<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/NCT04450875</url>
  </required_header>
  <id_info>
    <org_study_id>ISP-CI-003/2014</org_study_id>
    <secondary_id>001/060/0194</secondary_id>
    <nct_id>NCT04450875</nct_id>
  </id_info>
  <brief_title>Efficacy of Nutritional Therapy With High Methionine Content in the Treatment of NAFLD</brief_title>
  <official_title>Efficacy of Nutritional Therapy With High Methionine Content in the Treatment of Non-alcoholic Fatty Liver: a Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universidad Veracruzana</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Council of Science and Technology, Mexico</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universidad Veracruzana</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>
      To assess the effect of a methionine metabolism-based dietary strategy in patients with&#xD;
      non-alcoholic fatty liver disease in order to reduce complications while improving the&#xD;
      quality of life for patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A randomized controlled clinical trial with parallel design was performed, a ratio of at&#xD;
      least one patient in the control group for each subject in the experimental group.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 24, 2015</start_date>
  <completion_date type="Actual">November 1, 2017</completion_date>
  <primary_completion_date type="Actual">February 1, 2016</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>
    <intervention_model_description>Experimental group: It consisted of a nutritional therapy administration of foods with a high content of methionine according to the National Nutrient Database For Standard Reference (USDA) and adapted to the consumption and usual cost in the Mexican diet. The supervision of the nutritional therapy was carried out through 24-hour reminders, where each patient wrote down the amount and food consumed described in the diet during a 3-month follow-up period. Because the daily requirement for methionine for adults is 260 to 700 mg 98, patients were instructed to combine the foods until they reached a daily intake of at least 700 mg of methionine. Two nutritionists performed both diet instruction and 24-hour reminder monitoring monthly. At the end of the three-month follow-up, the 24-hour reminder data such as food consumed, daily rations, and the monthly average of milligrams of consumed methionine contained in the food, were recorded in a database for subsequent analysis.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>Balanced groups are produced on the computer-generated random numbers based on the sex of the study subjects, that is, men and women were proportionally assigned in both groups. An investigator from outside the allocation of exposure generated the random numbers in four blocks: 1) men assigned to the experimental group, 2) women assigned to the experimental group, 3) men assigned to the control group and 4) women assigned to the control group. A second investigator, blindly assigned subjects to experimental and control group. Although concealment of allocation to interest groups could be confirmed, masking of difficulties was not possible once the follow-up began.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>NAFLD reversal</measure>
    <time_frame>Three months</time_frame>
    <description>Change in FLI to a level less than 60 points at the end of the dietary intervention. FLI was the result of the algorithm based on waist circumference, body mass index, serum GGT level and triglycerides. Bedogni, et al developed this fatty liver prediction model. The total possible score ranges from 1 to 100 points, where a score greater than or equal to 60 is considered to be NAFLD probable, and a level below 30 points is considered normal</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Short Form (36) Health Survey (SF-36).</measure>
    <time_frame>Three months</time_frame>
    <description>The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. .This questionnaire has been adapted to the Mexican population</description>
  </secondary_outcome>
  <other_outcome>
    <measure>ALT (Level of liver damage enzymes)</measure>
    <time_frame>Three months</time_frame>
    <description>Alanine aminotransferase (ALT) High levels (&gt;50) indicate damage to liver cells. It will be expressed as mean and standard deviation and will be compared in both groups.</description>
  </other_outcome>
  <other_outcome>
    <measure>AST (Level of liver damage enzymes)</measure>
    <time_frame>Three months</time_frame>
    <description>A high result on an AST test might indicate a problem with the liver or muscles. It will be expressed as mean and standard deviation and will be compared in both groups.&#xD;
The normal range for AST is typically up to 40 IU/L</description>
  </other_outcome>
  <other_outcome>
    <measure>GGT(Level of liver damage enzymes)</measure>
    <time_frame>Three months</time_frame>
    <description>High levels of GGT in the blood could indicate that the enzyme is leaking out of the liver cells and into the blood, suggesting damage to the liver or bile ducts. A typical range for GGT levels in adults is between 0 and 30 international units per liter (IU/L). It will be expressed as mean and standard deviation and will be compared in both groups.</description>
  </other_outcome>
  <other_outcome>
    <measure>Glucose</measure>
    <time_frame>Three months</time_frame>
    <description>Elevated fasting glucose ≥ 100 mg/dl. It will be expressed as mean and standard deviation and will be compared in both groups.</description>
  </other_outcome>
  <other_outcome>
    <measure>Triglycerides</measure>
    <time_frame>Three months</time_frame>
    <description>Elevated triglycerides ≥150 mg/dL (1.7 mmol/L). It will be expressed as mean and standard deviation and will be compared in both groups.</description>
  </other_outcome>
  <other_outcome>
    <measure>Cholesterol</measure>
    <time_frame>Three months</time_frame>
    <description>Reduced HDL colesterol &lt;40 mg/dL (1.03 mmol/L) in men &lt;50 mg/dL (1.3 mmol/L) in women. It will be expressed as mean and standard deviation and will be compared in both groups.</description>
  </other_outcome>
  <other_outcome>
