<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/NCT03294850</url>
  </required_header>
  <id_info>
    <org_study_id>TRIMDFH 1000376</org_study_id>
    <nct_id>NCT03294850</nct_id>
  </id_info>
  <brief_title>Biomarkers of Liver Pathology in Patients With Presumed Non-Alcoholic Steatohepatitis Following Bariatric Surgery</brief_title>
  <acronym>BARI</acronym>
  <official_title>Evaluation of Biomarkers to Quantify Liver Pathology in Patients With Presumed Non-Alcoholic Steatohepatitis at Baseline and Following Bariatric Surgery (BARI)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AdventHealth Translational Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AdventHealth Translational Research Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate imaging and other biomarkers of non-alcoholic fatty&#xD;
      liver disease before and after bariatric surgery.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 18, 2018</start_date>
  <completion_date type="Actual">September 11, 2020</completion_date>
  <primary_completion_date type="Actual">November 14, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent Change in Liver Fat Between Baseline and 12 Weeks Post-surgery</measure>
    <time_frame>12 weeks</time_frame>
    <description>Assessed by magnetic resonance imaging proton density fat fraction (MRI PDFF)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percent Change in Liver Stiffness Between Baseline and12 Weeks Post-surgery</measure>
    <time_frame>12 weeks</time_frame>
    <description>We will evaluate change in liver stiffness, a surrogate for fibrosis, as assessed by magnetic resonance elastography (MRE)</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>NASH - Nonalcoholic Steatohepatitis; NAFLD - Nonalcoholic Fatty Liver Disease</condition>
  <arm_group>
    <arm_group_label>NASH group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>These are individuals that have been identified as having NASH by MRE. Confirmation with liver biopsy required for continuation in the longitudinal study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-NASH (NAFLD or normal) group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>These are individuals that do not have NASH. They either have normal liver physiology or only have evidence of hepatic steatosis. This group will be studied up until the day of their bariatric surgery and will serve as a comparator population with respect to baseline measurements.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Bariatric surgery</intervention_name>
    <description>Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied</description>
    <arm_group_label>NASH group</arm_group_label>
    <arm_group_label>Non-NASH (NAFLD or normal) group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>HepQuant SHUNT Dual Cholate Liver Diagnostic Kit</intervention_name>
    <description>For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function.</description>
    <arm_group_label>NASH group</arm_group_label>
    <arm_group_label>Non-NASH (NAFLD or normal) group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥18 years&#xD;
&#xD;
          -  Undergoing bariatric surgery (Roux-en-Y or gastric sleeve only) as part of clinical&#xD;
             care.&#xD;
&#xD;
          -  Negative human chorionic gonadotropin (hCG) level (female participants who become&#xD;
             pregnant during the study will be withdrawn)&#xD;
&#xD;
          -  For nonalcoholic steatohepatitis (NASH) participants - FibroScan: Controlled&#xD;
             Attenuation Parameter (CAP) 290 db/m and Vibration-Controlled Transient Elastography&#xD;
             (VCTE) 8 kilopascal (kPa). For participants who meet FibroScan criteria, inclusion&#xD;
             will require MRI-PDFF ≥8%; MRE: ≥2.7 kPa.&#xD;
&#xD;
          -  For NAFLD or normal participants - FibroScan: No requirement for minimum CAP level and&#xD;
             VCTE &lt;7 kPa. For participants that meet the FibroScan criteria- no requirement for&#xD;
             minimum MRI-PDFF; MRE ≤ 2 kPa.&#xD;
&#xD;
          -  Histopathology assessment of liver biopsy that confirms NASH diagnosis&#xD;
&#xD;
          -  Hemoglobin A1c (HbA1c) ≤ 9.5%&#xD;
&#xD;
          -  Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)&#xD;
&#xD;
          -  Body mass index (BMI) ≥ 35 kg/m2&#xD;
&#xD;
          -  Able to speak and understand written and spoken English&#xD;
&#xD;
          -  Understands the procedures and agrees to participate by giving written informed&#xD;
             consent&#xD;
&#xD;
          -  Willing and able to comply with scheduled visits, laboratory tests, and other study&#xD;
             procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participation in other studies involving investigational drug(s) within 30 days prior&#xD;
             to Screening Visit 1&#xD;
&#xD;
          -  History of regular alcohol consumption exceeding 14 drinks/week for females or 21&#xD;
             drinks/week for males within the previous 6 months&#xD;
&#xD;
