xml: <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/NCT06013761</url>
    </required_header>
    <id_info>
      <org_study_id>23-92 BO</org_study_id>
      <nct_id>NCT06013761</nct_id>
    </id_info>
    <brief_title>IF-MCT 16:8: Investigating the Influence of Intermittent Fasting With and Without MCTs in Patients With Drug-resistant Epilepsy</brief_title>
    <acronym>IF-MCT16:8</acronym>
    <official_title>Monocentric Randomized Experimental Pilot Trial Investigating the Influence of Intermittent Fasting According to the 16:8 Method With and Without Medium-chain Triglycerides (MCTs) on Seizure Frequency, Biomarkers and Neural Networks in Patients With Drug-resistant Epilepsy</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Hospital Marburg</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University Hospital Marburg</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>
        The objective of the prospective monocentric pilot trial is to investigate the influence of&#xD;
        intermittent fasting with or without a once-daily intake with medium chain triglycerides&#xD;
        (MCTs) on the frequency of seizures in patients with therapy-refractory epilepsy. The effects&#xD;
        of 12 weeks intermittent fasting according to the 16:8 method (IF 16:8) are compared to 12&#xD;
        weeks intermittent fasting with additional intake of exogenous MCTs (IF MCT 16:8) in a&#xD;
        within-subject-crossover-design in 28 patients with drug-resistant epilepsy.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        One in three patients suffering epilepsy does not become seizure-free with conventional&#xD;
        pharmacotherapy. The chance of seizure freedom with each additional medication is only in the&#xD;
        single-digit percentage range. For this reason, additive therapies such as the ketogenic diet&#xD;
        play an important role. By means of a ketogenic diet, a significant reduction in the&#xD;
        frequency of seizures has been shown in various studies for children. The main goal is the&#xD;
        body's own production of ketone bodies in the liver, which are used instead of glucose to&#xD;
        produce the energy carrier ATP. This metabolic change results in biochemical, metabolic and&#xD;
        hormonal changes that may reduce the severity and frequency of epileptic seizures, although&#xD;
        the exact mechanisms are not yet understood. Common to all forms of ketogenic diets (e.g.&#xD;
        classic kKD, modified Atkins diet, low glycemic index diet) is a specific preparation of each&#xD;
        meal with plans for meals and often an initiation of additive therapy in the inpatient&#xD;
        setting or by trained staff. Especially in adulthood, the lack of treatment adherence seems&#xD;
        to play an important role in the effectiveness of the ketogenic diet. A form of ketogenic&#xD;
        diet which might be more suitable for everyday use is intermittent fasting.&#xD;
  &#xD;
        The primary aim of the prospective monocentric pilot trial is to investigate the effect of&#xD;
        intermittent fasting with and without a once-daily intake of medium-chain triglycerides&#xD;
        (MCTs) on the frequency of seizures in patients with therapy-refractory epilepsy. The effects&#xD;
        of 12 weeks intermittent fasting according to the 16:8 method (IF 16:8) are compared to 12&#xD;
        weeks intermittent fasting with additional intake of exogenous medium chain triglycerides (IF&#xD;
        MCT 16:8) in a within-subject-crossover design in 28 patients with drug-resistant epilepsy.&#xD;
        Secondarily, the influence of this diet on the composition of the gut microbiome, the T-cell&#xD;
        mediated innate immune system and neuronal signalling pathways and networks will be&#xD;
        investigated.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 25, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2025</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>Crossover Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Effect of intermittent fasting according to the 16:8 method with and without exogenous MCTs on seizure frequency in drug-resistant epilepsy</measure>
      <time_frame>3 months</time_frame>
      <description>Monthly seizure frequency is recorded using standardized seizure diaries.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Effect of intermittent fasting according to the 16:8 method on therapy adherence in patients with drug-resistant epilepsy</measure>
      <time_frame>3 months</time_frame>
      <description>The nutritional behavior during the studio is recorded using a standardized daily nutrition diary.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on ketosis in patients with drug-resistant epilepsy</measure>