    <measure>Weight</measure>
    <time_frame>Three months</time_frame>
    <description>Measurement in kilograms</description>
  </other_outcome>
  <other_outcome>
    <measure>Height Height</measure>
    <time_frame>Three months</time_frame>
    <description>Measurement in meters</description>
  </other_outcome>
  <other_outcome>
    <measure>Body mass index (BMI)</measure>
    <time_frame>Three months</time_frame>
    <description>Weight and height will be combined to report BMI in kg/m^2. It will be expressed as mean and standard deviation and will be compared in both groups.</description>
  </other_outcome>
  <other_outcome>
    <measure>Waist</measure>
    <time_frame>Three months</time_frame>
    <description>Measurement in centimeters</description>
  </other_outcome>
  <other_outcome>
    <measure>Hip</measure>
    <time_frame>Three months</time_frame>
    <description>Measurement in centimeters</description>
  </other_outcome>
  <other_outcome>
    <measure>Waist-hip ratio</measure>
    <time_frame>Three months</time_frame>
    <description>Wast and hip will be combined to report WHR in cm. It will be expressed as mean and standard deviation and will be compared in both groups.</description>
  </other_outcome>
  <other_outcome>
    <measure>Systolic BP</measure>
    <time_frame>Three months</time_frame>
    <description>Report SBP in mmHg, will be assessed during the study period</description>
  </other_outcome>
  <other_outcome>
    <measure>Diastolic BP</measure>
    <time_frame>Three months</time_frame>
    <description>Report DBP in mmHg, will be assessed during the study period</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">121</enrollment>
  <condition>Non-alcoholic Fatty Liver Disease (NAFLD)</condition>
  <arm_group>
    <arm_group_label>Experimental group (with diet)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>It consisted in the administration of nutritional therapy with foods high in methionine according to the National Nutrient Database For Standard Reference (USDA) and adapted to the consumption and usual cost in the Mexican diet.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>The control group continued with their usual diet for the same period of 3 months as the experimental group.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Experimental group (with diet)</intervention_name>
    <description>Two nutritionists performed both diet instruction and 24-hour reminder monitoring monthly. At the end of the three-month follow-up, the 24-hour reminder data such as food consumed, daily rations, and the monthly average of milligrams of consumed methionine contained in the food, were recorded in a database for subsequent analysis.</description>
    <arm_group_label>Experimental group (with diet)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        • Diagnosis of Non-alcoholic Fatty Liver Disease by biochemical parameters used by the&#xD;
        SteatoTest and Fatty Liver Index (IHG), greater than 60 points on the scale and confirmed&#xD;
        by liver ultrasound&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        • Previous diagnosis of cirrhosis, hepatocarcinoma, Wilson's disease, viral hepatitis B and&#xD;
        C and neoplasms of any origin&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Balanced groups were produced based on the sex of the study subjects, that is, men and women were proportionally assigned in both groups.</gender_description>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rebeca García Román, PHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UV</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rebeca García Román</name>
      <address>
        <city>Xalapa</city>
        <state>Veracruz</state>
        <zip>91190</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Mexico</country>
  </location_countries>
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  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 19, 2020</study_first_submitted>
  <study_first_submitted_qc>June 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 30, 2020</study_first_posted>
  <last_update_submitted>June 24, 2020</last_update_submitted>
  <last_update_submitted_qc>June 24, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universidad Veracruzana</investigator_affiliation>
    <investigator_full_name>María Cristina León</investigator_full_name>
    <investigator_title>Investigator</investigator_title>
  </responsible_party>
  <keyword>Non-alcoholic Fatty Liver Disease</keyword>
  <keyword>Nutrition Therapy</keyword>
  <keyword>Randomized Controlled Trials</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>
  <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/NCT04450875
org study id: ISP-CI-003/2014
secondary id: 001/060/0194
nct id: NCT04450875
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
To assess the effect of a methionine metabolism-based dietary strategy in patients with
      non-alcoholic fatty liver disease in order to reduce complications while improving the
      quality of life for patients.
A randomized controlled clinical trial with parallel design was performed, a ratio of at
      least one patient in the control group for each subject in the experimental group.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Experimental group: It consisted of a nutritional therapy administration of foods with a high content of methionine according to the National Nutrient Database For Standard Reference (USDA) and adapted to the consumption and usual cost in the Mexican diet. The supervision of the nutritional therapy was carried out through 24-hour reminders, where each patient wrote down the amount and food consumed described in the diet during a 3-month follow-up period. Because the daily requirement for methionine for adults is 260 to 700 mg 98, patients were instructed to combine the foods until they reached a daily intake of at least 700 mg of methionine. Two nutritionists performed both diet instruction and 24-hour reminder monitoring monthly. At the end of the three-month follow-up, the 24-hour reminder data such as food consumed, daily rations, and the monthly average of milligrams of consumed methionine contained in the food, were recorded in a database for subsequent analysis.