          -  A total score of 8 on the Alcohol Use Disorders Identification Test questionnaire&#xD;
             (Appendix B), indicating harmful or hazardous ethanol consumption&#xD;
&#xD;
          -  A positive urine drug test for illicit drugs&#xD;
&#xD;
          -  Clinical evidence of hepatic decompensation, including, but not limited to esophageal&#xD;
             varices, ascites, or hepatic encephalopathy&#xD;
&#xD;
          -  Evidence of other forms of chronic liver disease (including laboratory tests as&#xD;
             assessed by a sponsor-identified laboratory, and confirmed with a single repeat, if&#xD;
             needed): Hepatitis B virus (HBV): defined by presence of hepatitis B surface antigen&#xD;
             (HBsAg); Hepatitis C virus (HCV): As defined by a clinical history of previous&#xD;
             diagnosis of Hepatitis C (treated or untreated) or a positive Hepatitis C antibody&#xD;
             (HCVAb); Known diagnosis of primary biliary cirrhosis, primary sclerosing cholangitis,&#xD;
             autoimmune hepatitis, or overlap syndrome; Alcoholic liver disease; Known diagnosis of&#xD;
             hemochromatosis; Prior known drug-induced liver injury; Known or suspected&#xD;
             hepatocellular carcinoma (HCC) or other liver cancer; History of liver transplant,&#xD;
             current placement on a liver transplant list, or current model of end-stage liver&#xD;
             disease (MELD) score &gt;12; Histological presence of cirrhosis on a prior biopsy.&#xD;
&#xD;
          -  Human Immunodeficiency Virus (HIV) infection, defined as presence of HIV antibody&#xD;
&#xD;
          -  Diagnosis of type 1 diabetes mellitus&#xD;
&#xD;
          -  Any malignancy not considered cured, except basal cell carcinoma and squamous cell&#xD;
             carcinoma of the skin (a subject is considered cured if there has been no evidence of&#xD;
             cancer recurrence in the previous 5 years)&#xD;
&#xD;
          -  Use of drugs historically associated with non-alcoholic fatty liver disease (NAFLD)&#xD;
             for 1 month in the previous year prior to Visit 3 (day of Surgery); examples include:&#xD;
             amiodarone, methotrexate, systemic glucocorticoids, tetracyclines, tamoxifen,&#xD;
             estrogens at doses greater than those used for hormone replacement, anabolic steroids,&#xD;
             valproic acid, other known hepatotoxins&#xD;
&#xD;
          -  Subjects with history of severe claustrophobia impacting ability to perform MRI during&#xD;
             the study without mild sedation/treatment with an anxiolytic&#xD;
&#xD;
          -  Subjects who fulfill any of the contraindications for MRI; examples include metal&#xD;
             implants, devices, paramagnetic objects contained within the body and excessive or&#xD;
             metal-containing tattoos&#xD;
&#xD;
          -  Unable to participate in MR assessments due to physical limitations of equipment&#xD;
             tolerances (MRI bore size and 500-pound weight limit) based on Investigator's judgment&#xD;
             at screening&#xD;
&#xD;
          -  Any person unable to lie still within the environment of the MRI scanner or maintain a&#xD;
             breath hold for the required period to acquire images without mild sedation/treatment&#xD;
             with an anxiolytic&#xD;
&#xD;
          -  Subjects with any anatomical or pathological abnormality that would either preclude or&#xD;
             tend to confound the analysis of study data, including any clinically significant&#xD;
             abnormal findings on the MRI obtained at Screening Visit 2.&#xD;
&#xD;
          -  Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more&#xD;
             within 56 days prior to Screening Visit 1 (participants may not donate blood any time&#xD;
             during the study, through the final study visit)&#xD;
&#xD;
          -  Known history or suspected hypersensitivity to human serum albumin, or its&#xD;
             preparations.&#xD;
&#xD;
          -  Investigator site staff members directly involved in the conduct of the study and&#xD;
             their family members, site staff members otherwise supervised by the investigator, or&#xD;
             subjects who are Pfizer employees, including their family members, directly involved&#xD;
             in the conduct of the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steven Smith, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Study Principal Investigator</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Translational Research Institute for Metabolism and Diabetes</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.tri-md.org</url>
    <description>Translational Research Institute for Metabolism and Diabetes</description>
  </link>
  <reference>
    <citation>Ahmed MH, Abu EO, Byrne CD. Non-Alcoholic Fatty Liver Disease (NAFLD): new challenge for general practitioners and important burden for health authorities? Prim Care Diabetes. 2010 Oct;4(3):129-37. doi: 10.1016/j.pcd.2010.02.004. Epub 2010 Mar 17.</citation>