      <time_frame>3 months</time_frame>
      <description>All participants measure their ketosis weekly with a standardized ketosis device during the fasting episode and document this in a ketosis table provided.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effect of intermittent fasting according to the 16:8 method on self-efficacy in patients with drug-resistant epilepsy</measure>
      <time_frame>3 months</time_frame>
      <description>Self-efficacy is determined using the scale of general self-efficacy expectation (Jerusalem &amp; Schwarzer). This includes 10 items with 4 degrees. High scores mean a high level of general self-efficacy expectation.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effect of intermittent fasting according to the 16:8 method on life-quality in patients with drug-resistant epilepsy</measure>
      <time_frame>3 months</time_frame>
      <description>Life-quality is measured using the standardized questionnaire on life quality.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on biomarkers in patients with drug-resistant epilepsy</measure>
      <time_frame>3 months</time_frame>
      <description>The metabolome is examined using a mass spectroscopic blood sample. The microbiome is examined using a standardized stool sample using next-generation sequencing.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on neural networks in patients with drug-resistant epilepsy</measure>
      <time_frame>3 months</time_frame>
      <description>Neural networks are measured using magnetic resonance imaging (diffusion tensor imaging and resting state MRI).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on immune status in patients with drug-resistant epilepsy</measure>
      <time_frame>3 months</time_frame>
      <description>The immune status and in particular the T-cell mediated innate immune response is determined serologically.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on fatigue in patients with drug-resistant epilepsy</measure>
      <time_frame>3 months</time_frame>
      <description>Fatigue is measured using the standardized Fatigue-Impact-Scale (FIS)-Test.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on attention in patients with drug-resistant epilepsy</measure>
      <time_frame>3 months</time_frame>
      <description>Attention is measured using the standardized test battery for attention testing (TAP-Test).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on neurotransmitter gamma-aminobutyric acid (GABA)in patients with drug-resistant epilepsy</measure>
      <time_frame>3 months</time_frame>
      <description>The change in the neurotransmitter GABA is examined serologically over the period of the study phase.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on stress response in patients with drug-resistant epilepsy</measure>
      <time_frame>3 months</time_frame>
      <description>Stress response in hair cortisol of all participants is recorded using several hair samples.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on intima media thickness in patients with drug-resistant epilepsy</measure>
      <time_frame>3 months</time_frame>
      <description>Intima media thickness of all participants will be recorded with a duplex sonographic examination of the arteries supplying the brain.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">28</enrollment>
    <condition>Epilepsy</condition>
    <condition>Intermittent Fasting</condition>
    <arm_group>
      <arm_group_label>IF 16:8</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>12 weeks intermittent fasting according to the 16:8 method (IF 16:8)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>IF MCT 16:8</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>12 weeks intermittent fasting with additional intake of exogenous MCTs (IF MCT 16:8)</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>IF 16:8 as active comparator vs. IF MCT 16:8 as experimental arm</intervention_name>
      <description>12 weeks intermittent fasting according to the 16:8 method (IF 16:8) are compared with 12 weeks intermittent fasting with additional intake of exogenous MCTs (IF MCT 16:8) in a within-subject-crossover design in 28 patients with drug-resistant epilepsy. In order to enable the highest possible adherence, there are no restrictions on the composition of the food.</description>
      <arm_group_label>IF 16:8</arm_group_label>
      <arm_group_label>IF MCT 16:8</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Subjects able to provide informed consent&#xD;
  &#xD;
            -  Drug-resistant epilepsy&#xD;
  &#xD;
            -  At least 3 seizures per month&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Pregnancy&#xD;
  &#xD;
            -  Breast feeding period&#xD;
  &#xD;
