<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/NCT04440540</url>
  </required_header>
  <id_info>
    <org_study_id>2020.256</org_study_id>
    <nct_id>NCT04440540</nct_id>
  </id_info>
  <brief_title>Alternation of Non-alcoholic Fatty Liver Disease (NAFLD) and Cardiovascular Risks After Liftestyle Modification: A Ultrasound Attenuation Imaging-Based Study</brief_title>
  <official_title>Effectiveness of Lifestyle Modification Program in Reversal of Non-alcoholic Fatty Liver Disease (NAFLD) and Reduction of Cardiovascular Risks in Moderate Obesity: A Ultrasound Attenuation Imaging-Based Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chinese University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chinese University of Hong Kong</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The prevalence of obesity has significantly increased over the last few decades. The&#xD;
      excessive fat accumulation in undesired areas in obese patients may lead to various&#xD;
      complications, such as cardiovascular diseases and Non-alcoholic fatty liver disease (NAFLD)&#xD;
      defined by intrahepatic triglycerides (IHTG) content higher than 5.5%. In Hong Kong, the&#xD;
      incidence rate of NAFLD is as high as approximately 13.5%, while 60.5% of obese subjects&#xD;
      suffer from NAFLD. NAFLD is found to be a well-established risk factor for chronic kidney&#xD;
      disease, type 2 diabetes, and cardiovascular disease. Moreover, obesity is a strong&#xD;
      independent risk factor for development of atherosclerosis. It also plays important role in&#xD;
      pathogenesis of dyslipidaemia, insulin resistance, hypertension. Both NAFLD and&#xD;
      cardiovascular risks can be reversed. Lifestyle modification program(LMP) including diet&#xD;
      control and routine exercise has been widely recommended to patients with mild to moderate&#xD;
      obesity. It is vital to have a non-invasive, non-ionizing, low cost, accessible or widely&#xD;
      available and yet accurate assessment tool to diagnose NAFLD and some cardiovascular risk&#xD;
      parameters and serially monitor changes to assess the efficacy of LMP. Ultrasound meets these&#xD;
      requirements. To the best of our knowledge there has been no prior study similar to this one.&#xD;
      In this study, we aim to assess and validate the diagnostic accuracy of a novel ultrasound&#xD;
      attenuation imaging method for NAFLD, and to evaluate the effectiveness of LMP in reversal of&#xD;
      NAFLD and reduction of cardiovascular risks in moderate obesity.&#xD;
&#xD;
      A total of forty moderate obese patients with NAFLD will be recruited in this study, divided&#xD;
      into lifestyle modification program group(n=20) and usual care group(n=20). All subjects will&#xD;
      undergo dietary assessment based on 3-day diet record and power of food scale. Demographic&#xD;
      data will be recorded, consisted of age, weight, height, waist circumference, BMI, and so on.&#xD;
      Ultrasound attenuation imaging (ATI) will be performed to measure tissue attenuation&#xD;
      coefficient so as to evaluate liver steatosis and liver fibrosis stage. Meanwhile, magnetic&#xD;
      resonance imaging (MRI) will be carried out, which include cardiovascular risks measurement,&#xD;
      liver proton density fat fraction (PDFF), volume quantification of abdominal white adipose&#xD;
      tissue, liver inflammation and fibrosis assessment. Biochemistry tests will be conducted as&#xD;
      supplementary for assessment of NAFLD and cardiovascular risks, comprising liver function&#xD;
      test, lipid, fasting glucose, etc.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 2, 2020</start_date>
  <completion_date type="Anticipated">June 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>intrahepatic triglycerides (IHTG) content</measure>
    <time_frame>1 year</time_frame>
    <description>change of IHTG content in NAFLD assessed by ultrasound</description>
  </primary_outcome>
  <primary_outcome>
    <measure>cardiovascular risks</measure>
    <time_frame>1 year</time_frame>
    <description>cardiovascular risks reflected by Intima-media thicknesses of both carotid arteries</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Non-alcoholic Fatty Liver Disease</condition>
