<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/NCT03784716</url>
  </required_header>
  <id_info>
    <org_study_id>IIT2018-27-Hussain-KetoLi</org_study_id>
    <nct_id>NCT03784716</nct_id>
  </id_info>
  <brief_title>Ketogenic Diet in Non-alcoholic Fatty Liver Disease</brief_title>
  <official_title>Ke-To Liver Health Study: A Randomized Controlled Trial to Study the Effects of a 28-day Ketogenic Dietary Intervention on Non-alcoholic Fatty Liver Disease Progression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Marc Goodman</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cedars-Sinai Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</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 purpose of this randomized trial is to examine the effects of a ketogenic diet on&#xD;
      non-alcoholic fatty liver disease (NAFLD). Twenty-four participants with NAFLD will be&#xD;
      randomized to receive a ketogenic meal plan or control (standard weight loss meal plan).&#xD;
      Participants will be followed up to 28 days after initiation of the diet intervention.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      We will conduct a randomized trial to examine the effects of a ketogenic diet on&#xD;
      non-alcoholic fatty liver disease (NAFLD). Twenty-four participants with NAFLD will be&#xD;
      randomized into one of two groups: 12 participants will be randomized to receive a ketogenic&#xD;
      meal plan and 12 participants will be randomized to receive a standard weight loss meal plan.&#xD;
      There will be one screening visit and three study visits: the baseline visit, and follow-up&#xD;
      visits 14 days and 28 days after initiation of the diet intervention. The study team&#xD;
      hypothesizes that participants randomized to a ketogenic diet will have a greater reduction&#xD;
      in intrahepatic triglycerides compared to those randomized to a standard weight loss diet.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 13, 2019</start_date>
  <completion_date type="Actual">February 10, 2022</completion_date>
  <primary_completion_date type="Actual">February 10, 2022</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean change in intrahepatic triglyceride content measured by MRI-proton density fat fraction (MRI-PDFF) from baseline to 28 days following diet initiation.</measure>
    <time_frame>28 days</time_frame>
    <description>The MRI-PDFF is a quantitative imaging test that exploits the differences in resonance frequencies between</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean change in liver stiffness measured by magnetic resonance elastography (MRE) from baseline to 28 days following diet initiation.</measure>
    <time_frame>28 days</time_frame>
    <description>Stiffness will be measured by MRE (kPa), a quantitative imaging test that uses sound vibrations to assess the mechanical properties of the liver.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in liver enzyme, aspertate aminotransferase (AST), from baseline to 28 days following diet initiation.</measure>
    <time_frame>28 days</time_frame>
    <description>AST will be measured from blood test at baseline and 28 days from diet initiation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in liver enzyme, Alanine Aminotransferase (ALT), from baseline to 28 days following diet initiation.</measure>
    <time_frame>28 days</time_frame>
    <description>ALT will be measured from blood test at baseline and 28 days from diet initiation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in number of odors correctly identified using 40 microencapsulated odors in the smell identification test (UPSIT) from baseline to 28 days following diet initiation.</measure>
    <time_frame>28 days</time_frame>
    <description>The University of Pennsylvania Smell IdentificationTest (UPSIT) uses 40 microencapsulated odors embedded in questionnaire accompanied by multiple choice questions containing the correct odor.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in perceived sweet taste tested with glucose solutions and a general Labeled Magnitude Scale (gLMS) from baseline to 28 days following diet initiation.</measure>
    <time_frame>28 days</time_frame>
    <description>Sweet taste intensity will be rated on a 100mm general Labeled Magnitude Scale (gLMS) ranging from no sensation (0 mm) to strongest imaginable sensation (100 mm). The mean difference in scores will be calculated at 28 days following diet initiation and baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in patient-reported cognitive function measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) scale from baseline to 28 days following diet initiation.</measure>
    <time_frame>28 days</time_frame>
    <description>Cognitive function will be assessed using the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) short form, which includes 8 items and a range of 1 to 5 (worst outcome). The total score will be calculated and converted into a standardized t-score will be calculated based on a standard population with a mean of 50 and SD of 10.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in patient-reported constipation measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) scale from baseline to 28 days following diet initiation.</measure>