            -  Metabolic disorder (e.g. diabetes, liver cirrhosis, kidney disease)&#xD;
  &#xD;
            -  Eating Disorder (e.g. anorexia, bulimia)&#xD;
  &#xD;
            -  Chronic inflammatory gut disease&#xD;
  &#xD;
            -  Active cancerous disease&#xD;
  &#xD;
            -  Antibiotics within the last 3 months&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Wiebke Hahn, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Philipps University Marburg Medical Center</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Wiebke Hahn, MD</last_name>
      <phone>+49 642158 65348</phone>
      <email>Hahnwi@staff.uni-marburg.de</email>
    </overall_contact>
    <location>
      <facility>
        <name>Philipps University Marburg, Faculty of Medicine, Department of Neurology, Epilepsy Center</name>
        <address>
          <city>Marburg</city>
          <state>Hessen</state>
          <zip>Baldingerstr., 35043</zip>
          <country>Germany</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Department of Neurology, Epilepsy Center</last_name>
        <phone>+49 6421 5865348</phone>
        <email>ezm@med.uni-marburg.de</email>
      </contact>
    </location>
    <location_countries>
      <country>Germany</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 8, 2023</study_first_submitted>
    <study_first_submitted_qc>August 24, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>August 24, 2023</last_update_submitted>
    <last_update_submitted_qc>August 24, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Philipps University Marburg Medical Center</investigator_affiliation>
      <investigator_full_name>Susanne Knake</investigator_full_name>
      <investigator_title>Principal investigator</investigator_title>
    </responsible_party>
    <keyword>Drug-resistant epilepsy</keyword>
    <keyword>Intermittent fasting</keyword>
    <keyword>Seizure frequency</keyword>
    <keyword>Biomarkers</keyword>
    <keyword>Neural networks</keyword>
    <keyword>Microbiome</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Epilepsy</mesh_term>
      <mesh_term>Drug Resistant Epilepsy</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06013761
  org study id: 23-92 BO
  nct id: NCT06013761
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The objective of the prospective monocentric pilot trial is to investigate the influence of
        intermittent fasting with or without a once-daily intake with medium chain triglycerides
        (MCTs) on the frequency of seizures in patients with therapy-refractory epilepsy. The effects
        of 12 weeks intermittent fasting according to the 16:8 method (IF 16:8) are compared to 12
        weeks intermittent fasting with additional intake of exogenous MCTs (IF MCT 16:8) in a
        within-subject-crossover-design in 28 patients with drug-resistant epilepsy.
  One in three patients suffering epilepsy does not become seizure-free with conventional
        pharmacotherapy. The chance of seizure freedom with each additional medication is only in the
        single-digit percentage range. For this reason, additive therapies such as the ketogenic diet
        play an important role. By means of a ketogenic diet, a significant reduction in the
        frequency of seizures has been shown in various studies for children. The main goal is the
        body's own production of ketone bodies in the liver, which are used instead of glucose to
        produce the energy carrier ATP. This metabolic change results in biochemical, metabolic and
        hormonal changes that may reduce the severity and frequency of epileptic seizures, although
        the exact mechanisms are not yet understood. Common to all forms of ketogenic diets (e.g.
        classic kKD, modified Atkins diet, low glycemic index diet) is a specific preparation of each
        meal with plans for meals and often an initiation of additive therapy in the inpatient
        setting or by trained staff. Especially in adulthood, the lack of treatment adherence seems
        to play an important role in the effectiveness of the ketogenic diet. A form of ketogenic
        diet which might be more suitable for everyday use is intermittent fasting.
  
        The primary aim of the prospective monocentric pilot trial is to investigate the effect of
        intermittent fasting with and without a once-daily intake of medium-chain triglycerides
        (MCTs) on the frequency of seizures in patients with therapy-refractory epilepsy. The effects
        of 12 weeks intermittent fasting according to the 16:8 method (IF 16:8) are compared to 12
        weeks intermittent fasting with additional intake of exogenous medium chain triglycerides (IF
        MCT 16:8) in a within-subject-crossover design in 28 patients with drug-resistant epilepsy.
