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/NCT06000774</url>
    </required_header>
    <id_info>
      <org_study_id>807674</org_study_id>
      <nct_id>NCT06000774</nct_id>
    </id_info>
    <brief_title>Therapeutic Ketogenic Diet in Anorexia Nervosa</brief_title>
    <official_title>Ketogenic Diet in Weight Recovered Anorexia Nervosa to Target Metabolism and Normalize Persistent Eating Disorder Psychopathology</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of California, San Diego</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of California, San Diego</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>
        This study will investigate the effects of therapeutic ketogenic diet (TKD) on eating&#xD;
        behavior including drive to restrict, body dissatisfaction, mood and anxiety in individuals&#xD;
        with anorexia nervosa who have been weight normalized (body mass index of 17.5 or greater)&#xD;
        but continue to struggle with eating disorder behaviors including a high drive for thinness&#xD;
        and body dissatisfaction.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        For this 14-week study, the investigator will recruit twenty individuals with anorexia&#xD;
        nervosa who have been weight normalized but continue to have high impairment from the illness&#xD;
        with a high (2 standard deviations above average) drive for thinness and body dissatisfaction&#xD;
        and a high drive for food restriction and thus are at high risk for full relapse. Study&#xD;
        participants will be carefully assessed and oriented to the ketogenic diet according to the&#xD;
        procedures in our small previous trial (Calabrese, et al., 2022). The study will be conducted&#xD;
        in a university medical environment, showing feasibility and safety in a typical medical&#xD;
        setting. A commercial supplier will provide the ketogenic diet. After ketosis induction over&#xD;
        two weeks, study participants will be assessed weekly for ketosis and mood, anxiety, and&#xD;
        eating disorder symptoms.&#xD;
  &#xD;
        Primary Objective 1 is to test the effects of ketogenic diet in individuals with anorexia&#xD;
        nervosa who are weight recovered but continue to suffer severely from drive for thinness and&#xD;
        are at very high relapse risk. Participants will be evaluated for tolerability of the study&#xD;
        and weight trajectory. Primary Objective 2 is to assess improvement in AN symptoms and&#xD;
        behaviors in relation to the ketogenic diet over a 12-week course. Participants will be&#xD;
        assessed for specific symptoms such as drive for thinness and body dissatisfaction, fear of&#xD;
        eating and weight gain. Primary Objective 3 is to assess the underlying genetic basis for the&#xD;
        treatment effect of the ketogenic diet.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">September 6, 2023</start_date>
    <completion_date type="Anticipated">March 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">September 30, 2024</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>Subjects will complete a 14-week therapeutic ketogenic diet (TKD)</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>To assess the safety and tolerability in individuals with anorexia nervosa who are weight recovered using weekly body weight measurements.</measure>
      <time_frame>Weekly for the duration of the study intervention (14 weeks)</time_frame>
      <description>Weekly weights will be obtained to assess whether subjects remain within a normal weight range.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>To assess the safety and tolerability in individuals with anorexia nervosa who are weight recovered using the Committee of Clinical Investigations UKU-Side Effect Scale</measure>
      <time_frame>At weeks 4, 8, 12, 14</time_frame>
      <description>The UKU assesses psychiatric, neurologic, autonomic, and other side effects.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Measurement of drive for weight loss, fear of weight gain and body image distortion using the Eating Disorder Examination Questionnaire (EDEQ) Global Score, EDEQ Eating Restraint Score, and EDEQ Weight Concern</measure>
      <time_frame>At baseline, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 3 month follow-up</time_frame>