    <time_frame>28 days</time_frame>
    <description>Constipation will be assessed using the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) short form, which includes 9 items and a range of 1 (low constipation) to 5 (high constipation). The total score will be calculated and converted into a standardized t-score will be calculated based on a standard population with a mean of 50 and SD of 10.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in patient-reported fatigue measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) scale from baseline to 28 days following diet initiation.</measure>
    <time_frame>28 days</time_frame>
    <description>Fatigue will be assessed using the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) short form, which includes 8 items and a range of 1 (low fatigue) to 5 (high fatigue). The total score will be calculated and converted into a standardized t-score will be calculated based on a standard population with a mean of 50 and SD of 10.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in physical activity measured by a wearable activity monitor from baseline to 28 days following diet initiation.</measure>
    <time_frame>28 days</time_frame>
    <description>A 7-day average at 28 days will be compared to 7-day baseline activity where at least 4 of 7 days of recorded activity required.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Fatty Liver, Nonalcoholic</condition>
  <condition>Liver Diseases</condition>
  <arm_group>
    <arm_group_label>Ketogenic Diet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ketogenic Diet for 28 Days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard Weight Loss Diet</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard Weight Loss Diet for 28 Days</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Ketogenic Diet</intervention_name>
    <description>Ketogenic diet for 28 days. Meals will be provided to all study participants for 28 days by a prepared meal delivery service. Daily caloric needs for each participant will be determined based on height, weight, gender, age, and activity level. Meals will be prepared based on compliance with the following macronutrient guidelines: 70% fat, 25% protein, and 5% carbohydrate for the ketogenic diet.</description>
    <arm_group_label>Ketogenic Diet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard Weight Loss Diet</intervention_name>
    <description>Standard weight loss diet for 28 days. Meals will be provided to all study participants for 28 days by a prepared meal delivery service. Daily caloric needs for each participant will be determined based on height, weight, gender, age, and activity level. Meals will be prepared based on compliance with the following macronutrient guidelines: 30% fat, 20% protein, and 50% carbohydrate for the standard weight loss diet.</description>
    <arm_group_label>Standard Weight Loss Diet</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age greater than or equal to 18 years at enrollment&#xD;
&#xD;
          -  Diagnosis of NAFLD verified by screening MRI-PDFF greater than or equal to 8%&#xD;
&#xD;
          -  Women able to become pregnant must have a confirmed negative pregnancy test result&#xD;
             prior to enrollment because MRI is contraindicated in pregnant women. Women ≥ 50 years&#xD;
             of age who have not had a menstrual period in the past year; and women who have had a&#xD;
             hysterectomy, both ovaries removed, or a tubal ligation; will not be required to have&#xD;
             a pregnancy test.&#xD;
&#xD;
          -  Women able to become pregnant must agree to use adequate contraception (hormonal or&#xD;
             barrier method of birth control; abstinence) prior to study entry and for the duration&#xD;
             of study participation.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
             and medical release&#xD;
&#xD;
          -  Willing and able to comply with trial protocol and follow-up&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior diagnosis of chronic liver disease other than NAFLD, including autoimmune,&#xD;
             viral, and alcoholic liver disease&#xD;
&#xD;
          -  Prior diagnosis of liver cirrhosis as defined by any of the following criteria:&#xD;
&#xD;
               -  Cirrhosis on historical liver biopsy; or&#xD;
&#xD;
               -  Evidence of cirrhosis on liver imaging (CT, MRI, or US) including a nodular liver&#xD;
                  surface, splenomegaly, or portal venous collaterals; or&#xD;
&#xD;
               -  Prior history of decompensated liver disease, including ascites, hepatic&#xD;
                  encephalopathy, or variceal bleeding; or&#xD;
&#xD;
               -  FibroScan value of &gt;14.9 kPa; or&#xD;
&#xD;
               -  MRE of 4.67 kPa or higher&#xD;
