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/NCT05965973</url>
    </required_header>
    <id_info>
      <org_study_id>INAF 2023-6814</org_study_id>
      <nct_id>NCT05965973</nct_id>
    </id_info>
    <brief_title>Diet Impact on Hepatic Transcriptomics and Lipidomics in Pre-diabetes</brief_title>
    <acronym>DGENE-NAFLD</acronym>
    <official_title>Short-term Impact of a Low Carbohydrate/High Unsaturated Fat Diet on Hepatic Transcriptomics and Lipidomics in Individuals With Pre-diabetes - A Pilot Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Laval University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Laval University</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>
        Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, affecting&#xD;
        25% to 30% of the global population and nearly one third of the population in North America.&#xD;
        NAFLD is defined as an excessive accumulation of lipids within hepatocytes in the absence of&#xD;
        significant alcohol consumption or other causes of chronic liver disease. These patients&#xD;
        usually present with hepatic steatosis observed on imaging studies and elevated liver enzymes&#xD;
        with clinical features of insulin resistance (IR), including pre-diabetes, type 2 diabetes&#xD;
        mellitus (T2DM), arterial hypertension, dyslipidemia, and visceral obesity. The minimum&#xD;
        criterion for a histologic diagnosis of NAFLD is &gt;5 percent steatotic hepatocytes in a liver&#xD;
        tissue section. The exact mechanism for the development of NAFLD is unclear, although the&#xD;
        current evidence indicates that it is likely a complex interplay among neurohormones,&#xD;
        intestinal dysbiosis, nutrition, and genetics. IR plays a crucial role in NAFLD&#xD;
        pathophysiology mainly by increasing adipocyte lipolysis, resulting in the circulation of&#xD;
        more free fatty acids available for hepatic uptake and increasing hepatic de novo&#xD;
        lipogenesis. There is yet no approved pharmacologic option for the treatment of NAFLD.&#xD;
        Current international guidelines on NAFLD emphasize the importance of lifestyle modifications&#xD;
        for all patients with NAFLD and recommend 7-10% of weight loss and a &quot;healthy diet&quot;, without&#xD;
        suggesting any particular diet. Recent data provide some support for the beneficial role of&#xD;
        low carbohydrate (CHO)/high unsaturated fatty acid (both monounsaturated (MUFAs) and&#xD;
        polyunsaturated (PUFAs)) dietary patterns for decreasing hepatic steatosis. This proposal&#xD;
        addresses this important research gap by leading to advances regarding the impact of a&#xD;
        short-term low CHO/high PUFAs/MUFAs dietary intervention on improving hepatic gene expression&#xD;
        profiles and lipid composition in individuals with pre-diabetes. The proposed study is unique&#xD;
        because all meals and foods will be provided to participants under carefully controlled&#xD;
        isocaloric conditions to maintain a constant bodyweight with optimal energy and macronutrient&#xD;
        intake control. The primary objective of the proposed research is to investigate how&#xD;
        replacement of dietary CHOs by unsaturated fatty acids (both PUFAs and MUFAs) affects liver&#xD;
        fat composition and liver transcriptomics in subjects with pre-diabetes.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">June 9, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2024</completion_date>
    <primary_completion_date type="Anticipated">March 31, 2024</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>Prevention</primary_purpose>
      <masking>Single (Participant)</masking>
      <masking_description>Triple (Participant, Investigator, Outcomes Assessor)</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Change in the expression of key genes in lipid metabolism including LDL-receptor, acetyl-CoA acetyltransferase 2, apolipoprotein B, proproprotein convertase subtilisin/kexin type 9, microsomal triglyceride transfer protein</measure>
      <time_frame>At Day 3 and day 20 (at the end of the two 3-day diets)</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in the expression of key genes in liver inflammation including C-reactive protein, Interleukin-6, Interleukin-15, cell adhesion molecules, E-selectin</measure>