    <PMID>20299294</PMID>
  </reference>
  <reference>
    <citation>Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol. 2013 Nov;10(11):686-90. doi: 10.1038/nrgastro.2013.171. Epub 2013 Sep 17.</citation>
    <PMID>24042449</PMID>
  </reference>
  <reference>
    <citation>Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011 Aug;34(3):274-85. doi: 10.1111/j.1365-2036.2011.04724.x. Epub 2011 May 30.</citation>
    <PMID>21623852</PMID>
  </reference>
  <reference>
    <citation>Sanyal AJ, Friedman SL, McCullough AJ, Dimick-Santos L; American Association for the Study of Liver Diseases; United States Food and Drug Administration. Challenges and opportunities in drug and biomarker development for nonalcoholic steatohepatitis: findings and recommendations from an American Association for the Study of Liver Diseases-U.S. Food and Drug Administration Joint Workshop. Hepatology. 2015 Apr;61(4):1392-405. doi: 10.1002/hep.27678. Epub 2015 Mar 19.</citation>
    <PMID>25557690</PMID>
  </reference>
  <reference>
    <citation>Cohen JC, Horton JD, Hobbs HH. Human fatty liver disease: old questions and new insights. Science. 2011 Jun 24;332(6037):1519-23. doi: 10.1126/science.1204265.</citation>
    <PMID>21700865</PMID>
  </reference>
  <reference>
    <citation>Ratziu V, Charlotte F, Heurtier A, Gombert S, Giral P, Bruckert E, Grimaldi A, Capron F, Poynard T; LIDO Study Group. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology. 2005 Jun;128(7):1898-906. doi: 10.1053/j.gastro.2005.03.084.</citation>
    <PMID>15940625</PMID>
  </reference>
  <reference>
    <citation>Alkhouri N, McCullough AJ. Noninvasive Diagnosis of NASH and Liver Fibrosis Within the Spectrum of NAFLD. Gastroenterol Hepatol (N Y). 2012 Oct;8(10):661-8.</citation>
    <PMID>24683373</PMID>
  </reference>
  <reference>
    <citation>Papagianni M, Sofogianni A, Tziomalos K. Non-invasive methods for the diagnosis of nonalcoholic fatty liver disease. World J Hepatol. 2015 Apr 8;7(4):638-48. doi: 10.4254/wjh.v7.i4.638.</citation>
    <PMID>25866601</PMID>
  </reference>
  <reference>
    <citation>Dulai PS, Sirlin CB, Loomba R. MRI and MRE for non-invasive quantitative assessment of hepatic steatosis and fibrosis in NAFLD and NASH: Clinical trials to clinical practice. J Hepatol. 2016 Nov;65(5):1006-1016. doi: 10.1016/j.jhep.2016.06.005. Epub 2016 Jun 14.</citation>
    <PMID>27312947</PMID>
  </reference>
  <reference>
    <citation>Hashemi SA, Alavian SM, Gholami-Fesharaki M. Assessment of transient elastography (FibroScan) for diagnosis of fibrosis in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Caspian J Intern Med. 2016 Fall;7(4):242-252.</citation>
    <PMID>27999641</PMID>
  </reference>
  <reference>
    <citation>Barker KB, Palekar NA, Bowers SP, Goldberg JE, Pulcini JP, Harrison SA. Non-alcoholic steatohepatitis: effect of Roux-en-Y gastric bypass surgery. Am J Gastroenterol. 2006 Feb;101(2):368-73. doi: 10.1111/j.1572-0241.2006.00419.x.</citation>
    <PMID>16454845</PMID>
  </reference>
  <reference>
    <citation>Rabl C, Campos GM. The impact of bariatric surgery on nonalcoholic steatohepatitis. Semin Liver Dis. 2012 Feb;32(1):80-91. doi: 10.1055/s-0032-1306428. Epub 2012 Mar 13.</citation>
    <PMID>22418890</PMID>
  </reference>
  <reference>
    <citation>Hafeez S, Ahmed MH. Bariatric surgery as potential treatment for nonalcoholic fatty liver disease: a future treatment by choice or by chance? J Obes. 2013;2013:839275. doi: 10.1155/2013/839275. Epub 2013 Jan 29.</citation>
    <PMID>23431426</PMID>
  </reference>
  <reference>
    <citation>Schneck AS, Anty R, Patouraux S, Bonnafous S, Rousseau D, Lebeaupin C, Bailly-Maitre B, Sans A, Tran A, Gugenheim J, Iannelli A, Gual P. Roux-En Y Gastric Bypass Results in Long-Term Remission of Hepatocyte Apoptosis and Hepatic Histological Features of Non-alcoholic Steatohepatitis. Front Physiol. 2016 Aug 19;7:344. doi: 10.3389/fphys.2016.00344. eCollection 2016.</citation>
    <PMID>27594839</PMID>
  </reference>
  <reference>
    <citation>Alizai PH, Wendl J, Roeth AA, Klink CD, Luedde T, Steinhoff I, Neumann UP, Schmeding M, Ulmer F. Functional Liver Recovery After Bariatric Surgery--a Prospective Cohort Study with the LiMAx Test. Obes Surg. 2015 Nov;25(11):2047-53. doi: 10.1007/s11695-015-1664-0.</citation>
    <PMID>25869925</PMID>
  </reference>
  <reference>
    <citation>Barr J, Caballeria J, Martinez-Arranz I, Dominguez-Diez A, Alonso C, Muntane J, Perez-Cormenzana M, Garcia-Monzon C, Mayo R, Martin-Duce A, Romero-Gomez M, Lo Iacono O, Tordjman J, Andrade RJ, Perez-Carreras M, Le Marchand-Brustel Y, Tran A, Fernandez-Escalante C, Arevalo E, Garcia-Unzueta M, Clement K, Crespo J, Gual P, Gomez-Fleitas M, Martinez-Chantar ML, Castro A, Lu SC, Vazquez-Chantada M, Mato JM. Obesity-dependent metabolic signatures associated with nonalcoholic fatty liver disease progression. J Proteome Res. 2012 Apr 6;11(4):2521-32. doi: 10.1021/pr201223p. Epub 2012 Mar 15.</citation>
    <PMID>22364559</PMID>
  </reference>
  <reference>