      <description>The Eating Disorders Examination Questionnaire a self report assessment that measures core eating disorder symptoms. Subjects will complete this measure at the beginning and end of the study and weekly throughout the 14-week intervention and the investigator will measure the change in scores. The EDE Global, Eating Restraint, and Weight Concern scales have a range of 0 to 6 where higher scores mean worse outcome.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Measurement of the relationship between genotype and improvement of eating disorder symptoms</measure>
      <time_frame>At baseline</time_frame>
      <description>In order to identify potential genetic signatures that may predict response to treatment, Whole Exome Sequencing will be conducted on participants.</description>
    </primary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Anorexia Nervosa in Remission</condition>
    <arm_group>
      <arm_group_label>Therapeutic Ketogenic Diet</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>A 2-week therapeutic ketogenic diet (TKD) induction will be implemented to establish nutritional ketosis (the goal are BHB blood levels of 0.5-3.0 millimoles per liter [mmol/L]). After establishing the ketotic state, study participants will continue TKD for 12 weeks.</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Therapeutic Ketogenic Diet</intervention_name>
      <description>therapeutic ketogenic diet</description>
      <arm_group_label>Therapeutic Ketogenic Diet</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Provision of signed and dated informed consent form&#xD;
  &#xD;
            2. Stated willingness to comply with all study procedures and availability for the&#xD;
               duration of the study&#xD;
  &#xD;
            3. Persons, aged 18 to 45 years&#xD;
  &#xD;
            4. History of anorexia nervosa according to DSM-5 criteria&#xD;
  &#xD;
            5. Weight recovered at the time of study inclusion (body mass index &gt; 17.5 kg/m2)&#xD;
  &#xD;
            6. Greater or equal to 2 standard deviations scores of eating disorder-relevant behaviors&#xD;
               on the Eating Disorder Inventory-3 and Eating Disorder Examination Questionnaire&#xD;
  &#xD;
            7. The following types of psychiatric medications are allowed: antidepressant,&#xD;
               anxiolytic, atypical antipsychotic, mood stabilizers&#xD;
  &#xD;
            8. English is primary spoken language&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Pregnancy or lactation&#xD;
  &#xD;
            2. Electrolyte, blood count, kidney function or liver function abnormalities&#xD;
  &#xD;
            3. Psychosis&#xD;
  &#xD;
            4. Neurocognitive disorders including dementias or traumatic brain injury that is&#xD;
               symptomatic&#xD;
  &#xD;
            5. Current alcohol use disorder (AUD) or substance use disorder (SUD) according to DSM-5&#xD;
               criteria&#xD;
  &#xD;
            6. Uncontrolled hypertension&#xD;
  &#xD;
            7. Hepatic impairment (Class-Pugh b or c)&#xD;
  &#xD;
            8. Diabetes mellitus&#xD;
  &#xD;
            9. Family history of porphyria&#xD;
  &#xD;
           10. History of recent heart attack, vascular disease, or any other current acute medical&#xD;
               conditions as determined by the principal investigator&#xD;
  &#xD;
           11. Inability or unwillingness to adhere to the TKD diet for the duration of the study&#xD;
  &#xD;
           12. Blind or illiterate individuals&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>45 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Guido Frank, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of California, San Diego</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Megan Shott, BS</last_name>
      <phone>848-246-5272</phone>
      <email>mshott@health.ucsd.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>University of California San Diego</name>
        <address>
          <city>San Diego</city>
          <state>California</state>
          <zip>92121</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Megan E Shott, BS</last_name>
        <phone>858-246-5272</phone>
        <email>mshott@health.ucsd.edu</email>
      </contact>
      <contact_backup>
        <last_name>Guido Frank, MD</last_name>
        <email>gfrank@health.ucsd.edu</email>
      </contact_backup>
      <investigator>
        <last_name>Guido Frank, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <reference>
      <citation>Scolnick B, Zupec-Kania B, Calabrese L, Aoki C, Hildebrandt T. Remission from Chronic Anorexia Nervosa With Ketogenic Diet and Ketamine: Case Report. Front Psychiatry. 2020 Jul 30;11:763. doi: 10.3389/fpsyt.2020.00763. eCollection 2020.</citation>