      <time_frame>At Day 3 and day 20 (at the end of the two 3-day diets)</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in the expression of key genes in hepatic fibrogenesis including transforming growth factor beta 1, a-smooth muscle actin, type-1 collagen, connective tissue growth factor</measure>
      <time_frame>At Day 3 and day 20 (at the end of the two 3-day diets)</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in liver's key lipid pathways (lipidomics) including lysophosphatidylcholine, phosphatidylcholine, diglyceride.</measure>
      <time_frame>At Day 3 and day 20 (at the end of the two 3-day diets)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Identify bacteria strains involved in the control of blood glucose such as C elegans.</measure>
      <time_frame>At Day 3 and day 20 (at the end of the two 3-day diets)</time_frame>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">6</enrollment>
    <condition>Pre-diabetes</condition>
    <arm_group>
      <arm_group_label>Low fat diet</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>During 3 days, subjects eat a diet low in fat (percent of total caloric intake: 15.0% from proteins; 65.0% from carbohydrates; 20.0% from fat: 4.0% from saturated fat; 10.0% from monounsaturated fat; 6.0% from polyunsaturated fat</description>
    </arm_group>
    <arm_group>
      <arm_group_label>High fat diet</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>During 3 days, subjects eat a diet high in fat (percent of total caloric intake: 15.0% from proteins; 45.0% from carbohydrates; 40.0% from fat: 8.0% from saturated fat; 22.0% from monounsaturated fat; 10.0% from polyunsaturated fat</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Low fat diet</intervention_name>
      <description>During 3 days, subjects eat a diet low in fat (percent of total caloric intake: 15.0% from proteins; 65.0% from carbohydrates; 20.0% from fat: 4.0% from saturated fat; 10.0% from monounsaturated fat; 6.0% from polyunsaturated fat</description>
      <arm_group_label>High fat diet</arm_group_label>
      <arm_group_label>Low fat diet</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>High fat diet</intervention_name>
      <description>During 3 days, subjects eat a diet high in fat (percent of total caloric intake: 15.0% from proteins; 45.0% from carbohydrates; 40.0% from fat: 8.0% from saturated fat; 22.0% from monounsaturated fat; 10.0% from polyunsaturated fat</description>
      <arm_group_label>High fat diet</arm_group_label>
      <arm_group_label>Low fat diet</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Males and females 18 to 60 years of age.&#xD;
  &#xD;
            -  Non-smoker&#xD;
  &#xD;
            -  Waist circumference &gt; 102 cm for men and &gt; 88 cm for women.&#xD;
  &#xD;
            -  Plasma triglyceride levels &gt; 1,7 mmol/L at the screening visit.&#xD;
  &#xD;
            -  Fasting plasma glucose levels &gt; 6,1 mmol/L at the screening visit.&#xD;
  &#xD;
            -  Fasting plasma insulin levels above the upper limit of normal at the screening visit.&#xD;
  &#xD;
            -  Subjects must be willing to give written informed consent and able to adhere to the&#xD;
               diet schedule and visit schedule.&#xD;
  &#xD;
            -  Patients should be otherwise healthy, without abnormal renal function or coagulation.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients with extreme dyslipidemias, such as familial hypercholesterolemia will be&#xD;
               excluded.&#xD;
  &#xD;
            -  Subjects will be excluded if they have cardiovascular disease (CHD, cerebrovascular&#xD;
               disease or peripheral arterial disease) or if they are taking other medications known&#xD;
               to affect lipoprotein metabolism (eg. steroids, beta blockers, thiazide diuretics,&#xD;
               other lipid lowering agents, significant alcohol intake etc.).&#xD;
  &#xD;
            -  Subjects who are in a situation or have any condition that, in the opinion of the&#xD;
               investigator, may interfere with optimal participation in the study.&#xD;
  &#xD;
            -  Individuals with a history of mental instability, drug or alcohol abuse within the&#xD;
               past 2 years or individuals who have been treated or are being treated for severe&#xD;
               psychiatric illness that, in the opinion of the investigator, may interfere with&#xD;
               optimal participation in the study.&#xD;
  &#xD;
            -  Disorders of the hematologic, digestive, or central nervous systems, including&#xD;
               cerebrovascular disease and degenerative disease, that would limit study evaluation or&#xD;
               participation.&#xD;
  &#xD;
            -  Known impairment of renal function (creatinine &gt;2.0 mg/dL), dysproteinemia, nephrotic&#xD;
               syndrome, or other renal disease.&#xD;
  &#xD;
            -  Subjects with coagulopathy (prothrombin time [PT] or partial thromboplastin time [PTT]&#xD;
               at Visit 1 higher than 1.5 times control).&#xD;
  &#xD;
            -  Patients who are known to have tested positive for human immunodeficiency virus (HIV).&#xD;
  &#xD;
            -  Patients who have used any investigational drug within 30 days of the first clinic&#xD;
               visit.&#xD;
  &#xD;
            -  Diabetic patients are excluded from the study. Uncontrolled endocrine or metabolic&#xD;
               disease known to influence serum lipids or lipoproteins. Clinically euthyroid subjects&#xD;
               on replacement doses of thyroid hormone are eligible for enrollment.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>60 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Patrick Couture, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Laval University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Patrick Couture, MD, PhD</last_name>
      <phone>418-654-2106</phone>
      <email>patrick.couture@fmed.ulaval.ca</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>André Tremblay, PhD</last_name>
      <phone>418-656-2131</phone>
      <phone_ext>411417</phone_ext>
      <email>andre.tremblay@fsaa.ulaval.ca</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Institute of Nutrition and Functional Foods (INAF)</name>
        <address>
          <city>Québec</city>
          <state>Quebec</state>
          <zip>G1V 0A6</zip>
          <country>Canada</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Patrick Couture, MD, PhD</last_name>
        <phone>418-654-2106</phone>
        <email>patrick.couture@fmed.ulaval.ca</email>
      </contact>
      <contact_backup>
        <last_name>André Tremblay, PhD</last_name>
        <phone>418-656-2131</phone>
        <phone_ext>411417</phone_ext>
        <email>andre.tremblay@fsaa.ulaval.ca</email>
      </contact_backup>
      <investigator>
        <last_name>Patrick Couture, MD, PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Canada</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>June 12, 2023</study_first_submitted>
    <study_first_submitted_qc>July 20, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 28, 2023</study_first_posted>
    <last_update_submitted>July 20, 2023</last_update_submitted>
    <last_update_submitted_qc>July 20, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">July 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Laval University</investigator_affiliation>
      <investigator_full_name>Patrick Couture</investigator_full_name>
      <investigator_title>MD, PhD, FRCP (C)</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Diabetes Mellitus</mesh_term>
      <mesh_term>Prediabetic State</mesh_term>
      <mesh_term>Glucose Intolerance</mesh_term>
    </condition_browse>
    <!-- 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/NCT05965973
  org study id: INAF 2023-6814
  nct id: NCT05965973
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, affecting
        25% to 30% of the global population and nearly one third of the population in North America.
        NAFLD is defined as an excessive accumulation of lipids within hepatocytes in the absence of
        significant alcohol consumption or other causes of chronic liver disease. These patients
        usually present with hepatic steatosis observed on imaging studies and elevated liver enzymes
        with clinical features of insulin resistance (IR), including pre-diabetes, type 2 diabetes
        mellitus (T2DM), arterial hypertension, dyslipidemia, and visceral obesity. The minimum
        criterion for a histologic diagnosis of NAFLD is >5 percent steatotic hepatocytes in a liver
        tissue section. The exact mechanism for the development of NAFLD is unclear, although the
        current evidence indicates that it is likely a complex interplay among neurohormones,
        intestinal dysbiosis, nutrition, and genetics. IR plays a crucial role in NAFLD
        pathophysiology mainly by increasing adipocyte lipolysis, resulting in the circulation of
        more free fatty acids available for hepatic uptake and increasing hepatic de novo
        lipogenesis. There is yet no approved pharmacologic option for the treatment of NAFLD.
        Current international guidelines on NAFLD emphasize the importance of lifestyle modifications
        for all patients with NAFLD and recommend 7-10% of weight loss and a "healthy diet", without
        suggesting any particular diet. Recent data provide some support for the beneficial role of
        low carbohydrate (CHO)/high unsaturated fatty acid (both monounsaturated (MUFAs) and
        polyunsaturated (PUFAs)) dietary patterns for decreasing hepatic steatosis. This proposal
        addresses this important research gap by leading to advances regarding the impact of a
        short-term low CHO/high PUFAs/MUFAs dietary intervention on improving hepatic gene expression
        profiles and lipid composition in individuals with pre-diabetes. The proposed study is unique
        because all meals and foods will be provided to participants under carefully controlled
        isocaloric conditions to maintain a constant bodyweight with optimal energy and macronutrient
        intake control. The primary objective of the proposed research is to investigate how
        replacement of dietary CHOs by unsaturated fatty acids (both PUFAs and MUFAs) affects liver
        fat composition and liver transcriptomics in subjects with pre-diabetes.
  allocation: Randomized
  intervention model: Crossover Assignment
  primary purpose: Prevention
  masking: Single (Participant)
  masking description: Triple (Participant, Investigator, Outcomes Assessor)
  measure: Change in the expression of key genes in lipid metabolism including LDL-receptor, acetyl-CoA acetyltransferase 2, apolipoprotein B, proproprotein convertase subtilisin/kexin type 9, microsomal triglyceride transfer protein
  time frame: At Day 3 and day 20 (at the end of the two 3-day diets)
  measure: Change in the expression of key genes in liver inflammation including C-reactive protein, Interleukin-6, Interleukin-15, cell adhesion molecules, E-selectin
  time frame: At Day 3 and day 20 (at the end of the two 3-day diets)
  measure: Change in the expression of key genes in hepatic fibrogenesis including transforming growth factor beta 1, a-smooth muscle actin, type-1 collagen, connective tissue growth factor
  time frame: At Day 3 and day 20 (at the end of the two 3-day diets)
  measure: Change in liver's key lipid pathways (lipidomics) including lysophosphatidylcholine, phosphatidylcholine, diglyceride.
  time frame: At Day 3 and day 20 (at the end of the two 3-day diets)
  measure: Identify bacteria strains involved in the control of blood glucose such as C elegans.
  time frame: At Day 3 and day 20 (at the end of the two 3-day diets)
  arm group label: Low fat diet
  arm group type: Experimental
  description: During 3 days, subjects eat a diet low in fat (percent of total caloric intake: 15.0% from proteins; 65.0% from carbohydrates; 20.0% from fat: 4.0% from saturated fat; 10.0% from monounsaturated fat; 6.0% from polyunsaturated fat
  arm group label: High fat diet
  arm group type: Experimental
  description: During 3 days, subjects eat a diet high in fat (percent of total caloric intake: 15.0% from proteins; 45.0% from carbohydrates; 40.0% from fat: 8.0% from saturated fat; 22.0% from monounsaturated fat; 10.0% from polyunsaturated fat
  intervention type: Other
  intervention name: Low fat diet
  description: During 3 days, subjects eat a diet low in fat (percent of total caloric intake: 15.0% from proteins; 65.0% from carbohydrates; 20.0% from fat: 4.0% from saturated fat; 10.0% from monounsaturated fat; 6.0% from polyunsaturated fat
  arm group label: High fat diet
  arm group label: Low fat diet
  intervention type: Other
  intervention name: High fat diet
  description: During 3 days, subjects eat a diet high in fat (percent of total caloric intake: 15.0% from proteins; 45.0% from carbohydrates; 40.0% from fat: 8.0% from saturated fat; 22.0% from monounsaturated fat; 10.0% from polyunsaturated fat
  arm group label: High fat diet
  arm group label: Low fat diet
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 60 Years
  healthy volunteers: No
  last name: Patrick Couture, MD, PhD
  role: Principal Investigator
  affiliation: Laval University
  last name: Patrick Couture, MD, PhD
  phone: 418-654-2106
  email: patrick.couture@fmed.ulaval.ca
  last name: André Tremblay, PhD
  phone: 418-656-2131
  phone ext: 411417
  email: andre.tremblay@fsaa.ulaval.ca
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  country: Canada
  responsible party type: Principal Investigator
  investigator affiliation: Laval University
  investigator full name: Patrick Couture
  investigator title: MD, PhD, FRCP (C)
  mesh term: Diabetes Mellitus
  mesh term: Prediabetic State
  mesh term: Glucose Intolerance