    <citation>Nielsen MJ, Nedergaard AF, Sun S, Veidal SS, Larsen L, Zheng Q, Suetta C, Henriksen K, Christiansen C, Karsdal MA, Leeming DJ. The neo-epitope specific PRO-C3 ELISA measures true formation of type III collagen associated with liver and muscle parameters. Am J Transl Res. 2013 Apr 19;5(3):303-15. Print 2013.</citation>
    <PMID>23634241</PMID>
  </reference>
  <reference>
    <citation>Nielsen MJ, Veidal SS, Karsdal MA, Orsnes-Leeming DJ, Vainer B, Gardner SD, Hamatake R, Goodman ZD, Schuppan D, Patel K. Plasma Pro-C3 (N-terminal type III collagen propeptide) predicts fibrosis progression in patients with chronic hepatitis C. Liver Int. 2015 Feb;35(2):429-37. doi: 10.1111/liv.12700. Epub 2014 Oct 29.</citation>
    <PMID>25308921</PMID>
  </reference>
  <reference>
    <citation>Helmke S, Colmenero J, Everson GT. Noninvasive assessment of liver function. Curr Opin Gastroenterol. 2015 May;31(3):199-208. doi: 10.1097/MOG.0000000000000167.</citation>
    <PMID>25714706</PMID>
  </reference>
  <reference>
    <citation>Schnabl B, Brenner DA. Interactions between the intestinal microbiome and liver diseases. Gastroenterology. 2014 May;146(6):1513-24. doi: 10.1053/j.gastro.2014.01.020. Epub 2014 Jan 15.</citation>
    <PMID>24440671</PMID>
  </reference>
  <reference>
    <citation>Bonder A, Afdhal N. Utilization of FibroScan in clinical practice. Curr Gastroenterol Rep. 2014 Feb;16(2):372. doi: 10.1007/s11894-014-0372-6.</citation>
    <PMID>24452634</PMID>
  </reference>
  <reference>
    <citation>Chen J, Talwalkar JA, Yin M, Glaser KJ, Sanderson SO, Ehman RL. Early detection of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease by using MR elastography. Radiology. 2011 Jun;259(3):749-56. doi: 10.1148/radiol.11101942. Epub 2011 Apr 1.</citation>
    <PMID>21460032</PMID>
  </reference>
  <reference>
    <citation>Thomas MS, Newman D, Leinhard OD, Kasmai B, Greenwood R, Malcolm PN, Karlsson A, Rosander J, Borga M, Toms AP. Test-retest reliability of automated whole body and compartmental muscle volume measurements on a wide bore 3T MR system. Eur Radiol. 2014 Sep;24(9):2279-91. doi: 10.1007/s00330-014-3226-6. Epub 2014 May 29.</citation>
    <PMID>24871333</PMID>
  </reference>
  <reference>
    <citation>Karlsson A, Rosander J, Romu T, Tallberg J, Gronqvist A, Borga M, Dahlqvist Leinhard O. Automatic and quantitative assessment of regional muscle volume by multi-atlas segmentation using whole-body water-fat MRI. J Magn Reson Imaging. 2015 Jun;41(6):1558-69. doi: 10.1002/jmri.24726. Epub 2014 Aug 11.</citation>
    <PMID>25111561</PMID>
  </reference>
  <reference>
    <citation>West J, Dahlqvist Leinhard O, Romu T, Collins R, Garratt S, Bell JD, Borga M, Thomas L. Feasibility of MR-Based Body Composition Analysis in Large Scale Population Studies. PLoS One. 2016 Sep 23;11(9):e0163332. doi: 10.1371/journal.pone.0163332. eCollection 2016.</citation>
    <PMID>27662190</PMID>
  </reference>
  <reference>
    <citation>Banerjee R, Pavlides M, Tunnicliffe EM, Piechnik SK, Sarania N, Philips R, Collier JD, Booth JC, Schneider JE, Wang LM, Delaney DW, Fleming KA, Robson MD, Barnes E, Neubauer S. Multiparametric magnetic resonance for the non-invasive diagnosis of liver disease. J Hepatol. 2014 Jan;60(1):69-77. doi: 10.1016/j.jhep.2013.09.002. Epub 2013 Sep 12.</citation>
    <PMID>24036007</PMID>
  </reference>
  <reference>
    <citation>Pavlides M, Banerjee R, Sellwood J, Kelly CJ, Robson MD, Booth JC, Collier J, Neubauer S, Barnes E. Multiparametric magnetic resonance imaging predicts clinical outcomes in patients with chronic liver disease. J Hepatol. 2016 Feb;64(2):308-315. doi: 10.1016/j.jhep.2015.10.009. Epub 2015 Nov 10.</citation>
    <PMID>26471505</PMID>
  </reference>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>September 22, 2017</study_first_submitted>
  <study_first_submitted_qc>September 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 27, 2017</study_first_posted>
  <results_first_submitted>May 18, 2021</results_first_submitted>
  <results_first_submitted_qc>May 18, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 14, 2021</results_first_posted>
  <last_update_submitted>July 14, 2021</last_update_submitted>
  <last_update_submitted_qc>July 14, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cholic Acids</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 24, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/50/NCT03294850/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Recruitment began 7/18/2018 and concluded 12/3/2019. Participants were recruited from a local bariatric surgery medical practice.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>NASH Group</title>
          <description>These are individuals that have been identified as having NASH by MRE. Confirmation with liver biopsy required for continuation in the longitudinal study.&#xD;
Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied&#xD;
HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function.</description>
        </group>
        <group group_id="P2">
          <title>Non-NASH (NAFLD or Normal) Group</title>
