<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/NCT03836937</url>
  </required_header>
  <id_info>
    <org_study_id>SirSalimullahMCMH</org_study_id>
    <nct_id>NCT03836937</nct_id>
  </id_info>
  <brief_title>Role of Obeticholic Acid in the Patients of NAFLD With Raised ALT</brief_title>
  <acronym>NAFLD</acronym>
  <official_title>Role of Obeticholic Acid in the Patients of NAFLD With Raised ALT- A Randomized Clinical Control Trial Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sir Salimullah Medical College Mitford Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sir Salimullah Medical College Mitford Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will be conducted upon the patients with fatty liver disease. Patients who will be&#xD;
      diagnosed as a case of fatty liver disease by ultrasound with raised liver enzyme (ALT) will&#xD;
      be primarily selected for the study. A total number of 70 patients will be randomly selected&#xD;
      for the study that will also be divided into two groups for the study purpose. The patients&#xD;
      will be informed about the details of the study. After getting the detail information those&#xD;
      who will give informed written consent will be finally included in the study. One group of&#xD;
      patients will be treated by both life style modification and Obeticholic acid. Another group&#xD;
      of patients by only life style modification. After 3 months of treatment the two groups will&#xD;
      be compared of improvement of fatty liver disease and liver enzyme by improvement of&#xD;
      fibroscan with CAP value as well as improvement of ALT value.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Non-alcoholic fatty liver disease (NAFLD) is an increasingly common cause of chronic liver&#xD;
      disease worldwide and it is associated with increased liver-related mortality and&#xD;
      hepatocellular carcinoma, even in the absence of cirrhosis. The prevalence of NAFLD is&#xD;
      steadily increasing and is currently 20%-30% in Western countries and 5%-18% in Asia. It&#xD;
      progresses to cirrhosis in 15-20% of affected individuals and is a rising indication for&#xD;
      liver transplantation. NAFLD is the commonest cause of elevated liver enzymes. Lifestyle&#xD;
      modifications, including diet and exercise, are imperative for achieving weight loss and&#xD;
      reducing insulin resistance and hepatic steatosis and inflammation in patients with NAFLD.&#xD;
      But are suboptimal by long-term adherence in patients with NAFLD. On the other hand, current&#xD;
      pharmacological treatment of NAFLD has limited efficacy and unfavorable safety profile. In&#xD;
      this context, obeticholic acid, a selective agonist of the farnesoid X receptors, might&#xD;
      represent a useful option in these patients. Preclinical studies suggest that obeticholic&#xD;
      acid improves hepatic steatosis, inflammation and fibrosis. A randomized, placebo-controlled&#xD;
      Farnesoid X Receptor Ligand Obeticholic Acid in non-alcoholic steatohepatitis Treatment&#xD;
      (FLINT) trial also showed improvements in liver histology in patients with NAFLD who received&#xD;
      obeticholic acid. So, there is a need to develop more effective and safe agents for this&#xD;
      common and life-threatening disease.&#xD;
&#xD;
      Farnesoid X receptor (FXR) is a member of the nuclear receptor super family expressed in the&#xD;
      liver, kidney, intestine and adrenal glands. In addition to regulation of bile acid (BA)&#xD;
      synthesis, several lines of evidence have suggested that FXR plays a role in the&#xD;
      pathophysiology of NAFLD/NASH. Obeticholic acid is a synthetically modified bile acid that is&#xD;
      a potent agonist of the farnesoid X nuclear receptor (FXR), a nuclear receptor with major&#xD;
      effects on bile acid synthesis and transport as well as lipid metabolism and glucose&#xD;
      homeostasis. Obeticholic acid has been shown to improve serum enzymes in several diseases&#xD;
      including nonalcoholic fatty liver disease and primary biliary cirrhosis. In FLINT trial&#xD;
      treatment with obeticholic acid (25 mg/day for 72 weeks) resulted in a highly statistically&#xD;
      significant improvement in the NAFLD Activity Score of at least two points, with no worsening&#xD;
      of fibrosis. 45% (50 of 110) of the treated group had this improvement compared with 21% (23&#xD;
      of 109) of the placebo-treated controls.&#xD;
&#xD;
      The objective of the study will be to assess the efficacy of obeticholic acid on improvement&#xD;
      of NAFLD and ALT values in patients with fatty liver disease.&#xD;