      <PMID>32848935</PMID>
    </reference>
    <reference>
      <citation>Frank GKW, Shott ME, DeGuzman MC. The Neurobiology of Eating Disorders. Child Adolesc Psychiatr Clin N Am. 2019 Oct;28(4):629-640. doi: 10.1016/j.chc.2019.05.007. Epub 2019 Jul 4.</citation>
      <PMID>31443880</PMID>
    </reference>
    <reference>
      <citation>Frank GKW, Shott ME, Stoddard J, Swindle S, Pryor TL. Association of Brain Reward Response With Body Mass Index and Ventral Striatal-Hypothalamic Circuitry Among Young Women With Eating Disorders. JAMA Psychiatry. 2021 Oct 1;78(10):1123-1133. doi: 10.1001/jamapsychiatry.2021.1580.</citation>
      <PMID>34190963</PMID>
    </reference>
    <reference>
      <citation>Dignon A, Beardsmore A, Spain S, Kuan A. 'Why I won't eat': patient testimony from 15 anorexics concerning the causes of their disorder. J Health Psychol. 2006 Nov;11(6):942-56. doi: 10.1177/1359105306069097.</citation>
      <PMID>17035265</PMID>
    </reference>
    <reference>
      <citation>Calabrese L, Scolnick B, Zupec-Kania B, Beckwith C, Costello K, Frank GKW. Ketogenic diet and ketamine infusion treatment to target chronic persistent eating disorder psychopathology in anorexia nervosa: a pilot study. Eat Weight Disord. 2022 Dec;27(8):3751-3757. doi: 10.1007/s40519-022-01455-x. Epub 2022 Aug 23.</citation>
      <PMID>35997954</PMID>
    </reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 14, 2023</study_first_submitted>
    <study_first_submitted_qc>August 14, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>September 6, 2023</last_update_submitted>
    <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of California, San Diego</investigator_affiliation>
      <investigator_full_name>Guido Frank</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Anorexia</mesh_term>
      <mesh_term>Anorexia Nervosa</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/NCT06000774
  org study id: 807674
  nct id: NCT06000774
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This study will investigate the effects of therapeutic ketogenic diet (TKD) on eating
        behavior including drive to restrict, body dissatisfaction, mood and anxiety in individuals
        with anorexia nervosa who have been weight normalized (body mass index of 17.5 or greater)
        but continue to struggle with eating disorder behaviors including a high drive for thinness
        and body dissatisfaction.
  For this 14-week study, the investigator will recruit twenty individuals with anorexia
        nervosa who have been weight normalized but continue to have high impairment from the illness
        with a high (2 standard deviations above average) drive for thinness and body dissatisfaction
        and a high drive for food restriction and thus are at high risk for full relapse. Study
        participants will be carefully assessed and oriented to the ketogenic diet according to the
        procedures in our small previous trial (Calabrese, et al., 2022). The study will be conducted
        in a university medical environment, showing feasibility and safety in a typical medical
        setting. A commercial supplier will provide the ketogenic diet. After ketosis induction over
        two weeks, study participants will be assessed weekly for ketosis and mood, anxiety, and
        eating disorder symptoms.
  
        Primary Objective 1 is to test the effects of ketogenic diet in individuals with anorexia
        nervosa who are weight recovered but continue to suffer severely from drive for thinness and
        are at very high relapse risk. Participants will be evaluated for tolerability of the study
        and weight trajectory. Primary Objective 2 is to assess improvement in AN symptoms and
        behaviors in relation to the ketogenic diet over a 12-week course. Participants will be
        assessed for specific symptoms such as drive for thinness and body dissatisfaction, fear of
        eating and weight gain. Primary Objective 3 is to assess the underlying genetic basis for the
        treatment effect of the ketogenic diet.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: Subjects will complete a 14-week therapeutic ketogenic diet (TKD)
  primary purpose: Treatment
  masking: None (Open Label)
  measure: To assess the safety and tolerability in individuals with anorexia nervosa who are weight recovered using weekly body weight measurements.
  time frame: Weekly for the duration of the study intervention (14 weeks)
  description: Weekly weights will be obtained to assess whether subjects remain within a normal weight range.
