<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/NCT04411862</url>
  </required_header>
  <id_info>
    <org_study_id>NAFLD</org_study_id>
    <nct_id>NCT04411862</nct_id>
  </id_info>
  <brief_title>Efficacy of Phosphatidylcholine in NAFLD</brief_title>
  <official_title>Efficacy of Phosphatidylcholine in Addition to Behavior Therapy by Clinical Pharmacist in the Management of Non Alcoholic Fatty Liver (NAFLD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nehal Abou Seada</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ain Shams University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates efficacy of Phosphatidylcholine in addition to life style modification&#xD;
      and patient health education by clinical Pharmacist in the Management of Non Alcoholic Fatty&#xD;
      Liver NAFLD. All participants with NAFLD will receive life style intervention and half of&#xD;
      them will receive additionally Phosphatidylcholine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      As a result of increasing rates of obesity Non Alcoholic Fatty Liver (NAFLD) is the most&#xD;
      common liver disorder affecting 17-46% of adults and parallels the prevalence of Metabolic&#xD;
      Syndrome (MetS) and its components which also increases the risk of more advanced disease&#xD;
      both in adults and in children.&#xD;
&#xD;
      Its pathogenesis is complex and multifactorial, mainly involving genetic, environmental and&#xD;
      metabolic factors. New concepts are constantly appearing in the literature, promising new&#xD;
      diagnostic and therapeutic tools. Further studies are needed to better characterize not only&#xD;
      NAFLD development but overall NAFLD progression, in order to better identify NAFLD patients&#xD;
      at higher risk of metabolic, cardiovascular and neoplastic complications. Pharmacological&#xD;
      treatments aimed primarily at improving liver disease should generally be limited to those&#xD;
      with biopsy-proven Nonalcoholic steatohepatitis (NASH) and liver ﬁbrosis. Not much&#xD;
      therapeutic options for NAFLD are accepted until today besides correction of obesity with&#xD;
      hypocaloric diets and physical exercise and controlling hyperglycemia with diet, insulin, or&#xD;
      oral hypoglycemic agents. Weight loss generally reduces hepatic steatosis.Essential&#xD;
      phospholipid (EPL) as a nutritional supplement is one of the drugs under discussion with&#xD;
      significant positive effects as antioxidative, antifibrotic effects and high biocompatibility&#xD;
      on NAFLD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2, 2016</start_date>
  <completion_date type="Actual">July 1, 2019</completion_date>
  <primary_completion_date type="Actual">January 3, 2019</primary_completion_date>
  <phase>Phase 3</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>Shams University Hospitals and Ain Shams Specialized Hospital outpatient Gastroenterology Clinics.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>change from baseline Body Mass Index (BMI) at 3 and 6 month</measure>
    <time_frame>baseline, at 3 and 6 month</time_frame>
    <description>person's weight in kilograms divided by the square of the person's height in metres (kg/m2).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change from baseline liver stiffness at 3 and 6 month</measure>
    <time_frame>baseline , at 3 and 6 month</time_frame>
    <description>Liver Stiffness and fibrosis score measured by Transient elastography (Fibroscan) F0 = no fibrosis F1 = portal fibrosis without septa F2 = portal fibrosis with few septa F3 = numerous septa without cirrhosis F4 = cirrhosis</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change from baseline Lipid Profile</measure>
    <time_frame>baseline , at 3 and 6 month</time_frame>
    <description>Total cholesterol ,Triglyceride ,Low Density Lipoprotein ,High Density Lipoprotein</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change from baseline Oxidative stress markers</measure>
    <time_frame>baseline , at 3 and 6 month</time_frame>
    <description>malonaldehyde (MDA) as an index of lipid peroxidation by colorimetric assay</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change from baseline NAFLD score at 3 and 6 month</measure>
    <time_frame>baseline , at 3 and 6 month</time_frame>