&#xD;
      The study will be conducted in the department of Hepatology, Sir Salimullah Medical College&#xD;
      and Mitford Hospital. It will be a randomized open label clinical control trial study.&#xD;
      Patients diagnosed with non-alcoholic fatty liver disease (NAFLD) will be initially targeted&#xD;
      for the study. Patients who will be diagnosed as a case of NAFLD by ultrasound with raised&#xD;
      Alanin aminotransferase (ALT) (&gt;40 U/L) will be primarily selected for the study. The total&#xD;
      sample size will be 70 that will be divided into two groups (Group-A and Group-B) for the&#xD;
      study purpose. The patients will be informed about the details of the study. After getting&#xD;
      the detail information, those who will give informed written consent will be finally included&#xD;
      in the study. A series of baseline investigations including CBC with ESR, fasting blood sugar&#xD;
      (FBS), 2 hours after 75 g glucose, alanine aminotransferase (ALT), aspartate-aminotransferase&#xD;
      (AST), gamma-glutamyl transpeptidase (GGT), bilirubin (B), PT with INR, serum albumin, total&#xD;
      cholesterol (TC) &amp; triglycerides (TG), LDL-C, HDL-C, Thyroid function test will be determined&#xD;
      on fresh serum using an auto-analyzer. Fibroscan with CAP as well as ALT will be done to&#xD;
      assess the baseline status of the patients at the time of enrollment of the study. Group-A&#xD;
      patients will be treated by both life style modification and Obeticholic acid and Group-B&#xD;
      patients by only life style modification. We shall give 10 mg obeticholic acid twice daily to&#xD;
      the patients of Group-1. Life style modification including moderate exercise that is 30&#xD;
      minutes brisk walking a day with dietary advice to avoid fatty foods and excessive sugar&#xD;
      containing diet and intake of at least 3 vegetables per day will be advised to all the&#xD;
      patients in both Groups. The patients will be followed for 3 months. Patients will come for&#xD;
      follow-up after 1 month and finally after 3 months. Each visit will take place between 10.00&#xD;
      am to 02.00 p.m. &amp; consist with a clinical examination, blood pressure (BP) &amp; body mass index&#xD;
      (BMI) determinations and a questionnaire. BMI will be computed using the formula: [weight&#xD;
      (kg)]/ [square of height (meters)]. Serum will be collected for CBC with ESR, FBS, 2 hours&#xD;
      after 75 g glucose, ALT, AST, PT with INR, serum albumin, GGT, TC, TG, HDL, LDL in first and&#xD;
      last visit. An alcohol consumption questionnaire will also be administered in each visit and&#xD;
      study compliance will be strictly monitored. After 3 months of treatment the two groups will&#xD;
      be compared of improvement of NAFLD and liver enzyme by improvement of fibroscan with CAP&#xD;
      value as well as improvement of ALT value with the baseline ALT and fibroscan with CAP&#xD;
      values.&#xD;
&#xD;
      All Data will be presented as mean ± SD &amp; analyzed by SPSS (version 23). Qualitative data&#xD;
      will be analyzed by Chi-square test &amp; quantitative data will be analyzed by student's t-test.&#xD;
      A statistically significant result will be considered when P value &lt; 0.05.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 5, 2019</start_date>
  <completion_date type="Actual">December 31, 2021</completion_date>
  <primary_completion_date type="Actual">November 30, 2020</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>Open label randomized clinical control trial study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in fibroscan score (Kpa) and CAP value (Kpa) which signifies fibrosis and steatosis status respectively.</measure>
    <time_frame>For 12 weeks from the date of enrollment of the patient.</time_frame>
    <description>Obeticholic acid and life style modification improve fibroscan with CAP results in patients with NAFLD.&#xD;
Change in symptoms after 12 weeks of treatment or life style modification.&#xD;
Change in liver function test, fibroscan values and CAP values after treatment or life style modification.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in BMI (weight in kg/height in meter square)</measure>
    <time_frame>For 12 weeks from the date of enrollment of the patient.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in ALT (U/L)</measure>
    <time_frame>For 12 weeks from the date of enrollment of the patient.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Fasting blood sugar (FBS) (mmol/L)</measure>
    <time_frame>For 12 weeks from the date of enrollment of the patient.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>2 hours after 75 gm glucose (mmol/L)</measure>