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
masking description: Balanced groups are produced on the computer-generated random numbers based on the sex of the study subjects, that is, men and women were proportionally assigned in both groups. An investigator from outside the allocation of exposure generated the random numbers in four blocks: 1) men assigned to the experimental group, 2) women assigned to the experimental group, 3) men assigned to the control group and 4) women assigned to the control group. A second investigator, blindly assigned subjects to experimental and control group. Although concealment of allocation to interest groups could be confirmed, masking of difficulties was not possible once the follow-up began.
measure: NAFLD reversal
time frame: Three months
description: Change in FLI to a level less than 60 points at the end of the dietary intervention. FLI was the result of the algorithm based on waist circumference, body mass index, serum GGT level and triglycerides. Bedogni, et al developed this fatty liver prediction model. The total possible score ranges from 1 to 100 points, where a score greater than or equal to 60 is considered to be NAFLD probable, and a level below 30 points is considered normal
measure: The Short Form (36) Health Survey (SF-36).
time frame: Three months
description: The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. .This questionnaire has been adapted to the Mexican population
measure: ALT (Level of liver damage enzymes)
time frame: Three months
description: Alanine aminotransferase (ALT) High levels (>50) indicate damage to liver cells. It will be expressed as mean and standard deviation and will be compared in both groups.
measure: AST (Level of liver damage enzymes)
time frame: Three months
description: A high result on an AST test might indicate a problem with the liver or muscles. It will be expressed as mean and standard deviation and will be compared in both groups.
The normal range for AST is typically up to 40 IU/L
measure: GGT(Level of liver damage enzymes)
time frame: Three months
description: High levels of GGT in the blood could indicate that the enzyme is leaking out of the liver cells and into the blood, suggesting damage to the liver or bile ducts. A typical range for GGT levels in adults is between 0 and 30 international units per liter (IU/L). It will be expressed as mean and standard deviation and will be compared in both groups.
measure: Glucose
time frame: Three months
description: Elevated fasting glucose ≥ 100 mg/dl. It will be expressed as mean and standard deviation and will be compared in both groups.
measure: Triglycerides
time frame: Three months
description: Elevated triglycerides ≥150 mg/dL (1.7 mmol/L). It will be expressed as mean and standard deviation and will be compared in both groups.
measure: Cholesterol
time frame: Three months
description: Reduced HDL colesterol <40 mg/dL (1.03 mmol/L) in men <50 mg/dL (1.3 mmol/L) in women. It will be expressed as mean and standard deviation and will be compared in both groups.
measure: Weight
time frame: Three months
description: Measurement in kilograms
measure: Height Height
time frame: Three months
description: Measurement in meters
measure: Body mass index (BMI)
time frame: Three months
description: Weight and height will be combined to report BMI in kg/m^2. It will be expressed as mean and standard deviation and will be compared in both groups.
measure: Waist
time frame: Three months
description: Measurement in centimeters
measure: Hip
time frame: Three months
description: Measurement in centimeters
measure: Waist-hip ratio
time frame: Three months
description: Wast and hip will be combined to report WHR in cm. It will be expressed as mean and standard deviation and will be compared in both groups.
measure: Systolic BP
time frame: Three months
description: Report SBP in mmHg, will be assessed during the study period
measure: Diastolic BP
time frame: Three months
description: Report DBP in mmHg, will be assessed during the study period
arm group label: Experimental group (with diet)
arm group type: Experimental
description: It consisted in the administration of nutritional therapy with foods high in methionine according to the National Nutrient Database For Standard Reference (USDA) and adapted to the consumption and usual cost in the Mexican diet.
arm group label: Control
arm group type: No Intervention
description: The control group continued with their usual diet for the same period of 3 months as the experimental group.
intervention type: Dietary Supplement
intervention name: Experimental group (with diet)
description: Two nutritionists performed both diet instruction and 24-hour reminder monitoring monthly. At the end of the three-month follow-up, the 24-hour reminder data such as food consumed, daily rations, and the monthly average of milligrams of consumed methionine contained in the food, were recorded in a database for subsequent analysis.
arm group label: Experimental group (with diet)
criteria: 
gender: All
gender based: Yes
gender description: Balanced groups were produced based on the sex of the study subjects, that is, men and women were proportionally assigned in both groups.
minimum age: 20 Years
maximum age: 99 Years
healthy volunteers: No
last name: Rebeca García Román, PHD
role: Principal Investigator
affiliation: UV
facility: 
country: Mexico
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responsible party type: Principal Investigator
investigator affiliation: Universidad Veracruzana
investigator full name: María Cristina León
investigator title: Investigator
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
sharing ipd: No