  <arm_group>
    <arm_group_label>lifestyle modification program group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>usual care group (control)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Dietitian led life style modification intervention</intervention_name>
    <description>lifestyle changes supervised by dietitians</description>
    <arm_group_label>lifestyle modification program group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Conventional care (control)</intervention_name>
    <description>receive routine care</description>
    <arm_group_label>usual care group (control)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  With age range of 18-65 years.&#xD;
&#xD;
          -  With diagnosis of NAFLD.&#xD;
&#xD;
          -  BMI =27.5- 32.4kg/m2 for moderate obesity (Asian population)&#xD;
&#xD;
          -  Written consent form obtained.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Other kind of hepatic diseases or under medications known to affect liver fat&#xD;
             accumulation.&#xD;
&#xD;
          -  Excessive alcohol consumption (&gt;20g/d for men and &gt;10g/d for women).&#xD;
&#xD;
          -  Subjects using thyroid hormones, oestrogens, amiodarone, steroids, tamoxifen and beta&#xD;
             blockers (e.g. propranolol).&#xD;
&#xD;
          -  Body weight &gt;250kgs and or/ waist circumference &gt; 150cm.&#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_contact>
    <last_name>Winnie CW Chu, MD</last_name>
    <phone>3505 2299</phone>
    <email>winniechu@cuhk.edu.hk</email>
  </overall_contact>
  <location>
    <facility>
      <name>The Chinese University of Hong Kong, Prince of Wale Hospital</name>
      <address>
        <city>Hong Kong</city>
        <state>Shatin</state>
        <country>Hong Kong</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Winnie CW Chu, MD</last_name>
      <phone>3505 2299</phone>
      <email>winniechu@cuhk.edu.hk</email>
    </contact>
  </location>
  <location_countries>
    <country>Hong Kong</country>
  </location_countries>
  <reference>
    <citation>Carbone S, Canada JM, Billingsley HE, Siddiqui MS, Elagizi A, Lavie CJ. Obesity paradox in cardiovascular disease: where do we stand? Vasc Health Risk Manag. 2019 May 1;15:89-100. doi: 10.2147/VHRM.S168946. eCollection 2019.</citation>
    <PMID>31118651</PMID>
  </reference>
  <reference>
    <citation>Szczepaniak LS, Nurenberg P, Leonard D, Browning JD, Reingold JS, Grundy S, Hobbs HH, Dobbins RL. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab. 2005 Feb;288(2):E462-8. doi: 10.1152/ajpendo.00064.2004. Epub 2004 Aug 31.</citation>
    <PMID>15339742</PMID>
  </reference>
  <reference>
    <citation>Wong VW, Wong GL, Yeung DK, Lau TK, Chan CK, Chim AM, Abrigo JM, Chan RS, Woo J, Tse YK, Chu WC, Chan HL. Incidence of non-alcoholic fatty liver disease in Hong Kong: a population study with paired proton-magnetic resonance spectroscopy. J Hepatol. 2015 Jan;62(1):182-9. doi: 10.1016/j.jhep.2014.08.041. Epub 2014 Sep 6.</citation>
    <PMID>25195550</PMID>
  </reference>
  <reference>
    <citation>Wong VW, Chu WC, Wong GL, Chan RS, Chim AM, Ong A, Yeung DK, Yiu KK, Chu SH, Woo J, Chan FK, Chan HL. Prevalence of non-alcoholic fatty liver disease and advanced fibrosis in Hong Kong Chinese: a population study using proton-magnetic resonance spectroscopy and transient elastography. Gut. 2012 Mar;61(3):409-15. doi: 10.1136/gutjnl-2011-300342. Epub 2011 Aug 16.</citation>
    <PMID>21846782</PMID>
  </reference>
  <reference>
    <citation>Wei JL, Leung JC, Loong TC, Wong GL, Yeung DK, Chan RS, Chan HL, Chim AM, Woo J, Chu WC, Wong VW. Prevalence and Severity of Nonalcoholic Fatty Liver Disease in Non-Obese Patients: A Population Study Using Proton-Magnetic Resonance Spectroscopy. Am J Gastroenterol. 2015 Sep;110(9):1306-14; quiz 1315. doi: 10.1038/ajg.2015.235. Epub 2015 Jul 28.</citation>
    <PMID>26215532</PMID>
  </reference>
  <reference>
    <citation>Mantovani A, Zaza G, Byrne CD, Lonardo A, Zoppini G, Bonora E, Targher G. Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: A systematic review and meta-analysis. Metabolism. 2018 Feb;79:64-76. doi: 10.1016/j.metabol.2017.11.003. Epub 2017 Nov 11.</citation>
    <PMID>29137912</PMID>