    <time_frame>For 12 weeks from the date of enrollment of the patient</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Serum bilirubin (mg/dl)</measure>
    <time_frame>For 12 weeks from the date of enrollment of the patient</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Aspertate aminotransferase (AST) (U/L)</measure>
    <time_frame>For 12 weeks from the date of enrollment of the patient</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Gamma glutamyle transpeptidase (GGT) (U/L)</measure>
    <time_frame>For 12 weeks from the date of enrollment of the patient</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Serum albumin (gm/dl)</measure>
    <time_frame>For 12 weeks from the date of enrollment of the patient</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Prothrombin time (PT) (sec)</measure>
    <time_frame>For 12 weeks from the date of enrollment of the patient</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Total cholesterol (mg/dl)</measure>
    <time_frame>For 12 weeks from the date of enrollment of the patient</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Triglyceride (TG) (mg/dl)</measure>
    <time_frame>For 12 weeks from the date of enrollment of the patient</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>LDL cholesterol (mg/dl)</measure>
    <time_frame>For 12 weeks from the date of enrollment of the patient</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>HDL cholesterol (mg/dl)</measure>
    <time_frame>For 12 weeks from the date of enrollment of the patient</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">70</enrollment>
  <condition>Non-Alcoholic Fatty Liver Disease</condition>
  <arm_group>
    <arm_group_label>Obeticholic acid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients diagnosed as NAFLD with raised ALT will be treated with both life style modification and Obeticholic acid. Obeticholic acid will be given as 10 mg twice daily. Life style modification includes moderate exercise that is 30 minutes brisk walking a day with dietary advice to avoid fatty foods and excessive sugar containing diet and intake of at least 3 vegetables per day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lifestyle modification</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients diagnosed as NAFLD with raised ALT will be given only life style modification.Life style modification includes moderate exercise that is 30 minutes brisk walking a day with dietary advice to avoid fatty foods and excessive sugar containing diet and intake of at least 3 vegetables per day.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Obeticholic acid</intervention_name>
    <description>Farnesoid X receptor ligand which is a semi synthetic bile acid analogue</description>
    <arm_group_label>Obeticholic acid</arm_group_label>
    <other_name>Life style modification</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  NAFLD (by USG)&#xD;
&#xD;
          -  Raised ALT (&gt;40 U/L)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient with significant alcohol intake (more than 20 gm/day).&#xD;
&#xD;
          -  Patient with history of taking drugs that may cause fatty liver (i.e. tamoxifen,&#xD;
             valproic acid, amiodarone, methotrexate, steroid, OCP) or history of taking drugs that&#xD;
             have shown benefit in previous NASH pilot studies (i.e. vitamin E, metformin,&#xD;
             thiazolidinediones, statin, ARB, fibrates, DPP-4 inhibitor, Omega-3 fatty acid).&#xD;
&#xD;
          -  Chronic viral hepatitis (HBV, HCV).&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Patient with co-morbid condition (COPD, CKD, CCF etc.)&#xD;
&#xD;
          -  Patient with history of recent MI&#xD;
&#xD;
          -  Patient with liver failure&#xD;
&#xD;
          -  Patient with hypothyroidism&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Md F Karim, MBBS,FCPS,MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sir Salimullah Medical College</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Hepatology</name>
      <address>
        <city>Dhaka</city>
        <zip>1000</zip>
        <country>Bangladesh</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bangladesh</country>
  </location_countries>
  <reference>
    <citation>Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF, Chalasani N, Dasarathy S, Diehl AM, Hameed B, Kowdley KV, McCullough A, Terrault N, Clark JM, Tonascia J, Brunt EM, Kleiner DE, Doo E; NASH Clinical Research Network. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015 Mar 14;385(9972):956-65. doi: 10.1016/S0140-6736(14)61933-4. Epub 2014 Nov 7. Erratum In: Lancet. 2015 Mar 14;385(9972):946. Lancet. 2016 Apr 16;387(10028):1618.</citation>