        Secondarily, the influence of this diet on the composition of the gut microbiome, the T-cell
        mediated innate immune system and neuronal signalling pathways and networks will be
        investigated.
  allocation: Randomized
  intervention model: Crossover Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Effect of intermittent fasting according to the 16:8 method with and without exogenous MCTs on seizure frequency in drug-resistant epilepsy
  time frame: 3 months
  description: Monthly seizure frequency is recorded using standardized seizure diaries.
  measure: Effect of intermittent fasting according to the 16:8 method on therapy adherence in patients with drug-resistant epilepsy
  time frame: 3 months
  description: The nutritional behavior during the studio is recorded using a standardized daily nutrition diary.
  measure: Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on ketosis in patients with drug-resistant epilepsy
  time frame: 3 months
  description: All participants measure their ketosis weekly with a standardized ketosis device during the fasting episode and document this in a ketosis table provided.
  measure: Effect of intermittent fasting according to the 16:8 method on self-efficacy in patients with drug-resistant epilepsy
  time frame: 3 months
  description: Self-efficacy is determined using the scale of general self-efficacy expectation (Jerusalem & Schwarzer). This includes 10 items with 4 degrees. High scores mean a high level of general self-efficacy expectation.
  measure: Effect of intermittent fasting according to the 16:8 method on life-quality in patients with drug-resistant epilepsy
  time frame: 3 months
  description: Life-quality is measured using the standardized questionnaire on life quality.
  measure: Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on biomarkers in patients with drug-resistant epilepsy
  time frame: 3 months
  description: The metabolome is examined using a mass spectroscopic blood sample. The microbiome is examined using a standardized stool sample using next-generation sequencing.
  measure: Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on neural networks in patients with drug-resistant epilepsy
  time frame: 3 months
  description: Neural networks are measured using magnetic resonance imaging (diffusion tensor imaging and resting state MRI).
  measure: Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on immune status in patients with drug-resistant epilepsy
  time frame: 3 months
  description: The immune status and in particular the T-cell mediated innate immune response is determined serologically.
  measure: Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on fatigue in patients with drug-resistant epilepsy
  time frame: 3 months
  description: Fatigue is measured using the standardized Fatigue-Impact-Scale (FIS)-Test.
  measure: Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on attention in patients with drug-resistant epilepsy
  time frame: 3 months
  description: Attention is measured using the standardized test battery for attention testing (TAP-Test).
  measure: Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on neurotransmitter gamma-aminobutyric acid (GABA)in patients with drug-resistant epilepsy
  time frame: 3 months
  description: The change in the neurotransmitter GABA is examined serologically over the period of the study phase.
  measure: Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on stress response in patients with drug-resistant epilepsy
  time frame: 3 months
  description: Stress response in hair cortisol of all participants is recorded using several hair samples.
  measure: Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on intima media thickness in patients with drug-resistant epilepsy
  time frame: 3 months
  description: Intima media thickness of all participants will be recorded with a duplex sonographic examination of the arteries supplying the brain.
  arm group label: IF 16:8
  arm group type: Active Comparator
  description: 12 weeks intermittent fasting according to the 16:8 method (IF 16:8)
  arm group label: IF MCT 16:8
  arm group type: Experimental
  description: 12 weeks intermittent fasting with additional intake of exogenous MCTs (IF MCT 16:8)
  intervention type: Other
  intervention name: IF 16:8 as active comparator vs. IF MCT 16:8 as experimental arm
  description: 12 weeks intermittent fasting according to the 16:8 method (IF 16:8) are compared with 12 weeks intermittent fasting with additional intake of exogenous MCTs (IF MCT 16:8) in a within-subject-crossover design in 28 patients with drug-resistant epilepsy. In order to enable the highest possible adherence, there are no restrictions on the composition of the food.
  arm group label: IF 16:8
  arm group label: IF MCT 16:8
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Wiebke Hahn, MD
  role: Principal Investigator
  affiliation: Philipps University Marburg Medical Center
  last name: Wiebke Hahn, MD
  phone: +49 642158 65348
  email: Hahnwi@staff.uni-marburg.de
  facility: 
  status: Recruiting
  contact: 
  country: Germany
  responsible party type: Principal Investigator
  investigator affiliation: Philipps University Marburg Medical Center
  investigator full name: Susanne Knake
  investigator title: Principal investigator
  mesh term: Epilepsy
  mesh term: Drug Resistant Epilepsy
  sharing ipd: No