  </reference>
  <reference>
    <citation>Mantovani A, Byrne CD, Bonora E, Targher G. Nonalcoholic Fatty Liver Disease and Risk of Incident Type 2 Diabetes: A Meta-analysis. Diabetes Care. 2018 Feb;41(2):372-382. doi: 10.2337/dc17-1902.</citation>
    <PMID>29358469</PMID>
  </reference>
  <reference>
    <citation>Targher G, Byrne CD, Lonardo A, Zoppini G, Barbui C. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis. J Hepatol. 2016 Sep;65(3):589-600. doi: 10.1016/j.jhep.2016.05.013. Epub 2016 May 17.</citation>
    <PMID>27212244</PMID>
  </reference>
  <reference>
    <citation>Liu Y, Zhong GC, Tan HY, Hao FB, Hu JJ. Nonalcoholic fatty liver disease and mortality from all causes, cardiovascular disease, and cancer: a meta-analysis. Sci Rep. 2019 Jul 31;9(1):11124. doi: 10.1038/s41598-019-47687-3.</citation>
    <PMID>31366982</PMID>
  </reference>
  <reference>
    <citation>Akil L, Ahmad HA. Relationships between obesity and cardiovascular diseases in four southern states and Colorado. J Health Care Poor Underserved. 2011;22(4 Suppl):61-72. doi: 10.1353/hpu.2011.0166.</citation>
    <PMID>22102306</PMID>
  </reference>
  <reference>
    <citation>Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N, Hailpern SM, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell C, Roger V, Sorlie P, Steinberger J, Thom T, Wilson M, Hong Y; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2008 Jan 29;117(4):e25-146. doi: 10.1161/CIRCULATIONAHA.107.187998. Epub 2007 Dec 17. No abstract available. Erratum In: Circulation. 2010 Jul 6;122(1):e10. Kissela, Bret [corrected to Kissela, Brett].</citation>
    <PMID>18086926</PMID>
  </reference>
  <reference>
    <citation>Unamuno X, Gomez-Ambrosi J, Rodriguez A, Becerril S, Fruhbeck G, Catalan V. Adipokine dysregulation and adipose tissue inflammation in human obesity. Eur J Clin Invest. 2018 Sep;48(9):e12997. doi: 10.1111/eci.12997. Epub 2018 Aug 3.</citation>
    <PMID>29995306</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>June 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 18, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 19, 2020</study_first_posted>
  <last_update_submitted>August 30, 2023</last_update_submitted>
  <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chinese University of Hong Kong</investigator_affiliation>
    <investigator_full_name>Professor Winnie W.C. Chu</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Ultrasound Attenuation Imaging</keyword>
  <keyword>NAFLD</keyword>
  <keyword>cardiovascular risk</keyword>
  <keyword>lifestyle modification</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
    <mesh_term>Fatty Liver</mesh_term>
    <mesh_term>Non-alcoholic Fatty Liver Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04440540
org study id: 2020.256
nct id: NCT04440540
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The prevalence of obesity has significantly increased over the last few decades. The
      excessive fat accumulation in undesired areas in obese patients may lead to various
      complications, such as cardiovascular diseases and Non-alcoholic fatty liver disease (NAFLD)
      defined by intrahepatic triglycerides (IHTG) content higher than 5.5%. In Hong Kong, the
      incidence rate of NAFLD is as high as approximately 13.5%, while 60.5% of obese subjects
      suffer from NAFLD. NAFLD is found to be a well-established risk factor for chronic kidney
      disease, type 2 diabetes, and cardiovascular disease. Moreover, obesity is a strong
      independent risk factor for development of atherosclerosis. It also plays important role in
      pathogenesis of dyslipidaemia, insulin resistance, hypertension. Both NAFLD and
      cardiovascular risks can be reversed. Lifestyle modification program(LMP) including diet
      control and routine exercise has been widely recommended to patients with mild to moderate
      obesity. It is vital to have a non-invasive, non-ionizing, low cost, accessible or widely
      available and yet accurate assessment tool to diagnose NAFLD and some cardiovascular risk
      parameters and serially monitor changes to assess the efficacy of LMP. Ultrasound meets these
      requirements. To the best of our knowledge there has been no prior study similar to this one.