          <description>These are individuals that do not have NASH. They either have normal liver physiology or only have evidence of hepatic steatosis. This group will be studied up until the day of their bariatric surgery and will serve as a comparator population with respect to baseline measurements.&#xD;
Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied&#xD;
HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>NASH Group</title>
          <description>These are individuals that have been identified as having NASH by MRE. Confirmation with liver biopsy required for continuation in the longitudinal study.&#xD;
Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied&#xD;
HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function.</description>
        </group>
        <group group_id="B2">
          <title>Non-NASH (NAFLD or Normal) Group</title>
          <description>These are individuals that do not have NASH. They either have normal liver physiology or only have evidence of hepatic steatosis. This group will be studied up until the day of their bariatric surgery and will serve as a comparator population with respect to baseline measurements.&#xD;
Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied&#xD;
HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="4"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="14"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40.750" spread="6.551"/>
                    <measurement group_id="B2" value="38.600" spread="9.119"/>
                    <measurement group_id="B3" value="39.21" spread="8.276"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percent Change in Liver Fat Between Baseline and 12 Weeks Post-surgery</title>
        <description>Assessed by magnetic resonance imaging proton density fat fraction (MRI PDFF)</description>
        <time_frame>12 weeks</time_frame>
        <population>Only the NASH group had longitudinal evaluation</population>
        <group_list>
          <group group_id="O1">
            <title>NASH Group</title>
            <description>These are individuals that have been identified as having NASH by MRE. Confirmation with liver biopsy required for continuation in the longitudinal study.&#xD;
Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied&#xD;
HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function.</description>
          </group>
          <group group_id="O2">
            <title>Non-NASH (NAFLD or Normal) Group</title>
            <description>These are individuals that do not have NASH. They either have normal liver physiology or only have evidence of hepatic steatosis. This group will be studied up until the day of their bariatric surgery and will serve as a comparator population with respect to baseline measurements.&#xD;
Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied&#xD;
HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Liver Fat Between Baseline and 12 Weeks Post-surgery</title>
          <description>Assessed by magnetic resonance imaging proton density fat fraction (MRI PDFF)</description>
          <population>Only the NASH group had longitudinal evaluation</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-16.4" spread="52.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percent Change in Liver Stiffness Between Baseline and12 Weeks Post-surgery</title>
        <description>We will evaluate change in liver stiffness, a surrogate for fibrosis, as assessed by magnetic resonance elastography (MRE)</description>
        <time_frame>12 weeks</time_frame>
        <population>Only NASH group had longitudinal evaluation</population>
        <group_list>
          <group group_id="O1">
            <title>NASH Group</title>
            <description>These are individuals that have been identified as having NASH by MRE. Confirmation with liver biopsy required for continuation in the longitudinal study.&#xD;
Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied&#xD;
HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function.</description>
          </group>
          <group group_id="O2">
            <title>Non-NASH (NAFLD or Normal) Group</title>
            <description>These are individuals that do not have NASH. They either have normal liver physiology or only have evidence of hepatic steatosis. This group will be studied up until the day of their bariatric surgery and will serve as a comparator population with respect to baseline measurements.&#xD;
Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied&#xD;
HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Liver Stiffness Between Baseline and12 Weeks Post-surgery</title>
          <description>We will evaluate change in liver stiffness, a surrogate for fibrosis, as assessed by magnetic resonance elastography (MRE)</description>
          <population>Only NASH group had longitudinal evaluation</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.9" spread="10.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>2.22 years</time_frame>
      <group_list>
        <group group_id="E1">