    <PMID>25468160</PMID>
  </reference>
  <reference>
    <citation>Makri E, Cholongitas E, Tziomalos K. Emerging role of obeticholic acid in the management of nonalcoholic fatty liver disease. World J Gastroenterol. 2016 Nov 7;22(41):9039-9043. doi: 10.3748/wjg.v22.i41.9039.</citation>
    <PMID>27895393</PMID>
  </reference>
  <reference>
    <citation>Promrat K, Kleiner DE, Niemeier HM, Jackvony E, Kearns M, Wands JR, Fava JL, Wing RR. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology. 2010 Jan;51(1):121-9. doi: 10.1002/hep.23276.</citation>
    <PMID>19827166</PMID>
  </reference>
  <reference>
    <citation>Kirk E, Reeds DN, Finck BN, Mayurranjan SM, Patterson BW, Klein S. Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction. Gastroenterology. 2009 May;136(5):1552-60. doi: 10.1053/j.gastro.2009.01.048. Epub 2009 Jan 25. Erratum In: Gastroenterology. 2009 Jul;137(1):393. Mayurranjan, Mitra S [corrected to Mayurranjan S Mitra].</citation>
    <PMID>19208352</PMID>
  </reference>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>February 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 11, 2019</study_first_posted>
  <last_update_submitted>May 15, 2022</last_update_submitted>
  <last_update_submitted_qc>May 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 17, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sir Salimullah Medical College Mitford Hospital</investigator_affiliation>
    <investigator_full_name>Md. Fazal Karim</investigator_full_name>
    <investigator_title>Associate Professor</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>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>After completion of the study and statistical analysis, the study report will be published</ipd_description>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>February'2019-June'2019</ipd_time_frame>
    <ipd_access_criteria>drfazalkarim@gmail.com</ipd_access_criteria>
  </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/NCT03836937
org study id: SirSalimullahMCMH
nct id: NCT03836937
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will be conducted upon the patients with fatty liver disease. Patients who will be
      diagnosed as a case of fatty liver disease by ultrasound with raised liver enzyme (ALT) will
      be primarily selected for the study. A total number of 70 patients will be randomly selected
      for the study that will also be divided into two groups for the study purpose. The patients
      will be informed about the details of the study. After getting the detail information those
      who will give informed written consent will be finally included in the study. One group of
      patients will be treated by both life style modification and Obeticholic acid. Another group
      of patients by only life style modification. After 3 months of treatment the two groups will
      be compared of improvement of fatty liver disease and liver enzyme by improvement of
      fibroscan with CAP value as well as improvement of ALT value.
Non-alcoholic fatty liver disease (NAFLD) is an increasingly common cause of chronic liver
      disease worldwide and it is associated with increased liver-related mortality and
      hepatocellular carcinoma, even in the absence of cirrhosis. The prevalence of NAFLD is
      steadily increasing and is currently 20%-30% in Western countries and 5%-18% in Asia. It
      progresses to cirrhosis in 15-20% of affected individuals and is a rising indication for
      liver transplantation. NAFLD is the commonest cause of elevated liver enzymes. Lifestyle
      modifications, including diet and exercise, are imperative for achieving weight loss and
      reducing insulin resistance and hepatic steatosis and inflammation in patients with NAFLD.
      But are suboptimal by long-term adherence in patients with NAFLD. On the other hand, current
      pharmacological treatment of NAFLD has limited efficacy and unfavorable safety profile. In
      this context, obeticholic acid, a selective agonist of the farnesoid X receptors, might
      represent a useful option in these patients. Preclinical studies suggest that obeticholic
      acid improves hepatic steatosis, inflammation and fibrosis. A randomized, placebo-controlled
      Farnesoid X Receptor Ligand Obeticholic Acid in non-alcoholic steatohepatitis Treatment
      (FLINT) trial also showed improvements in liver histology in patients with NAFLD who received
      obeticholic acid. So, there is a need to develop more effective and safe agents for this
      common and life-threatening disease.