      In this study, we aim to assess and validate the diagnostic accuracy of a novel ultrasound
      attenuation imaging method for NAFLD, and to evaluate the effectiveness of LMP in reversal of
      NAFLD and reduction of cardiovascular risks in moderate obesity.

      A total of forty moderate obese patients with NAFLD will be recruited in this study, divided
      into lifestyle modification program group(n=20) and usual care group(n=20). All subjects will
      undergo dietary assessment based on 3-day diet record and power of food scale. Demographic
      data will be recorded, consisted of age, weight, height, waist circumference, BMI, and so on.
      Ultrasound attenuation imaging (ATI) will be performed to measure tissue attenuation
      coefficient so as to evaluate liver steatosis and liver fibrosis stage. Meanwhile, magnetic
      resonance imaging (MRI) will be carried out, which include cardiovascular risks measurement,
      liver proton density fat fraction (PDFF), volume quantification of abdominal white adipose
      tissue, liver inflammation and fibrosis assessment. Biochemistry tests will be conducted as
      supplementary for assessment of NAFLD and cardiovascular risks, comprising liver function
      test, lipid, fasting glucose, etc.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: intrahepatic triglycerides (IHTG) content
time frame: 1 year
description: change of IHTG content in NAFLD assessed by ultrasound
measure: cardiovascular risks
time frame: 1 year
description: cardiovascular risks reflected by Intima-media thicknesses of both carotid arteries
arm group label: lifestyle modification program group
arm group type: Experimental
arm group label: usual care group (control)
arm group type: Experimental
intervention type: Behavioral
intervention name: Dietitian led life style modification intervention
description: lifestyle changes supervised by dietitians
arm group label: lifestyle modification program group
intervention type: Behavioral
intervention name: Conventional care (control)
description: receive routine care
arm group label: usual care group (control)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Winnie CW Chu, MD
phone: 3505 2299
email: winniechu@cuhk.edu.hk
facility: 
status: Recruiting
contact: 
country: Hong Kong
citation: Carbone S, Canada JM, Billingsley HE, Siddiqui MS, Elagizi A, Lavie CJ. Obesity paradox in cardiovascular disease: where do we stand? Vasc Health Risk Manag. 2019 May 1;15:89-100. doi: 10.2147/VHRM.S168946. eCollection 2019.
PMID: 31118651
citation: Szczepaniak LS, Nurenberg P, Leonard D, Browning JD, Reingold JS, Grundy S, Hobbs HH, Dobbins RL. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab. 2005 Feb;288(2):E462-8. doi: 10.1152/ajpendo.00064.2004. Epub 2004 Aug 31.