  measure: To assess the safety and tolerability in individuals with anorexia nervosa who are weight recovered using the Committee of Clinical Investigations UKU-Side Effect Scale
  time frame: At weeks 4, 8, 12, 14
  description: The UKU assesses psychiatric, neurologic, autonomic, and other side effects.
  measure: Measurement of drive for weight loss, fear of weight gain and body image distortion using the Eating Disorder Examination Questionnaire (EDEQ) Global Score, EDEQ Eating Restraint Score, and EDEQ Weight Concern
  time frame: At baseline, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 3 month follow-up
  description: The Eating Disorders Examination Questionnaire a self report assessment that measures core eating disorder symptoms. Subjects will complete this measure at the beginning and end of the study and weekly throughout the 14-week intervention and the investigator will measure the change in scores. The EDE Global, Eating Restraint, and Weight Concern scales have a range of 0 to 6 where higher scores mean worse outcome.
  measure: Measurement of the relationship between genotype and improvement of eating disorder symptoms
  time frame: At baseline
  description: In order to identify potential genetic signatures that may predict response to treatment, Whole Exome Sequencing will be conducted on participants.
  arm group label: Therapeutic Ketogenic Diet
  arm group type: Experimental
  description: A 2-week therapeutic ketogenic diet (TKD) induction will be implemented to establish nutritional ketosis (the goal are BHB blood levels of 0.5-3.0 millimoles per liter [mmol/L]). After establishing the ketotic state, study participants will continue TKD for 12 weeks.
  intervention type: Other
  intervention name: Therapeutic Ketogenic Diet
  description: therapeutic ketogenic diet
  arm group label: Therapeutic Ketogenic Diet
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 45 Years
  healthy volunteers: No
  last name: Guido Frank, MD
  role: Principal Investigator
  affiliation: University of California, San Diego
  last name: Megan Shott, BS
  phone: 848-246-5272
  email: mshott@health.ucsd.edu
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  country: United States
  citation: Scolnick B, Zupec-Kania B, Calabrese L, Aoki C, Hildebrandt T. Remission from Chronic Anorexia Nervosa With Ketogenic Diet and Ketamine: Case Report. Front Psychiatry. 2020 Jul 30;11:763. doi: 10.3389/fpsyt.2020.00763. eCollection 2020.
  PMID: 32848935
  citation: Frank GKW, Shott ME, DeGuzman MC. The Neurobiology of Eating Disorders. Child Adolesc Psychiatr Clin N Am. 2019 Oct;28(4):629-640. doi: 10.1016/j.chc.2019.05.007. Epub 2019 Jul 4.
  PMID: 31443880
  citation: Frank GKW, Shott ME, Stoddard J, Swindle S, Pryor TL. Association of Brain Reward Response With Body Mass Index and Ventral Striatal-Hypothalamic Circuitry Among Young Women With Eating Disorders. JAMA Psychiatry. 2021 Oct 1;78(10):1123-1133. doi: 10.1001/jamapsychiatry.2021.1580.
  PMID: 34190963
  citation: Dignon A, Beardsmore A, Spain S, Kuan A. 'Why I won't eat': patient testimony from 15 anorexics concerning the causes of their disorder. J Health Psychol. 2006 Nov;11(6):942-56. doi: 10.1177/1359105306069097.
  PMID: 17035265
  citation: Calabrese L, Scolnick B, Zupec-Kania B, Beckwith C, Costello K, Frank GKW. Ketogenic diet and ketamine infusion treatment to target chronic persistent eating disorder psychopathology in anorexia nervosa: a pilot study. Eat Weight Disord. 2022 Dec;27(8):3751-3757. doi: 10.1007/s40519-022-01455-x. Epub 2022 Aug 23.
  PMID: 35997954
  responsible party type: Principal Investigator
  investigator affiliation: University of California, San Diego
  investigator full name: Guido Frank
  investigator title: Professor
  mesh term: Anorexia
  mesh term: Anorexia Nervosa
  sharing ipd: No