          <title>NASH Group</title>
          <description>These are individuals that have been identified as having NASH by MRE. Confirmation with liver biopsy required for continuation in the longitudinal study.&#xD;
Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied&#xD;
HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function.</description>
        </group>
        <group group_id="E2">
          <title>Non-NASH (NAFLD or Normal) Group</title>
          <description>These are individuals that do not have NASH. They either have normal liver physiology or only have evidence of hepatic steatosis. This group will be studied up until the day of their bariatric surgery and will serve as a comparator population with respect to baseline measurements.&#xD;
Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied&#xD;
HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Worsening Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gas Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>H. Pylori Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Inactive mild gastritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Shingles</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infections</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Vitamin D Defficiency</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Bruising, tenderness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Lower Leg Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Right Arm Tenderness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Cyst in pituitaty</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pleural Effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Sinus Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>This trial was limited by the need to close the trial prior to enrolling all participants due to extreme difficulties with recruitment. Based on our power estimates, we needed 25 people in the NASH group, and we were only able to enroll 4. Therefore, our analyses will be limited the basic plans proposed in the protocol and will likely be exploratory and hypothesis generating in nature.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Karen Corbin</name_or_title>
      <organization>AdventHealth Translational Research Institute</organization>
      <phone>(407) 303-7100</phone>
      <email>Karen.Corbin@AdventHealth.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03294850
org study id: TRIMDFH 1000376
nct id: NCT03294850
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
The purpose of this study is to evaluate imaging and other biomarkers of non-alcoholic fatty
      liver disease before and after bariatric surgery.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Percent Change in Liver Fat Between Baseline and 12 Weeks Post-surgery
time frame: 12 weeks
description: Assessed by magnetic resonance imaging proton density fat fraction (MRI PDFF)
measure: Percent Change in Liver Stiffness Between Baseline and12 Weeks Post-surgery
time frame: 12 weeks
description: We will evaluate change in liver stiffness, a surrogate for fibrosis, as assessed by magnetic resonance elastography (MRE)
arm group label: NASH group
arm group type: Experimental
description: These are individuals that have been identified as having NASH by MRE. Confirmation with liver biopsy required for continuation in the longitudinal study.
arm group label: Non-NASH (NAFLD or normal) group
arm group type: Active Comparator
description: These are individuals that do not have NASH. They either have normal liver physiology or only have evidence of hepatic steatosis. This group will be studied up until the day of their bariatric surgery and will serve as a comparator population with respect to baseline measurements.
intervention type: Procedure
intervention name: Bariatric surgery
description: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied
arm group label: NASH group
arm group label: Non-NASH (NAFLD or normal) group
intervention type: Device
intervention name: HepQuant SHUNT Dual Cholate Liver Diagnostic Kit
description: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function.
arm group label: NASH group
arm group label: Non-NASH (NAFLD or normal) group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Steven Smith, MD
role: Principal Investigator
affiliation: Study Principal Investigator
facility: 
country: United States
url: http://www.tri-md.org
description: Translational Research Institute for Metabolism and Diabetes
citation: Ahmed MH, Abu EO, Byrne CD. Non-Alcoholic Fatty Liver Disease (NAFLD): new challenge for general practitioners and important burden for health authorities? Prim Care Diabetes. 2010 Oct;4(3):129-37. doi: 10.1016/j.pcd.2010.02.004. Epub 2010 Mar 17.
PMID: 20299294
citation: Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol. 2013 Nov;10(11):686-90. doi: 10.1038/nrgastro.2013.171. Epub 2013 Sep 17.
PMID: 24042449
citation: Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011 Aug;34(3):274-85. doi: 10.1111/j.1365-2036.2011.04724.x. Epub 2011 May 30.