PMID: 15339742
citation: Wong VW, Wong GL, Yeung DK, Lau TK, Chan CK, Chim AM, Abrigo JM, Chan RS, Woo J, Tse YK, Chu WC, Chan HL. Incidence of non-alcoholic fatty liver disease in Hong Kong: a population study with paired proton-magnetic resonance spectroscopy. J Hepatol. 2015 Jan;62(1):182-9. doi: 10.1016/j.jhep.2014.08.041. Epub 2014 Sep 6.
PMID: 25195550
citation: Wong VW, Chu WC, Wong GL, Chan RS, Chim AM, Ong A, Yeung DK, Yiu KK, Chu SH, Woo J, Chan FK, Chan HL. Prevalence of non-alcoholic fatty liver disease and advanced fibrosis in Hong Kong Chinese: a population study using proton-magnetic resonance spectroscopy and transient elastography. Gut. 2012 Mar;61(3):409-15. doi: 10.1136/gutjnl-2011-300342. Epub 2011 Aug 16.
PMID: 21846782
citation: Wei JL, Leung JC, Loong TC, Wong GL, Yeung DK, Chan RS, Chan HL, Chim AM, Woo J, Chu WC, Wong VW. Prevalence and Severity of Nonalcoholic Fatty Liver Disease in Non-Obese Patients: A Population Study Using Proton-Magnetic Resonance Spectroscopy. Am J Gastroenterol. 2015 Sep;110(9):1306-14; quiz 1315. doi: 10.1038/ajg.2015.235. Epub 2015 Jul 28.
PMID: 26215532
citation: Mantovani A, Zaza G, Byrne CD, Lonardo A, Zoppini G, Bonora E, Targher G. Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: A systematic review and meta-analysis. Metabolism. 2018 Feb;79:64-76. doi: 10.1016/j.metabol.2017.11.003. Epub 2017 Nov 11.
PMID: 29137912
citation: Mantovani A, Byrne CD, Bonora E, Targher G. Nonalcoholic Fatty Liver Disease and Risk of Incident Type 2 Diabetes: A Meta-analysis. Diabetes Care. 2018 Feb;41(2):372-382. doi: 10.2337/dc17-1902.
PMID: 29358469
citation: Targher G, Byrne CD, Lonardo A, Zoppini G, Barbui C. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis. J Hepatol. 2016 Sep;65(3):589-600. doi: 10.1016/j.jhep.2016.05.013. Epub 2016 May 17.
PMID: 27212244
citation: Liu Y, Zhong GC, Tan HY, Hao FB, Hu JJ. Nonalcoholic fatty liver disease and mortality from all causes, cardiovascular disease, and cancer: a meta-analysis. Sci Rep. 2019 Jul 31;9(1):11124. doi: 10.1038/s41598-019-47687-3.
PMID: 31366982
citation: Akil L, Ahmad HA. Relationships between obesity and cardiovascular diseases in four southern states and Colorado. J Health Care Poor Underserved. 2011;22(4 Suppl):61-72. doi: 10.1353/hpu.2011.0166.
PMID: 22102306
citation: Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N, Hailpern SM, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell C, Roger V, Sorlie P, Steinberger J, Thom T, Wilson M, Hong Y; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2008 Jan 29;117(4):e25-146. doi: 10.1161/CIRCULATIONAHA.107.187998. Epub 2007 Dec 17. No abstract available. Erratum In: Circulation. 2010 Jul 6;122(1):e10. Kissela, Bret [corrected to Kissela, Brett].
PMID: 18086926
citation: Unamuno X, Gomez-Ambrosi J, Rodriguez A, Becerril S, Fruhbeck G, Catalan V. Adipokine dysregulation and adipose tissue inflammation in human obesity. Eur J Clin Invest. 2018 Sep;48(9):e12997. doi: 10.1111/eci.12997. Epub 2018 Aug 3.
PMID: 29995306
responsible party type: Principal Investigator
investigator affiliation: Chinese University of Hong Kong
investigator full name: Professor Winnie W.C. Chu
investigator title: Professor
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
sharing ipd: No