-diet) and during the diet will be used as markers of ketones activity on neural modulation. The unit of measure of the amplitude of neurophysiological evoked responses are the micronVolts (1 volt X 10^-6).
measure: Trigeminal neurophysiological changes (latencies)
time frame: one month
description: Comparison before and during ketogenic diet of latencies of trigeminal neurophysiological evoked responses in a population of patients with migraine. In particular, the latency of evoked nociceptive blink reflex (nBR) and the trigeminal pain-related evoked potentials (PREPs) changes between the baseline (pre-diet) and during the diet. The unit of measure of the latency of the neurophysiological features are the milliseconds (1 sec X 10^-3).
measure: Trigeminal neurophysiological changes (slope)
time frame: one month
description: Comparison before and during ketogenic diet of the habituation slope of amplitudes of repeated responses to repetitive trigeminal painful electrical stimuli in a population of patients with migraine. A repetitive stimulus induces repetitive responses from the brainstem and cerebral cortex that physiologically have a decremental trend of amplitudes, also called habituation. On the contrary, in migraineurs, there is a deficit of habituation, i.e. a lack of decremental responses, both in nociceptive blink reflex (nBR) and the trigeminal pain-related evoked potentials (PREPs). The changes induced by ketogenic diet in habituation slope will be measured. The unit of measure of the slope is the radiant degree.
arm group label: Ketogenic diet
arm group type: Experimental
description: Group of patients treated with ketogenic diet after the first neurophysiological screening.
intervention type: Dietary Supplement
intervention name: Ketogenic diet
description: Diet rich in fats and poor in carbohydrate, to induce metabolic ketosis
arm group label: Ketogenic diet
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: francesco Pierelli, MD
role: Study Chair
affiliation: University of Roma La Sapienza
facility: 
country: Italy
citation: Di Lorenzo C, Coppola G, Bracaglia M, Di Lenola D, Evangelista M, Sirianni G, Rossi P, Di Lorenzo G, Serrao M, Parisi V, Pierelli F. Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: a multimodal evoked potentials study. J Headache Pain. 2016;17:58. doi: 10.1186/s10194-016-0650-9. Epub 2016 May 31.
PMID: 27245682
responsible party type: Principal Investigator
investigator affiliation: University of Roma La Sapienza
investigator full name: Cherubino DI LORENZO
investigator title: Principal Investigator
mesh term: Migraine Disorders
sharing ipd: No
ipd description: There will be no sharing