PMID: 21623852
citation: Sanyal AJ, Friedman SL, McCullough AJ, Dimick-Santos L; American Association for the Study of Liver Diseases; United States Food and Drug Administration. Challenges and opportunities in drug and biomarker development for nonalcoholic steatohepatitis: findings and recommendations from an American Association for the Study of Liver Diseases-U.S. Food and Drug Administration Joint Workshop. Hepatology. 2015 Apr;61(4):1392-405. doi: 10.1002/hep.27678. Epub 2015 Mar 19.
PMID: 25557690
citation: Cohen JC, Horton JD, Hobbs HH. Human fatty liver disease: old questions and new insights. Science. 2011 Jun 24;332(6037):1519-23. doi: 10.1126/science.1204265.
PMID: 21700865
citation: Ratziu V, Charlotte F, Heurtier A, Gombert S, Giral P, Bruckert E, Grimaldi A, Capron F, Poynard T; LIDO Study Group. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology. 2005 Jun;128(7):1898-906. doi: 10.1053/j.gastro.2005.03.084.
PMID: 15940625
citation: Alkhouri N, McCullough AJ. Noninvasive Diagnosis of NASH and Liver Fibrosis Within the Spectrum of NAFLD. Gastroenterol Hepatol (N Y). 2012 Oct;8(10):661-8.
PMID: 24683373
citation: Papagianni M, Sofogianni A, Tziomalos K. Non-invasive methods for the diagnosis of nonalcoholic fatty liver disease. World J Hepatol. 2015 Apr 8;7(4):638-48. doi: 10.4254/wjh.v7.i4.638.
PMID: 25866601
citation: Dulai PS, Sirlin CB, Loomba R. MRI and MRE for non-invasive quantitative assessment of hepatic steatosis and fibrosis in NAFLD and NASH: Clinical trials to clinical practice. J Hepatol. 2016 Nov;65(5):1006-1016. doi: 10.1016/j.jhep.2016.06.005. Epub 2016 Jun 14.
PMID: 27312947
citation: Hashemi SA, Alavian SM, Gholami-Fesharaki M. Assessment of transient elastography (FibroScan) for diagnosis of fibrosis in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Caspian J Intern Med. 2016 Fall;7(4):242-252.
PMID: 27999641
citation: Barker KB, Palekar NA, Bowers SP, Goldberg JE, Pulcini JP, Harrison SA. Non-alcoholic steatohepatitis: effect of Roux-en-Y gastric bypass surgery. Am J Gastroenterol. 2006 Feb;101(2):368-73. doi: 10.1111/j.1572-0241.2006.00419.x.
PMID: 16454845
citation: Rabl C, Campos GM. The impact of bariatric surgery on nonalcoholic steatohepatitis. Semin Liver Dis. 2012 Feb;32(1):80-91. doi: 10.1055/s-0032-1306428. Epub 2012 Mar 13.
PMID: 22418890
citation: Hafeez S, Ahmed MH. Bariatric surgery as potential treatment for nonalcoholic fatty liver disease: a future treatment by choice or by chance? J Obes. 2013;2013:839275. doi: 10.1155/2013/839275. Epub 2013 Jan 29.
PMID: 23431426
citation: Schneck AS, Anty R, Patouraux S, Bonnafous S, Rousseau D, Lebeaupin C, Bailly-Maitre B, Sans A, Tran A, Gugenheim J, Iannelli A, Gual P. Roux-En Y Gastric Bypass Results in Long-Term Remission of Hepatocyte Apoptosis and Hepatic Histological Features of Non-alcoholic Steatohepatitis. Front Physiol. 2016 Aug 19;7:344. doi: 10.3389/fphys.2016.00344. eCollection 2016.
PMID: 27594839
citation: Alizai PH, Wendl J, Roeth AA, Klink CD, Luedde T, Steinhoff I, Neumann UP, Schmeding M, Ulmer F. Functional Liver Recovery After Bariatric Surgery--a Prospective Cohort Study with the LiMAx Test. Obes Surg. 2015 Nov;25(11):2047-53. doi: 10.1007/s11695-015-1664-0.
PMID: 25869925
citation: Barr J, Caballeria J, Martinez-Arranz I, Dominguez-Diez A, Alonso C, Muntane J, Perez-Cormenzana M, Garcia-Monzon C, Mayo R, Martin-Duce A, Romero-Gomez M, Lo Iacono O, Tordjman J, Andrade RJ, Perez-Carreras M, Le Marchand-Brustel Y, Tran A, Fernandez-Escalante C, Arevalo E, Garcia-Unzueta M, Clement K, Crespo J, Gual P, Gomez-Fleitas M, Martinez-Chantar ML, Castro A, Lu SC, Vazquez-Chantada M, Mato JM. Obesity-dependent metabolic signatures associated with nonalcoholic fatty liver disease progression. J Proteome Res. 2012 Apr 6;11(4):2521-32. doi: 10.1021/pr201223p. Epub 2012 Mar 15.