      Farnesoid X receptor (FXR) is a member of the nuclear receptor super family expressed in the
      liver, kidney, intestine and adrenal glands. In addition to regulation of bile acid (BA)
      synthesis, several lines of evidence have suggested that FXR plays a role in the
      pathophysiology of NAFLD/NASH. Obeticholic acid is a synthetically modified bile acid that is
      a potent agonist of the farnesoid X nuclear receptor (FXR), a nuclear receptor with major
      effects on bile acid synthesis and transport as well as lipid metabolism and glucose
      homeostasis. Obeticholic acid has been shown to improve serum enzymes in several diseases
      including nonalcoholic fatty liver disease and primary biliary cirrhosis. In FLINT trial
      treatment with obeticholic acid (25 mg/day for 72 weeks) resulted in a highly statistically
      significant improvement in the NAFLD Activity Score of at least two points, with no worsening
      of fibrosis. 45% (50 of 110) of the treated group had this improvement compared with 21% (23
      of 109) of the placebo-treated controls.

      The objective of the study will be to assess the efficacy of obeticholic acid on improvement
      of NAFLD and ALT values in patients with fatty liver disease.

      The study will be conducted in the department of Hepatology, Sir Salimullah Medical College
      and Mitford Hospital. It will be a randomized open label clinical control trial study.
      Patients diagnosed with non-alcoholic fatty liver disease (NAFLD) will be initially targeted
      for the study. Patients who will be diagnosed as a case of NAFLD by ultrasound with raised
      Alanin aminotransferase (ALT) (>40 U/L) will be primarily selected for the study. The total
      sample size will be 70 that will be divided into two groups (Group-A and Group-B) for the
      study purpose. The patients will be informed about the details of the study. After getting
      the detail information, those who will give informed written consent will be finally included
      in the study. A series of baseline investigations including CBC with ESR, fasting blood sugar
      (FBS), 2 hours after 75 g glucose, alanine aminotransferase (ALT), aspartate-aminotransferase
      (AST), gamma-glutamyl transpeptidase (GGT), bilirubin (B), PT with INR, serum albumin, total
      cholesterol (TC) & triglycerides (TG), LDL-C, HDL-C, Thyroid function test will be determined
      on fresh serum using an auto-analyzer. Fibroscan with CAP as well as ALT will be done to
      assess the baseline status of the patients at the time of enrollment of the study. Group-A
      patients will be treated by both life style modification and Obeticholic acid and Group-B
      patients by only life style modification. We shall give 10 mg obeticholic acid twice daily to
      the patients of Group-1. Life style modification including moderate exercise that is 30
      minutes brisk walking a day with dietary advice to avoid fatty foods and excessive sugar
      containing diet and intake of at least 3 vegetables per day will be advised to all the
      patients in both Groups. The patients will be followed for 3 months. Patients will come for
      follow-up after 1 month and finally after 3 months. Each visit will take place between 10.00
      am to 02.00 p.m. & consist with a clinical examination, blood pressure (BP) & body mass index
      (BMI) determinations and a questionnaire. BMI will be computed using the formula: [weight
      (kg)]/ [square of height (meters)]. Serum will be collected for CBC with ESR, FBS, 2 hours
      after 75 g glucose, ALT, AST, PT with INR, serum albumin, GGT, TC, TG, HDL, LDL in first and
      last visit. An alcohol consumption questionnaire will also be administered in each visit and
      study compliance will be strictly monitored. After 3 months of treatment the two groups will
      be compared of improvement of NAFLD and liver enzyme by improvement of fibroscan with CAP
      value as well as improvement of ALT value with the baseline ALT and fibroscan with CAP
      values.

      All Data will be presented as mean ± SD & analyzed by SPSS (version 23). Qualitative data
      will be analyzed by Chi-square test & quantitative data will be analyzed by student's t-test.
      A statistically significant result will be considered when P value < 0.05.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Open label randomized clinical control trial study
primary purpose: Treatment
masking: None (Open Label)
measure: Change in fibroscan score (Kpa) and CAP value (Kpa) which signifies fibrosis and steatosis status respectively.
time frame: For 12 weeks from the date of enrollment of the patient.
description: Obeticholic acid and life style modification improve fibroscan with CAP results in patients with NAFLD.
Change in symptoms after 12 weeks of treatment or life style modification.