&#xD;
          -  History of liver transplantation&#xD;
&#xD;
          -  Body mass index (BMI) less than 27 kg/m&#xD;
&#xD;
          -  Unstable body weight (&gt; 10% change in prior 3 months)&#xD;
&#xD;
          -  Prior weight reduction surgery within the last 5 years&#xD;
&#xD;
          -  Use of a medication prescribed for weight loss within the past 3 months&#xD;
&#xD;
          -  Current alcohol consumption &gt;21 oz. per week for males or &gt;14 oz. per week for females&#xD;
             (1 oz./30 mL of alcohol is present in one 12 oz./360 mL beer, one 4 oz./120 mL glass&#xD;
             of wine, and one 1 oz./30 mL measure of 40% proof alcohol)&#xD;
&#xD;
          -  Unstable cardiovascular disease as defined by any of the following:&#xD;
&#xD;
               -  Unstable angina within 6 months prior to screening&#xD;
&#xD;
               -  Myocardial infarction, coronary artery bypass graft surgery or coronary&#xD;
                  angioplasty within 6 months prior to screening&#xD;
&#xD;
               -  Transient ischemic attack or cerebrovascular accident within 6 months prior to&#xD;
                  screening&#xD;
&#xD;
               -  Obstructive valvular heart disease or hypertrophic cardiomyopathy&#xD;
&#xD;
               -  Unstable congestive heart failure&#xD;
&#xD;
          -  Women who are pregnant or breastfeeding or are implanted with intrauterine devices&#xD;
             that are not MRI-compatible&#xD;
&#xD;
          -  Active malignancy within the past 5 years (excluding basal/squamous cell skin cancer,&#xD;
             or prostate cancer with a Gleason score 6 or less)&#xD;
&#xD;
          -  Known HIV infection&#xD;
&#xD;
          -  Food allergies or dietary restrictions, including vegan or vegetarian diet, which&#xD;
             cannot be accommodated with the prepared meal service&#xD;
&#xD;
          -  Contraindication to undergo MRI-PDFF or MRE, including persons with mechanically,&#xD;
             magnetically, or electrically activated implants, such as cardiac pacemakers or&#xD;
             defibrillators, or infusion pumps; or ferromagnetic implants or foreign bodies, such&#xD;
             as aneurysm clips or shrapnel; or other implanted electronic devices or metallic parts&#xD;
             in the body prohibiting MRI. Because the MRI scanner is also used with animals,&#xD;
             persons with allergy to animal dander or animal-instigated asthma are also excluded.&#xD;
&#xD;
          -  Resides outside of the meal delivery zone or plans to travel outside of the meal&#xD;
             delivery zone for more than one day while on the study intervention and will be unable&#xD;
             to access the meal delivery&#xD;
&#xD;
          -  Current use of any investigational agents&#xD;
&#xD;
          -  Concurrent illness or abnormal laboratory result which in the opinion of the&#xD;
             investigators would compromise either the patient or the integrity of the data&#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>Marc Goodman, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cedars-Sinai Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cedars-Sinai Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>December 4, 2018</study_first_submitted>
  <study_first_submitted_qc>December 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 24, 2018</study_first_posted>
  <last_update_submitted>May 10, 2022</last_update_submitted>
  <last_update_submitted_qc>May 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 11, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Cedars-Sinai Medical Center</investigator_affiliation>
    <investigator_full_name>Marc Goodman</investigator_full_name>
    <investigator_title>Principal Investigator; Director Cancer Prevention and Control; Professor, Department Cancer Institute</investigator_title>
  </responsible_party>
  <keyword>Fatty Liver</keyword>
  <keyword>Liver Disease</keyword>
  <keyword>Ketogenic diet</keyword>
  <keyword>Keto diet</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
    <mesh_term>Fatty Liver</mesh_term>
    <mesh_term>Non-alcoholic Fatty Liver Disease</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/NCT03784716
org study id: IIT2018-27-Hussain-KetoLi
nct id: NCT03784716
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this randomized trial is to examine the effects of a ketogenic diet on
      non-alcoholic fatty liver disease (NAFLD). Twenty-four participants with NAFLD will be
      randomized to receive a ketogenic meal plan or control (standard weight loss meal plan).
      Participants will be followed up to 28 days after initiation of the diet intervention.
We will conduct a randomized trial to examine the effects of a ketogenic diet on
      non-alcoholic fatty liver disease (NAFLD). Twenty-four participants with NAFLD will be
      randomized into one of two groups: 12 participants will be randomized to receive a ketogenic
      meal plan and 12 participants will be randomized to receive a standard weight loss meal plan.