PMID: 22364559
citation: Nielsen MJ, Nedergaard AF, Sun S, Veidal SS, Larsen L, Zheng Q, Suetta C, Henriksen K, Christiansen C, Karsdal MA, Leeming DJ. The neo-epitope specific PRO-C3 ELISA measures true formation of type III collagen associated with liver and muscle parameters. Am J Transl Res. 2013 Apr 19;5(3):303-15. Print 2013.
PMID: 23634241
citation: Nielsen MJ, Veidal SS, Karsdal MA, Orsnes-Leeming DJ, Vainer B, Gardner SD, Hamatake R, Goodman ZD, Schuppan D, Patel K. Plasma Pro-C3 (N-terminal type III collagen propeptide) predicts fibrosis progression in patients with chronic hepatitis C. Liver Int. 2015 Feb;35(2):429-37. doi: 10.1111/liv.12700. Epub 2014 Oct 29.
PMID: 25308921
citation: Helmke S, Colmenero J, Everson GT. Noninvasive assessment of liver function. Curr Opin Gastroenterol. 2015 May;31(3):199-208. doi: 10.1097/MOG.0000000000000167.
PMID: 25714706
citation: Schnabl B, Brenner DA. Interactions between the intestinal microbiome and liver diseases. Gastroenterology. 2014 May;146(6):1513-24. doi: 10.1053/j.gastro.2014.01.020. Epub 2014 Jan 15.
PMID: 24440671
citation: Bonder A, Afdhal N. Utilization of FibroScan in clinical practice. Curr Gastroenterol Rep. 2014 Feb;16(2):372. doi: 10.1007/s11894-014-0372-6.
PMID: 24452634
citation: Chen J, Talwalkar JA, Yin M, Glaser KJ, Sanderson SO, Ehman RL. Early detection of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease by using MR elastography. Radiology. 2011 Jun;259(3):749-56. doi: 10.1148/radiol.11101942. Epub 2011 Apr 1.
PMID: 21460032
citation: Thomas MS, Newman D, Leinhard OD, Kasmai B, Greenwood R, Malcolm PN, Karlsson A, Rosander J, Borga M, Toms AP. Test-retest reliability of automated whole body and compartmental muscle volume measurements on a wide bore 3T MR system. Eur Radiol. 2014 Sep;24(9):2279-91. doi: 10.1007/s00330-014-3226-6. Epub 2014 May 29.
PMID: 24871333
citation: Karlsson A, Rosander J, Romu T, Tallberg J, Gronqvist A, Borga M, Dahlqvist Leinhard O. Automatic and quantitative assessment of regional muscle volume by multi-atlas segmentation using whole-body water-fat MRI. J Magn Reson Imaging. 2015 Jun;41(6):1558-69. doi: 10.1002/jmri.24726. Epub 2014 Aug 11.
PMID: 25111561
citation: West J, Dahlqvist Leinhard O, Romu T, Collins R, Garratt S, Bell JD, Borga M, Thomas L. Feasibility of MR-Based Body Composition Analysis in Large Scale Population Studies. PLoS One. 2016 Sep 23;11(9):e0163332. doi: 10.1371/journal.pone.0163332. eCollection 2016.
PMID: 27662190
citation: Banerjee R, Pavlides M, Tunnicliffe EM, Piechnik SK, Sarania N, Philips R, Collier JD, Booth JC, Schneider JE, Wang LM, Delaney DW, Fleming KA, Robson MD, Barnes E, Neubauer S. Multiparametric magnetic resonance for the non-invasive diagnosis of liver disease. J Hepatol. 2014 Jan;60(1):69-77. doi: 10.1016/j.jhep.2013.09.002. Epub 2013 Sep 12.
PMID: 24036007
citation: Pavlides M, Banerjee R, Sellwood J, Kelly CJ, Robson MD, Booth JC, Collier J, Neubauer S, Barnes E. Multiparametric magnetic resonance imaging predicts clinical outcomes in patients with chronic liver disease. J Hepatol. 2016 Feb;64(2):308-315. doi: 10.1016/j.jhep.2015.10.009. Epub 2015 Nov 10.
PMID: 26471505
responsible party type: Sponsor
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
mesh term: Cholic Acids
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: This trial was limited by the need to close the trial prior to enrolling all participants due to extreme difficulties with recruitment. Based on our power estimates, we needed 25 people in the NASH group, and we were only able to enroll 4. Therefore, our analyses will be limited the basic plans proposed in the protocol and will likely be exploratory and hypothesis generating in nature.
point of contact: 