Change in liver function test, fibroscan values and CAP values after treatment or life style modification.
measure: Change in BMI (weight in kg/height in meter square)
time frame: For 12 weeks from the date of enrollment of the patient.
measure: Change in ALT (U/L)
time frame: For 12 weeks from the date of enrollment of the patient.
measure: Fasting blood sugar (FBS) (mmol/L)
time frame: For 12 weeks from the date of enrollment of the patient.
measure: 2 hours after 75 gm glucose (mmol/L)
time frame: For 12 weeks from the date of enrollment of the patient
measure: Serum bilirubin (mg/dl)
time frame: For 12 weeks from the date of enrollment of the patient
measure: Aspertate aminotransferase (AST) (U/L)
time frame: For 12 weeks from the date of enrollment of the patient
measure: Gamma glutamyle transpeptidase (GGT) (U/L)
time frame: For 12 weeks from the date of enrollment of the patient
measure: Serum albumin (gm/dl)
time frame: For 12 weeks from the date of enrollment of the patient
measure: Prothrombin time (PT) (sec)
time frame: For 12 weeks from the date of enrollment of the patient
measure: Total cholesterol (mg/dl)
time frame: For 12 weeks from the date of enrollment of the patient
measure: Triglyceride (TG) (mg/dl)
time frame: For 12 weeks from the date of enrollment of the patient
measure: LDL cholesterol (mg/dl)
time frame: For 12 weeks from the date of enrollment of the patient
measure: HDL cholesterol (mg/dl)
time frame: For 12 weeks from the date of enrollment of the patient
arm group label: Obeticholic acid
arm group type: Experimental
description: Patients diagnosed as NAFLD with raised ALT will be treated with both life style modification and Obeticholic acid. Obeticholic acid will be given as 10 mg twice daily. Life style modification includes moderate exercise that is 30 minutes brisk walking a day with dietary advice to avoid fatty foods and excessive sugar containing diet and intake of at least 3 vegetables per day.
arm group label: Lifestyle modification
arm group type: No Intervention
description: Patients diagnosed as NAFLD with raised ALT will be given only life style modification.Life style modification includes moderate exercise that is 30 minutes brisk walking a day with dietary advice to avoid fatty foods and excessive sugar containing diet and intake of at least 3 vegetables per day.
intervention type: Drug
intervention name: Obeticholic acid
description: Farnesoid X receptor ligand which is a semi synthetic bile acid analogue
arm group label: Obeticholic acid
other name: Life style modification
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Md F Karim, MBBS,FCPS,MD
role: Principal Investigator
affiliation: Sir Salimullah Medical College
facility: 
country: Bangladesh
citation: Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF, Chalasani N, Dasarathy S, Diehl AM, Hameed B, Kowdley KV, McCullough A, Terrault N, Clark JM, Tonascia J, Brunt EM, Kleiner DE, Doo E; NASH Clinical Research Network. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015 Mar 14;385(9972):956-65. doi: 10.1016/S0140-6736(14)61933-4. Epub 2014 Nov 7. Erratum In: Lancet. 2015 Mar 14;385(9972):946. Lancet. 2016 Apr 16;387(10028):1618.
PMID: 25468160
citation: Makri E, Cholongitas E, Tziomalos K. Emerging role of obeticholic acid in the management of nonalcoholic fatty liver disease. World J Gastroenterol. 2016 Nov 7;22(41):9039-9043. doi: 10.3748/wjg.v22.i41.9039.
PMID: 27895393
citation: Promrat K, Kleiner DE, Niemeier HM, Jackvony E, Kearns M, Wands JR, Fava JL, Wing RR. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology. 2010 Jan;51(1):121-9. doi: 10.1002/hep.23276.
PMID: 19827166
citation: Kirk E, Reeds DN, Finck BN, Mayurranjan SM, Patterson BW, Klein S. Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction. Gastroenterology. 2009 May;136(5):1552-60. doi: 10.1053/j.gastro.2009.01.048. Epub 2009 Jan 25. Erratum In: Gastroenterology. 2009 Jul;137(1):393. Mayurranjan, Mitra S [corrected to Mayurranjan S Mitra].
PMID: 19208352
responsible party type: Principal Investigator
investigator affiliation: Sir Salimullah Medical College Mitford Hospital
investigator full name: Md. Fazal Karim
investigator title: Associate Professor
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
sharing ipd: Yes
ipd description: After completion of the study and statistical analysis, the study report will be published
ipd info type: Clinical Study Report (CSR)
ipd time frame: February'2019-June'2019
ipd access criteria: drfazalkarim@gmail.com