    <description>NAFLD Fibrosis Score is based on six readily available variables (age, BMI, hyperglycemia, albumin, platelet count, AST/ALT ratio) and it is calculated using published formula (http: //naflds- core.com) . A low cutpoint (score &lt; -1.455) signified the absence of advanced fibrosis, whereas a high cutpoint (score&gt; 0.676) identified advanced fibrosis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change from baseline homeostasis model assessment Insulin resistance HOMA IR scores at 3 and 6 month</measure>
    <time_frame>baseline , at 3 and 6 month</time_frame>
    <description>HOMA IR scores &lt;3 normal HOMA IR scores &gt;5 severe insulin resistance 3 to 5 moderate insulin resistance</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>change from baseline Complete Blood Picture at 3 and 6 month</measure>
    <time_frame>baseline , at 3 and 6 month</time_frame>
    <description>platelet count</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Non-Alcoholic Fatty Liver Disease</condition>
  <arm_group>
    <arm_group_label>Intervention Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>50 Participants with NAFLD that receive lifestyle modification by Clinical Pharmacist plus Phosphatidylcholine two soft capsules 3 times daily(2.1 g per day) for 6 month</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>50 Participants with NAFLD that receive only lifestyle modification by Clinical Pharmacist</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Phosphatidyl Choline</intervention_name>
    <description>2.1 g Phosphatidylcholine daily in addition to lifestyle modification</description>
    <arm_group_label>Intervention Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Lifestyle modification</intervention_name>
    <description>Lifestyle modification and health education by Clinical Pharmacist</description>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_label>Intervention Group</arm_group_label>
    <other_name>Behavior therapy</other_name>
    <other_name>Health education</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Patients were included in the study when the following criteria to were fulfilled :&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  fatty liver upon Ultrasonography (US) /Computed Tomography (CT) /Magnetic Resonance&#xD;
             Imaging (MRI) with either incidental increased Alanine Aminotransferase (ALT)&#xD;
&#xD;
          -  the presence of risk factors related to NAFLD + increased ALT&#xD;
&#xD;
          -  symptomatic liver disease +/- hepatomegaly, +/- increased ALT&#xD;
&#xD;
          -  homeostasis model assessment-insulin resistance HOMA IR score &gt; 3&#xD;
&#xD;
          -  presence of liver steatosis or stiffness measured by transient elastography&#xD;
&#xD;
          -  eligible patients had at least one of the following metabolic comorbidities:&#xD;
             hypertension, Type 2 Diabetes Mellitus, overweight/obesity (BMI&gt;27 kg/m2) serum&#xD;
             cholesterol of &gt; 200 mg/d&#xD;
&#xD;
        Patients were excluded from the study if showing evidence :&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  if showing evidence of alcoholic or chronic liver disease&#xD;
&#xD;
          -  Hepatocellular Carcinoma, autoimmune hepatitis&#xD;
&#xD;
          -  end stage liver disease&#xD;
&#xD;
          -  treatment with other hepatoprotectants&#xD;
&#xD;
          -  other concomitant EPL within 30 days of study initiation&#xD;
&#xD;
          -  pregnancy or lactation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <reference>
    <citation>National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002 Dec 17;106(25):3143-421. No abstract available.</citation>
    <PMID>12485966</PMID>
  </reference>
  <reference>
    <citation>European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016 Jun;64(6):1388-402. doi: 10.1016/j.jhep.2015.11.004. Epub 2016 Apr 7. No abstract available.</citation>
    <PMID>27062661</PMID>
  </reference>
  <reference>
    <citation>Chalasani N; Writing Group for American Association for Study of Liver Diseases; American College of Gastroenterology; American Gastroenterology Association practice guideline on Diagnosis and Management of Nonalcoholic Fatty Liver Disease. Reply: To PMID 22488764. Hepatology. 2013 Feb;57(2):853-4. doi: 10.1002/hep.26199. Epub 2013 Jan 7. No abstract available.</citation>
    <PMID>23297154</PMID>
  </reference>
  <reference>
    <citation>Ahmed MH, Noor SK, Bushara SO, Husain NE, Elmadhoun WM, Ginawi IA, Osman MM, Mahmoud AO, Almobarak AO. Non-Alcoholic Fatty Liver Disease in Africa and Middle East: An Attempt to Predict the Present and Future Implications on the Healthcare System. Gastroenterology Res. 2017 Oct;10(5):271-279. doi: 10.14740/gr913w. Epub 2017 Oct 26.</citation>