      There will be one screening visit and three study visits: the baseline visit, and follow-up
      visits 14 days and 28 days after initiation of the diet intervention. The study team
      hypothesizes that participants randomized to a ketogenic diet will have a greater reduction
      in intrahepatic triglycerides compared to those randomized to a standard weight loss diet.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Mean change in intrahepatic triglyceride content measured by MRI-proton density fat fraction (MRI-PDFF) from baseline to 28 days following diet initiation.
time frame: 28 days
description: The MRI-PDFF is a quantitative imaging test that exploits the differences in resonance frequencies between
measure: Mean change in liver stiffness measured by magnetic resonance elastography (MRE) from baseline to 28 days following diet initiation.
time frame: 28 days
description: Stiffness will be measured by MRE (kPa), a quantitative imaging test that uses sound vibrations to assess the mechanical properties of the liver.
measure: Mean change in liver enzyme, aspertate aminotransferase (AST), from baseline to 28 days following diet initiation.
time frame: 28 days
description: AST will be measured from blood test at baseline and 28 days from diet initiation
measure: Mean change in liver enzyme, Alanine Aminotransferase (ALT), from baseline to 28 days following diet initiation.
time frame: 28 days
description: ALT will be measured from blood test at baseline and 28 days from diet initiation
measure: Mean change in number of odors correctly identified using 40 microencapsulated odors in the smell identification test (UPSIT) from baseline to 28 days following diet initiation.
time frame: 28 days
description: The University of Pennsylvania Smell IdentificationTest (UPSIT) uses 40 microencapsulated odors embedded in questionnaire accompanied by multiple choice questions containing the correct odor.
measure: Mean change in perceived sweet taste tested with glucose solutions and a general Labeled Magnitude Scale (gLMS) from baseline to 28 days following diet initiation.
time frame: 28 days
description: Sweet taste intensity will be rated on a 100mm general Labeled Magnitude Scale (gLMS) ranging from no sensation (0 mm) to strongest imaginable sensation (100 mm). The mean difference in scores will be calculated at 28 days following diet initiation and baseline.
measure: Mean change in patient-reported cognitive function measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) scale from baseline to 28 days following diet initiation.
time frame: 28 days
description: Cognitive function will be assessed using the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) short form, which includes 8 items and a range of 1 to 5 (worst outcome). The total score will be calculated and converted into a standardized t-score will be calculated based on a standard population with a mean of 50 and SD of 10.
measure: Mean change in patient-reported constipation measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) scale from baseline to 28 days following diet initiation.
time frame: 28 days
description: Constipation will be assessed using the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) short form, which includes 9 items and a range of 1 (low constipation) to 5 (high constipation). The total score will be calculated and converted into a standardized t-score will be calculated based on a standard population with a mean of 50 and SD of 10.
measure: Mean change in patient-reported fatigue measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) scale from baseline to 28 days following diet initiation.
time frame: 28 days
description: Fatigue will be assessed using the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) short form, which includes 8 items and a range of 1 (low fatigue) to 5 (high fatigue). The total score will be calculated and converted into a standardized t-score will be calculated based on a standard population with a mean of 50 and SD of 10.
measure: Mean change in physical activity measured by a wearable activity monitor from baseline to 28 days following diet initiation.
time frame: 28 days
description: A 7-day average at 28 days will be compared to 7-day baseline activity where at least 4 of 7 days of recorded activity required.
arm group label: Ketogenic Diet
arm group type: Experimental
description: Ketogenic Diet for 28 Days
arm group label: Standard Weight Loss Diet
arm group type: Active Comparator
description: Standard Weight Loss Diet for 28 Days
intervention type: Other
intervention name: Ketogenic Diet
description: Ketogenic diet for 28 days. Meals will be provided to all study participants for 28 days by a prepared meal delivery service. Daily caloric needs for each participant will be determined based on height, weight, gender, age, and activity level. Meals will be prepared based on compliance with the following macronutrient guidelines: 70% fat, 25% protein, and 5% carbohydrate for the ketogenic diet.
arm group label: Ketogenic Diet
intervention type: Other
intervention name: Standard Weight Loss Diet
description: Standard weight loss diet for 28 days. Meals will be provided to all study participants for 28 days by a prepared meal delivery service. Daily caloric needs for each participant will be determined based on height, weight, gender, age, and activity level. Meals will be prepared based on compliance with the following macronutrient guidelines: 30% fat, 20% protein, and 50% carbohydrate for the standard weight loss diet.
arm group label: Standard Weight Loss Diet
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marc Goodman, PhD
role: Principal Investigator
affiliation: Cedars-Sinai Medical Center
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Cedars-Sinai Medical Center
investigator full name: Marc Goodman
investigator title: Principal Investigator; Director Cancer Prevention and Control; Professor, Department Cancer Institute
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease