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/NCT06035874</url>
    </required_header>
    <id_info>
      <org_study_id>B-LIFTMED001</org_study_id>
      <nct_id>NCT06035874</nct_id>
    </id_info>
    <brief_title>Effect of Bempedoic Acid on Liver Fat in Individuals With Nonalcoholic Fatty Liver Disease and Type 2 Diabetes</brief_title>
    <acronym>B-LIFT</acronym>
    <official_title>Effect of Bempedoic Acid on Liver Fat in Individuals With Nonalcoholic Fatty Liver Disease and Type 2 Diabetes: Randomized Controlled Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Medanta, The Medicity, India</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Diabetes &amp; Endocrinology Foundation</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Medanta, The Medicity, India</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>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions ranging from liver&#xD;
        steatosis (NAFL), steatohepatitis (NASH), advanced liver fibrosis and ultimately leads to&#xD;
        cirrhosis in a significant proportion of individuals. NAFLD is intimately associated with&#xD;
        insulin resistance and associated disorders, such as type 2 diabetes, metabolic syndrome and&#xD;
        dyslipidemia.&#xD;
  &#xD;
        Bempedoic acid, an ATP-citrate lyase inhibitor, is recently approved for patients with&#xD;
        dyslipidemia as a second line drug. Bempedoic acid reduces liver fat in mice model of NASH.&#xD;
        Data regarding the effect of bempedoic acid on human liver fat are scarce. Therefore, the&#xD;
        current study is planned to evaluate the effect of bempedoic acid or saroglitazar versus&#xD;
        standard treatment on liver and pancreatic fat content in patients with NAFLD&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        OBJECTIVE Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions ranging&#xD;
        from liver steatosis (NAFL), steatohepatitis (NASH), advanced liver fibrosis and ultimately&#xD;
        leads to cirrhosis in a significant proportion of individuals. NAFLD is intimately associated&#xD;
        with insulin resistance and associated disorders, such as type 2 diabetes, metabolic syndrome&#xD;
        and dyslipidemia.&#xD;
  &#xD;
        Bempedoic acid, an ATP-citrate lyase inhibitor, is recently approved for patients with&#xD;
        dyslipidemia as a second line drug. Bempedoic acid reduces liver fat in mice model of NASH.&#xD;
        Data regarding the effect of bempedoic acid on human liver fat are scarce. Therefore, the&#xD;
        current study is planned to evaluate the effect of bempedoic acid or saroglitazar versus&#xD;
        standard treatment on liver and pancreatic fat content in patients with NAFLD.&#xD;
  &#xD;
        Materials and methods&#xD;
  &#xD;
        Study design This B-LIFT (effect of Bempedoic acid on Liver fat content) trial is an&#xD;
        investigator initiated, open label, randomized clinical study to examine the effect of&#xD;
        bempedoic acid 180 mg tablet once a day for 24 weeks (Bemp group) versus standard treatment&#xD;
        (control group) on liver and pancreatic fat content. Hepatic steatosis (intracellular fat&#xD;
        accumulation in hepatocytes) will be measured by MRI-PDFF, a validated quantitative biomarker&#xD;
        for liver fat. Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM)&#xD;
        will be measured by Fibroscan. The study will be conducted according to the CONSORT&#xD;
        guidelines. The patient population for the trial will be derived from Medanta-The Medicity&#xD;
        Hospital endocrine out-patient clinic, who would primarily visit for management of type 2&#xD;
        diabetes and other co-morbidities. The study will be conducted in Medanta-The Medicity&#xD;
        Hospital, Gurugram, Haryana, which is a tertiary care center in North India. Patients deemed&#xD;
        eligible will be screened for the trial. The study will be registered at clinicaltrials.gov.&#xD;
        The clinical trial protocol will be presented for approval to the institutional ethics review&#xD;
        board. Informed written consent will be obtained from all the participants before enrolment&#xD;
        into the study.&#xD;
  &#xD;
        All patients will undergo a baseline assessment before randomization, including detailed&#xD;
        medical history, physical examination including anthropometry and biochemical evaluation.&#xD;
  &#xD;
        Randomization&#xD;
  &#xD;
        A research assistant will randomize the patients into Bem group or Control group in a 1:1&#xD;
        ratio using computer-generated numbers. It will be ensured that these are equal in number.&#xD;
        Opaque envelopes will be prepared with serial number on the top and the assigned group inside&#xD;
        the envelop. After recruiting the subjects, the envelop with corresponding serial number will&#xD;
        be opened and the subjects assign to the relevant groups after opening the envelop. The&#xD;
        patients will then be sent back to their respective consultants in the endocrine department&#xD;
        for initiation and/or adjustment of treatment for type 2 diabetes (according to randomization&#xD;
        into Bemp or control groups) and other co-morbidities.&#xD;
  &#xD;
        Study visits&#xD;
  &#xD;
        After careful assessment at the baseline visit, patients meeting all inclusion and exclusion&#xD;
        criteria will be randomized to receive bempedoic acid 180 mg once a day or the standard&#xD;
        treatment (no treatment for fatty liver, control group) for 24 weeks. Patients will be&#xD;
        advised to return to the out-patient endocrine clinic for follow-up visits at weeks 12 and&#xD;
        24.&#xD;
  &#xD;
        Primary outcome The primary outcome measure will be the difference of the change in liver fat&#xD;
        content from 0 (baseline) to 24 weeks between groups. [liver fat content as quantified by&#xD;
        MRI-PDFF in colocalized regions of interest (ROI) within each of the nine liver segments].&#xD;
  &#xD;
        Secondary outcomes&#xD;
  &#xD;
          1. The difference of the change in pancreatic fat content from 0 (baseline) to 24 weeks&#xD;
             between groups. [Pancreatic fat content as quantified by MRI PDFF].&#xD;
  &#xD;
          2. The difference of the change in controlled attenuation parameter (CAP) from 0 (baseline)&#xD;
             to 24 weeks between groups. [CAP will be assessed by transient elastography].&#xD;
  &#xD;
          3. The difference of the change in liver stiffness measurement (LSM) from 0 (baseline) to&#xD;
             24 weeks between groups. [LSM will be measured by transient elastography].&#xD;
  &#xD;
          4. Change between the groups in aspartate aminotransferase (AST) levels.&#xD;
  &#xD;
          5. Change between groups in alanine aminotransferase (ALT) levels.&#xD;
  &#xD;
          6. Change between groups in gamma-glutamyl transpeptidase (GGT) levels.&#xD;
  &#xD;
          7. Change between the groups in serum creatinine concentrations.&#xD;
  &#xD;
          8. Change between the groups in total cholesterol levels.&#xD;
  &#xD;
          9. Change between groups in triglycerides levels.&#xD;
  &#xD;
         10. Change between groups in LDL levels.&#xD;
  &#xD;
         11. Change between groups in HDL levels.&#xD;
  &#xD;
        MRI-PDFF protocols&#xD;
  &#xD;
        MRI-PDFF for fat quantification&#xD;
  &#xD;
        MRI-PDFF is a non-invasive, objective, and quantitative MR imaging-based biomarker that can&#xD;
        accurately estimate liver fat. MRI-PDFF has been demonstrated to be a robust technique for&#xD;
        assessing treatment response in NASH clinical trials. In this study, the time interval from&#xD;
        obtaining the baseline MRI-PDFF to initiating the study drug will be less than one week.&#xD;
  &#xD;
        MRI-PDFF for detailed fat mapping of the entire liver&#xD;
  &#xD;
        All MR examinations will be done by an experienced MR technologist in the Medanta Radiology&#xD;
        department under the direction of the radiologist investigator (SK). The radiologist&#xD;
        investigator, blinded to the patients' treatment group allocation, clinical and biochemical&#xD;
        data, and order of scans (baseline and follow-up), will perform the image analyses.&#xD;
  &#xD;
        ROI colocalization before and after treatment&#xD;
  &#xD;
        To assess longitudinal changes in liver fat content, one colocalized ROI will be placed in&#xD;
        each of the nine liver segments (nine separate ROIs) on the baseline and follow-up MRI&#xD;
        examinations.&#xD;
  &#xD;
        Statistical analysis Plan&#xD;
  &#xD;
        The analysis will include profiling of patients on different demographic, clinical and&#xD;
        laboratory parameters etc. Quantitative data will be presented in terms of means and standard&#xD;
        deviation and qualitative/categorical data will be presented as absolute numbers and&#xD;
        proportions. To compare between the two groups, the Chi-squared test or Fisher's exact test&#xD;
        will be used for categorical variables, and the independent samples t test or&#xD;
        Wilcoxon-Mann-Whitney U test will be used for the differences between continuous variables.&#xD;
        Pearson correlation coefficient will be used to evaluate correlations between variables.&#xD;
        Additional analyses of primary and secondary outcomes within treatment groups will be&#xD;
        performed by using two-tailed independent sample t tests, paired t tests, or non-parametric&#xD;
        tests, when indicated. P-value &lt; 0.05 is considered statistically significant. SPSS software&#xD;
        will be used for analysis.&#xD;
  &#xD;
        Sample size calculation&#xD;
  &#xD;
        Investigator assumed that a 5.0% difference in absolute liver fat content between bempedoic&#xD;
        acid versus control group would be the minimally appreciable and clinically relevant&#xD;
        difference. Based on the results of previous similar clinical studies involving ezetimibe and&#xD;
        empagliflozin, Investigator expected the bempedoic acid group to have a liver fat reduction&#xD;
        of &gt;5% compared to baseline, and control group to have &lt;2% reduction in liver fat compared to&#xD;
        baseline. With these assumptions the sample size per group works out as 30 in each group to&#xD;
        achieve a power of at least 90% with a β of 0.05. Therefore, Investigator plan to randomize&#xD;
        100 patients, 50 in each group to ensure adequate study power even with dropouts.&#xD;
  &#xD;
        Method of sample size calculation&#xD;
  &#xD;
        Assumptions:&#xD;
  &#xD;
        Change in absolute liver fat from baseline to week 24 in Bemp group (m1) = 5.0% Change in&#xD;
        absolute liver fat from baseline to week 24 in Saro group (m2) = 5.0% Change in absolute&#xD;
        liver fat from baseline to week 24 in Control group (m3) = 2.0% Confidence level -95% Power -&#xD;
        90% Coefficient of variation = 100%&#xD;
  &#xD;
        Formula for sample size calculation:&#xD;
  &#xD;
        n = (Zα+Zβ)2 * (σ12 + σ22)) / (m1-m2)2, where Zα is the value of normal distribution&#xD;
        corresponding to desired confidence level Zβ is the value of the Normal distribution&#xD;
        corresponding to desired power σ1 and σ2 are the standard deviation of the two groups With&#xD;
        these assumptions the sample size per group works out as 30. Investigator will randomize 50&#xD;
        in each group to ensure adequate power even after dropouts.&#xD;
  &#xD;
        Patient confidentiality&#xD;
  &#xD;
        Precautions will be taken to ensure confidentiality. Data collection forms will not reveal&#xD;
        the name of patients included in study. All the participants will be covered by insurance to&#xD;
        cover the cost of any untoward effect directly resulting from enrolment in the study.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 15, 2023</start_date>
    <completion_date type="Anticipated">December 1, 2024</completion_date>
    <primary_completion_date type="Anticipated">November 1, 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>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>The change in liver fat content</measure>
      <time_frame>Baseline to 24 Weeks</time_frame>
      <description>The primary outcome measure will be the difference of the change in liver fat content from 0 (baseline) to 24 weeks between groups</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>The change in pancreatic fat</measure>
      <time_frame>Baseline to 24 Weeks</time_frame>
      <description>The difference of the change in pancreatic fat content from 0 (baseline) to 24 weeks between groups. [Pancreatic fat content as quantified by MRI PDFF]</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The change in controlled attenuation parameter</measure>
      <time_frame>Baseline to 24 Weeks</time_frame>
      <description>The difference of the change in controlled attenuation parameter (CAP) from 0 (baseline) to 24 weeks between groups. [CAP will be assessed by transient elastography].</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The change in liver stiffness measurement (LSM)</measure>
      <time_frame>Baseline to 24 Weeks</time_frame>
      <description>The difference of the change in liver stiffness measurement (LSM) from 0 (baseline) to 24 weeks between groups. [LSM will be measured by transient elastography].</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change between the groups in aspartate aminotransferase (AST) levels</measure>
      <time_frame>Baseline to 24 Weeks</time_frame>
      <description>Change between the groups in aspartate aminotransferase (AST) levels</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change between groups in alanine aminotransferase (ALT) levels</measure>
      <time_frame>Baseline to 24 Weeks</time_frame>
      <description>Change between groups in alanine aminotransferase (ALT) levels</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change between groups in gamma-glutamyl transpeptidase (GGT) levels.</measure>
      <time_frame>Baseline to 24 Weeks</time_frame>
      <description>Change between groups in gamma-glutamyl transpeptidase (GGT) levels.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change between the groups in serum creatinine concentrations.</measure>
      <time_frame>Baseline to 24 Weeks</time_frame>
      <description>Change between the groups in serum creatinine concentrations.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change between the groups in total cholesterol levels.</measure>
      <time_frame>Baseline to 24 Weeks</time_frame>
      <description>Change between the groups in total cholesterol levels.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change between groups in triglycerides levels.</measure>
      <time_frame>Baseline to 24 Weeks</time_frame>
      <description>Change between groups in triglycerides levels.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change between groups in LDL levels</measure>
      <time_frame>Baseline to 24 Weeks</time_frame>
      <description>Change between groups in LDL levels</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change between groups in HDL levels</measure>
      <time_frame>Baseline to 24 Weeks</time_frame>
      <description>Change between groups in HDL levels</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">100</enrollment>
    <condition>Type 2 Diabetes</condition>
    <condition>Non Alcholic Fatty Liver Disease</condition>
    <arm_group>
      <arm_group_label>Bem group</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Patient will get Bempedoic acid along with the standard of Care</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control Group</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>Patient will get the standard of Care as per routine practice</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Bempedoic acid</intervention_name>
      <description>Patient willl be randomized 1:1 in both the arms</description>
      <arm_group_label>Bem group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. A man or woman, 20 years of age or above with the diagnosis of type 2 diabetes for at&#xD;
               least 3 months who meets all the following two criteria:&#xD;
  &#xD;
                 1. On standard anti-diabetic agents (metformin, DPP-4 inhibitors, sulphonylureas or&#xD;
                    insulin, in any combination) with an HbA1c of &gt;9% at screening&#xD;
  &#xD;
                 2. Have documented hepatic steatosis (MRI-PDFF &gt;5.6%) on screening MRI- PDFF&#xD;
  &#xD;
            2. Participants must be medically stable based on medical history, physical examination&#xD;
               and laboratory investigations.&#xD;
  &#xD;
            3. Participants must be willing and able to adhere to the prohibitions and restrictions&#xD;
               specified in this protocol.&#xD;
  &#xD;
            4. Each participant must sign an informed consent form (ICF) indicating that he or she&#xD;
               understands the purpose of the study and are willing to participate in the study.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. History of diabetic ketoacidosis, type 1 diabetes, pancreas or beta-cell&#xD;
               transplantation, or diabetes secondary to pancreatitis or pancreatectomy.&#xD;
  &#xD;
            2. History of brittle or labile glycemic control, with widely varying glucose&#xD;
               measurements by FPG or SMBG such that stable glucose control over the treatment period&#xD;
               would be unlikely.&#xD;
  &#xD;
            3. History of drug or alcohol abuse according to Diagnostic and Statistical Manual of&#xD;
               Mental Disorders (5th edition) (DSM-V) criteria within 3 years before Screening, or an&#xD;
               Alcohol Use Disorders Identification Test (AUDIT) with a score &gt;8, or alcohol&#xD;
               consumption of more than 20 g per day in the case of women and more than 30 g per day&#xD;
               in the case of men for at least three consecutive months during the previous 5 years.&#xD;
  &#xD;
            4. Thyroid stimulating hormone (TSH) value that is either &lt; 0.45 mIU/L or &gt;10 mIU/L at&#xD;
               Screening. Note: Subjects on thyroid hormone replacement therapy must be on a stable&#xD;
               dose and dosing regimen for at least 4 weeks prior to enrollment.&#xD;
  &#xD;
            5. Use of a PPAR-γ agonist [e.g., a thiazolidinedione (pioglitazone], an SGLT2 inhibitor&#xD;
               (e.g., canagliflozin, empagliflozin, dapagliflozin), GLP-1 receptor agonists (e.g.,&#xD;
               liraglutide, dulaglutide) or saroglitazar (Dual PPARα/γ agonist) within 12 weeks&#xD;
               before the enrollment.&#xD;
  &#xD;
            6. BMI &gt;40 kg/m2.&#xD;
  &#xD;
            7. Ongoing eating disorder, or a significant weight loss or weight gain within 12 weeks&#xD;
               before the Screening visit, defined as an increase or decrease of 5% in body weight&#xD;
               based upon clinic-based measurement or, if not available, based on subject's report.&#xD;
  &#xD;
            8. Use of weight loss medication (prescription and/or over the counter) within 3 months&#xD;
               prior to Screening or have participated in a weight loss/diet program within 12 months&#xD;
               prior to Screening.&#xD;
  &#xD;
            9. Renal disease that required treatment with immunosuppressive therapy or a history of&#xD;
               dialysis or renal transplant.&#xD;
  &#xD;
           10. Myocardial infarction, unstable angina, pulmonary hypertension, revascularization&#xD;
               procedure (e.g., stent or bypass graft surgery), or cerebrovascular accident within 3&#xD;
               months before Screening, or revascularization procedure is planned, or subject has a&#xD;
               history of New York Heart Association (NYHA) Class III-IV cardiac disease.&#xD;
  &#xD;
           11. History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV)&#xD;
               positive, or other clinically active liver disease, or tests positive for HBsAg or&#xD;
               anti- HCV at Screening.&#xD;
  &#xD;
           12. Use of vitamin E within 12 weeks before screening.&#xD;
  &#xD;
           13. History of prior bariatric (e.g., Roux-en-Y gastric bypass) or other major upper&#xD;
               gastrointestinal surgical procedure (including gastric resection).&#xD;
  &#xD;
           14. History of diabetic gastroparesis (or symptoms suggestive of this disorder, including&#xD;
               postprandial bloating or vomiting), malabsorption, inflammatory bowel disease, or any&#xD;
               other chronic, clinically important gastrointestinal disorder.&#xD;
  &#xD;
           15. Estimated glomerular filtration rate (eGFR) &lt;60 mL/min/1•73 m2 using the Modification&#xD;
               of Diet in Renal Disease Study (MDRD) equation.&#xD;
  &#xD;
           16. Subjects with a history of having or possibly having metallic material in the body or&#xD;
               any contraindication for a MR examination.&#xD;
  &#xD;
           17. Claustrophobia, or anxiety related to previous negative experiences with magnetic&#xD;
               resonance imaging procedures or if the subject is unwilling to participate in magnetic&#xD;
               resonance imaging procedures.&#xD;
  &#xD;
           18. Clinically important hematologic disorder (e.g., symptomatic anemia, proliferative&#xD;
               bone marrow disorder, thrombocytopenia) at Screening.&#xD;
  &#xD;
           19. History of human immunodeficiency virus (HIV) antibody positive at Screening.&#xD;
  &#xD;
           20. Major surgery (e.g., requiring general anesthesia) within 12 weeks before Screening,&#xD;
               or will not have fully recovered from surgery, or has surgery planned during the time&#xD;
               the subject is expected to participate in the study.&#xD;
  &#xD;
           21. Contraindications to the use of bempedoic acid (per BEMPEDOIC ACID Prescribing&#xD;
               Information).&#xD;
  &#xD;
           22. Current use of a corticosteroid medication or immunosuppressive agent, or likely to&#xD;
               require treatment with a corticosteroid medication or an immunosuppressive agent.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>20 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Mr Surender, PhD</last_name>
      <phone>01244141414</phone>
      <phone_ext>6596</phone_ext>
      <email>yadavsurender89@gmail.com</email>
    </overall_contact>
    <results_reference>
      <citation>Malik SM, Devera ME, Fontes P, Shaikh O, Sasatomi E, Ahmad J. Recurrent disease following liver transplantation for nonalcoholic steatohepatitis cirrhosis. Liver Transpl. 2009 Dec;15(12):1843-51. doi: 10.1002/lt.21943.</citation>
      <PMID>19938117</PMID>
    </results_reference>
    <results_reference>
      <citation>Reeder SB, Cruite I, Hamilton G, Sirlin CB. Quantitative Assessment of Liver Fat with Magnetic Resonance Imaging and Spectroscopy. J Magn Reson Imaging. 2011 Oct;34(4):729-749. doi: 10.1002/jmri.22775. Epub 2011 Sep 16.</citation>
      <PMID>22025886</PMID>
    </results_reference>
    <results_reference>
      <citation>Permutt Z, Le TA, Peterson MR, Seki E, Brenner DA, Sirlin C, Loomba R. Correlation between liver histology and novel magnetic resonance imaging in adult patients with non-alcoholic fatty liver disease - MRI accurately quantifies hepatic steatosis in NAFLD. Aliment Pharmacol Ther. 2012 Jul;36(1):22-9. doi: 10.1111/j.1365-2036.2012.05121.x. Epub 2012 May 3.</citation>
      <PMID>22554256</PMID>
    </results_reference>
    <results_reference>
      <citation>Le TA, Chen J, Changchien C, Peterson MR, Kono Y, Patton H, Cohen BL, Brenner D, Sirlin C, Loomba R; San Diego Integrated NAFLD Research Consortium (SINC). Effect of colesevelam on liver fat quantified by magnetic resonance in nonalcoholic steatohepatitis: a randomized controlled trial. Hepatology. 2012 Sep;56(3):922-32. doi: 10.1002/hep.25731. Epub 2012 Jul 2.</citation>
      <PMID>22431131</PMID>
    </results_reference>
    <results_reference>
      <citation>Loomba R, Sirlin CB, Ang B, Bettencourt R, Jain R, Salotti J, Soaft L, Hooker J, Kono Y, Bhatt A, Hernandez L, Nguyen P, Noureddin M, Haufe W, Hooker C, Yin M, Ehman R, Lin GY, Valasek MA, Brenner DA, Richards L; San Diego Integrated NAFLD Research Consortium (SINC). Ezetimibe for the treatment of nonalcoholic steatohepatitis: assessment by novel magnetic resonance imaging and magnetic resonance elastography in a randomized trial (MOZART trial). Hepatology. 2015 Apr;61(4):1239-50. doi: 10.1002/hep.27647. Epub 2015 Feb 27.</citation>
      <PMID>25482832</PMID>
    </results_reference>
    <results_reference>
      <citation>Sanjay KV, Vishwakarma S, Zope BR, Mane VS, Mohire S, Dhakshinamoorthy S. ATP citrate lyase inhibitor Bempedoic Acid alleviate long term HFD induced NASH through improvement in glycemic control, reduction of hepatic triglycerides &amp; total cholesterol, modulation of inflammatory &amp; fibrotic genes and improvement in NAS score. Curr Res Pharmacol Drug Discov. 2021 Sep 4;2:100051. doi: 10.1016/j.crphar.2021.100051. eCollection 2021.</citation>
      <PMID>34909677</PMID>
    </results_reference>
    <results_reference>
      <citation>Bentanachs R, Velazquez AM, Sanchez RM, Alegret M, Laguna JC, Roglans N. Bempedoic acid as a PPARalpha activator: new perspectives for hepatic steatosis treatment in a female rat experimental model. Clin Investig Arterioscler. 2022 Mar-Apr;34(2):57-67. doi: 10.1016/j.arteri.2021.09.004. Epub 2021 Dec 6. English, Spanish.</citation>
      <PMID>34887111</PMID>
    </results_reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 6, 2023</study_first_submitted>
    <study_first_submitted_qc>September 6, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 14, 2023</last_update_submitted>
    <last_update_submitted_qc>September 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Medanta, The Medicity, India</investigator_affiliation>
      <investigator_full_name>Dr Mohammad Shafi Kuchay</investigator_full_name>
      <investigator_title>Senior Consultant, Division of Endocrinology &amp; Diabetes</investigator_title>
    </responsible_party>
    <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>
      <mesh_term>Diabetes Mellitus</mesh_term>
      <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Undecided</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/NCT06035874
  org study id: B-LIFTMED001
  nct id: NCT06035874
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions ranging from liver
        steatosis (NAFL), steatohepatitis (NASH), advanced liver fibrosis and ultimately leads to
        cirrhosis in a significant proportion of individuals. NAFLD is intimately associated with
        insulin resistance and associated disorders, such as type 2 diabetes, metabolic syndrome and
        dyslipidemia.
  
        Bempedoic acid, an ATP-citrate lyase inhibitor, is recently approved for patients with
        dyslipidemia as a second line drug. Bempedoic acid reduces liver fat in mice model of NASH.
        Data regarding the effect of bempedoic acid on human liver fat are scarce. Therefore, the
        current study is planned to evaluate the effect of bempedoic acid or saroglitazar versus
        standard treatment on liver and pancreatic fat content in patients with NAFLD
  OBJECTIVE Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions ranging
        from liver steatosis (NAFL), steatohepatitis (NASH), advanced liver fibrosis and ultimately
        leads to cirrhosis in a significant proportion of individuals. NAFLD is intimately associated
        with insulin resistance and associated disorders, such as type 2 diabetes, metabolic syndrome
        and dyslipidemia.
  
        Bempedoic acid, an ATP-citrate lyase inhibitor, is recently approved for patients with
        dyslipidemia as a second line drug. Bempedoic acid reduces liver fat in mice model of NASH.
        Data regarding the effect of bempedoic acid on human liver fat are scarce. Therefore, the
        current study is planned to evaluate the effect of bempedoic acid or saroglitazar versus
        standard treatment on liver and pancreatic fat content in patients with NAFLD.
  
        Materials and methods
  
        Study design This B-LIFT (effect of Bempedoic acid on Liver fat content) trial is an
        investigator initiated, open label, randomized clinical study to examine the effect of
        bempedoic acid 180 mg tablet once a day for 24 weeks (Bemp group) versus standard treatment
        (control group) on liver and pancreatic fat content. Hepatic steatosis (intracellular fat
        accumulation in hepatocytes) will be measured by MRI-PDFF, a validated quantitative biomarker
        for liver fat. Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM)
        will be measured by Fibroscan. The study will be conducted according to the CONSORT
        guidelines. The patient population for the trial will be derived from Medanta-The Medicity
        Hospital endocrine out-patient clinic, who would primarily visit for management of type 2
        diabetes and other co-morbidities. The study will be conducted in Medanta-The Medicity
        Hospital, Gurugram, Haryana, which is a tertiary care center in North India. Patients deemed
        eligible will be screened for the trial. The study will be registered at clinicaltrials.gov.
        The clinical trial protocol will be presented for approval to the institutional ethics review
        board. Informed written consent will be obtained from all the participants before enrolment
        into the study.
  
        All patients will undergo a baseline assessment before randomization, including detailed
        medical history, physical examination including anthropometry and biochemical evaluation.
  
        Randomization
  
        A research assistant will randomize the patients into Bem group or Control group in a 1:1
        ratio using computer-generated numbers. It will be ensured that these are equal in number.
        Opaque envelopes will be prepared with serial number on the top and the assigned group inside
        the envelop. After recruiting the subjects, the envelop with corresponding serial number will
        be opened and the subjects assign to the relevant groups after opening the envelop. The
        patients will then be sent back to their respective consultants in the endocrine department
        for initiation and/or adjustment of treatment for type 2 diabetes (according to randomization
        into Bemp or control groups) and other co-morbidities.
  
        Study visits
  
        After careful assessment at the baseline visit, patients meeting all inclusion and exclusion
        criteria will be randomized to receive bempedoic acid 180 mg once a day or the standard
        treatment (no treatment for fatty liver, control group) for 24 weeks. Patients will be
        advised to return to the out-patient endocrine clinic for follow-up visits at weeks 12 and
        24.
  
        Primary outcome The primary outcome measure will be the difference of the change in liver fat
        content from 0 (baseline) to 24 weeks between groups. [liver fat content as quantified by
        MRI-PDFF in colocalized regions of interest (ROI) within each of the nine liver segments].
  
        Secondary outcomes
  
          1. The difference of the change in pancreatic fat content from 0 (baseline) to 24 weeks
             between groups. [Pancreatic fat content as quantified by MRI PDFF].
  
          2. The difference of the change in controlled attenuation parameter (CAP) from 0 (baseline)
             to 24 weeks between groups. [CAP will be assessed by transient elastography].
  
          3. The difference of the change in liver stiffness measurement (LSM) from 0 (baseline) to
             24 weeks between groups. [LSM will be measured by transient elastography].
  
          4. Change between the groups in aspartate aminotransferase (AST) levels.
  
          5. Change between groups in alanine aminotransferase (ALT) levels.
  
          6. Change between groups in gamma-glutamyl transpeptidase (GGT) levels.
  
          7. Change between the groups in serum creatinine concentrations.
  
          8. Change between the groups in total cholesterol levels.
  
          9. Change between groups in triglycerides levels.
  
         10. Change between groups in LDL levels.
  
         11. Change between groups in HDL levels.
  
        MRI-PDFF protocols
  
        MRI-PDFF for fat quantification
  
        MRI-PDFF is a non-invasive, objective, and quantitative MR imaging-based biomarker that can
        accurately estimate liver fat. MRI-PDFF has been demonstrated to be a robust technique for
        assessing treatment response in NASH clinical trials. In this study, the time interval from
        obtaining the baseline MRI-PDFF to initiating the study drug will be less than one week.
  
        MRI-PDFF for detailed fat mapping of the entire liver
  
        All MR examinations will be done by an experienced MR technologist in the Medanta Radiology
        department under the direction of the radiologist investigator (SK). The radiologist
        investigator, blinded to the patients' treatment group allocation, clinical and biochemical
        data, and order of scans (baseline and follow-up), will perform the image analyses.
  
        ROI colocalization before and after treatment
  
        To assess longitudinal changes in liver fat content, one colocalized ROI will be placed in
        each of the nine liver segments (nine separate ROIs) on the baseline and follow-up MRI
        examinations.
  
        Statistical analysis Plan
  
        The analysis will include profiling of patients on different demographic, clinical and
        laboratory parameters etc. Quantitative data will be presented in terms of means and standard
        deviation and qualitative/categorical data will be presented as absolute numbers and
        proportions. To compare between the two groups, the Chi-squared test or Fisher's exact test
        will be used for categorical variables, and the independent samples t test or
        Wilcoxon-Mann-Whitney U test will be used for the differences between continuous variables.
        Pearson correlation coefficient will be used to evaluate correlations between variables.
        Additional analyses of primary and secondary outcomes within treatment groups will be
        performed by using two-tailed independent sample t tests, paired t tests, or non-parametric
        tests, when indicated. P-value < 0.05 is considered statistically significant. SPSS software
        will be used for analysis.
  
        Sample size calculation
  
        Investigator assumed that a 5.0% difference in absolute liver fat content between bempedoic
        acid versus control group would be the minimally appreciable and clinically relevant
        difference. Based on the results of previous similar clinical studies involving ezetimibe and
        empagliflozin, Investigator expected the bempedoic acid group to have a liver fat reduction
        of >5% compared to baseline, and control group to have <2% reduction in liver fat compared to
        baseline. With these assumptions the sample size per group works out as 30 in each group to
        achieve a power of at least 90% with a β of 0.05. Therefore, Investigator plan to randomize
        100 patients, 50 in each group to ensure adequate study power even with dropouts.
  
        Method of sample size calculation
  
        Assumptions:
  
        Change in absolute liver fat from baseline to week 24 in Bemp group (m1) = 5.0% Change in
        absolute liver fat from baseline to week 24 in Saro group (m2) = 5.0% Change in absolute
        liver fat from baseline to week 24 in Control group (m3) = 2.0% Confidence level -95% Power -
        90% Coefficient of variation = 100%
  
        Formula for sample size calculation:
  
        n = (Zα+Zβ)2 * (σ12 + σ22)) / (m1-m2)2, where Zα is the value of normal distribution
        corresponding to desired confidence level Zβ is the value of the Normal distribution
        corresponding to desired power σ1 and σ2 are the standard deviation of the two groups With
        these assumptions the sample size per group works out as 30. Investigator will randomize 50
        in each group to ensure adequate power even after dropouts.
  
        Patient confidentiality
  
        Precautions will be taken to ensure confidentiality. Data collection forms will not reveal
        the name of patients included in study. All the participants will be covered by insurance to
        cover the cost of any untoward effect directly resulting from enrolment in the study.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: The change in liver fat content
  time frame: Baseline to 24 Weeks
  description: The primary outcome measure will be the difference of the change in liver fat content from 0 (baseline) to 24 weeks between groups
  measure: The change in pancreatic fat
  time frame: Baseline to 24 Weeks
  description: The difference of the change in pancreatic fat content from 0 (baseline) to 24 weeks between groups. [Pancreatic fat content as quantified by MRI PDFF]
  measure: The change in controlled attenuation parameter
  time frame: Baseline to 24 Weeks
  description: The difference of the change in controlled attenuation parameter (CAP) from 0 (baseline) to 24 weeks between groups. [CAP will be assessed by transient elastography].
  measure: The change in liver stiffness measurement (LSM)
  time frame: Baseline to 24 Weeks
  description: The difference of the change in liver stiffness measurement (LSM) from 0 (baseline) to 24 weeks between groups. [LSM will be measured by transient elastography].
  measure: Change between the groups in aspartate aminotransferase (AST) levels
  time frame: Baseline to 24 Weeks
  description: Change between the groups in aspartate aminotransferase (AST) levels
  measure: Change between groups in alanine aminotransferase (ALT) levels
  time frame: Baseline to 24 Weeks
  description: Change between groups in alanine aminotransferase (ALT) levels
  measure: Change between groups in gamma-glutamyl transpeptidase (GGT) levels.
  time frame: Baseline to 24 Weeks
  description: Change between groups in gamma-glutamyl transpeptidase (GGT) levels.
  measure: Change between the groups in serum creatinine concentrations.
  time frame: Baseline to 24 Weeks
  description: Change between the groups in serum creatinine concentrations.
  measure: Change between the groups in total cholesterol levels.
  time frame: Baseline to 24 Weeks
  description: Change between the groups in total cholesterol levels.
  measure: Change between groups in triglycerides levels.
  time frame: Baseline to 24 Weeks
  description: Change between groups in triglycerides levels.
  measure: Change between groups in LDL levels
  time frame: Baseline to 24 Weeks
  description: Change between groups in LDL levels
  measure: Change between groups in HDL levels
  time frame: Baseline to 24 Weeks
  description: Change between groups in HDL levels
  arm group label: Bem group
  arm group type: Active Comparator
  description: Patient will get Bempedoic acid along with the standard of Care
  arm group label: Control Group
  arm group type: No Intervention
  description: Patient will get the standard of Care as per routine practice
  intervention type: Drug
  intervention name: Bempedoic acid
  description: Patient willl be randomized 1:1 in both the arms
  arm group label: Bem group
  criteria: 
  gender: All
  minimum age: 20 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Mr Surender, PhD
  phone: 01244141414
  phone ext: 6596
  email: yadavsurender89@gmail.com
  citation: Malik SM, Devera ME, Fontes P, Shaikh O, Sasatomi E, Ahmad J. Recurrent disease following liver transplantation for nonalcoholic steatohepatitis cirrhosis. Liver Transpl. 2009 Dec;15(12):1843-51. doi: 10.1002/lt.21943.
  PMID: 19938117
  citation: Reeder SB, Cruite I, Hamilton G, Sirlin CB. Quantitative Assessment of Liver Fat with Magnetic Resonance Imaging and Spectroscopy. J Magn Reson Imaging. 2011 Oct;34(4):729-749. doi: 10.1002/jmri.22775. Epub 2011 Sep 16.
  PMID: 22025886
  citation: Permutt Z, Le TA, Peterson MR, Seki E, Brenner DA, Sirlin C, Loomba R. Correlation between liver histology and novel magnetic resonance imaging in adult patients with non-alcoholic fatty liver disease - MRI accurately quantifies hepatic steatosis in NAFLD. Aliment Pharmacol Ther. 2012 Jul;36(1):22-9. doi: 10.1111/j.1365-2036.2012.05121.x. Epub 2012 May 3.
  PMID: 22554256
  citation: Le TA, Chen J, Changchien C, Peterson MR, Kono Y, Patton H, Cohen BL, Brenner D, Sirlin C, Loomba R; San Diego Integrated NAFLD Research Consortium (SINC). Effect of colesevelam on liver fat quantified by magnetic resonance in nonalcoholic steatohepatitis: a randomized controlled trial. Hepatology. 2012 Sep;56(3):922-32. doi: 10.1002/hep.25731. Epub 2012 Jul 2.
  PMID: 22431131
  citation: Loomba R, Sirlin CB, Ang B, Bettencourt R, Jain R, Salotti J, Soaft L, Hooker J, Kono Y, Bhatt A, Hernandez L, Nguyen P, Noureddin M, Haufe W, Hooker C, Yin M, Ehman R, Lin GY, Valasek MA, Brenner DA, Richards L; San Diego Integrated NAFLD Research Consortium (SINC). Ezetimibe for the treatment of nonalcoholic steatohepatitis: assessment by novel magnetic resonance imaging and magnetic resonance elastography in a randomized trial (MOZART trial). Hepatology. 2015 Apr;61(4):1239-50. doi: 10.1002/hep.27647. Epub 2015 Feb 27.
  PMID: 25482832
  citation: Sanjay KV, Vishwakarma S, Zope BR, Mane VS, Mohire S, Dhakshinamoorthy S. ATP citrate lyase inhibitor Bempedoic Acid alleviate long term HFD induced NASH through improvement in glycemic control, reduction of hepatic triglycerides & total cholesterol, modulation of inflammatory & fibrotic genes and improvement in NAS score. Curr Res Pharmacol Drug Discov. 2021 Sep 4;2:100051. doi: 10.1016/j.crphar.2021.100051. eCollection 2021.
  PMID: 34909677
  citation: Bentanachs R, Velazquez AM, Sanchez RM, Alegret M, Laguna JC, Roglans N. Bempedoic acid as a PPARalpha activator: new perspectives for hepatic steatosis treatment in a female rat experimental model. Clin Investig Arterioscler. 2022 Mar-Apr;34(2):57-67. doi: 10.1016/j.arteri.2021.09.004. Epub 2021 Dec 6. English, Spanish.
  PMID: 34887111
  responsible party type: Principal Investigator
  investigator affiliation: Medanta, The Medicity, India
  investigator full name: Dr Mohammad Shafi Kuchay
  investigator title: Senior Consultant, Division of Endocrinology & Diabetes
  mesh term: Liver Diseases
  mesh term: Fatty Liver
  mesh term: Non-alcoholic Fatty Liver Disease
  mesh term: Diabetes Mellitus
  mesh term: Diabetes Mellitus, Type 2
  mesh term: 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
  sharing ipd: Undecided