    <PMID>29118867</PMID>
  </reference>
  <results_reference>
    <citation>Gundermann KJ, Gundermann S, Drozdzik M, Mohan Prasad VG. Essential phospholipids in fatty liver: a scientific update. Clin Exp Gastroenterol. 2016 May 5;9:105-17. doi: 10.2147/CEG.S96362. eCollection 2016.</citation>
    <PMID>27217791</PMID>
  </results_reference>
  <results_reference>
    <citation>Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM, Sanyal AJ. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018 Jan;67(1):328-357. doi: 10.1002/hep.29367. Epub 2017 Sep 29. No abstract available.</citation>
    <PMID>28714183</PMID>
  </results_reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>May 10, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>June 1, 2020</last_update_submitted>
  <last_update_submitted_qc>June 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Ain Shams University</investigator_affiliation>
    <investigator_full_name>Nehal Abou Seada</investigator_full_name>
    <investigator_title>Principal Investigator</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Choline</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04411862
org study id: NAFLD
nct id: NCT04411862
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study evaluates efficacy of Phosphatidylcholine in addition to life style modification
      and patient health education by clinical Pharmacist in the Management of Non Alcoholic Fatty
      Liver NAFLD. All participants with NAFLD will receive life style intervention and half of
      them will receive additionally Phosphatidylcholine.
As a result of increasing rates of obesity Non Alcoholic Fatty Liver (NAFLD) is the most
      common liver disorder affecting 17-46% of adults and parallels the prevalence of Metabolic
      Syndrome (MetS) and its components which also increases the risk of more advanced disease
      both in adults and in children.

      Its pathogenesis is complex and multifactorial, mainly involving genetic, environmental and
      metabolic factors. New concepts are constantly appearing in the literature, promising new
      diagnostic and therapeutic tools. Further studies are needed to better characterize not only
      NAFLD development but overall NAFLD progression, in order to better identify NAFLD patients
      at higher risk of metabolic, cardiovascular and neoplastic complications. Pharmacological
      treatments aimed primarily at improving liver disease should generally be limited to those
      with biopsy-proven Nonalcoholic steatohepatitis (NASH) and liver ﬁbrosis. Not much
      therapeutic options for NAFLD are accepted until today besides correction of obesity with
      hypocaloric diets and physical exercise and controlling hyperglycemia with diet, insulin, or
      oral hypoglycemic agents. Weight loss generally reduces hepatic steatosis.Essential
      phospholipid (EPL) as a nutritional supplement is one of the drugs under discussion with
      significant positive effects as antioxidative, antifibrotic effects and high biocompatibility
      on NAFLD.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Shams University Hospitals and Ain Shams Specialized Hospital outpatient Gastroenterology Clinics.
primary purpose: Treatment
masking: None (Open Label)
measure: change from baseline Body Mass Index (BMI) at 3 and 6 month
time frame: baseline, at 3 and 6 month
description: person's weight in kilograms divided by the square of the person's height in metres (kg/m2).
measure: change from baseline liver stiffness at 3 and 6 month
time frame: baseline , at 3 and 6 month
description: Liver Stiffness and fibrosis score measured by Transient elastography (Fibroscan) F0 = no fibrosis F1 = portal fibrosis without septa F2 = portal fibrosis with few septa F3 = numerous septa without cirrhosis F4 = cirrhosis
measure: change from baseline Lipid Profile
time frame: baseline , at 3 and 6 month
description: Total cholesterol ,Triglyceride ,Low Density Lipoprotein ,High Density Lipoprotein
measure: change from baseline Oxidative stress markers
time frame: baseline , at 3 and 6 month
description: malonaldehyde (MDA) as an index of lipid peroxidation by colorimetric assay
measure: change from baseline NAFLD score at 3 and 6 month
time frame: baseline , at 3 and 6 month
description: NAFLD Fibrosis Score is based on six readily available variables (age, BMI, hyperglycemia, albumin, platelet count, AST/ALT ratio) and it is calculated using published formula (http: //naflds- core.com) . A low cutpoint (score < -1.455) signified the absence of advanced fibrosis, whereas a high cutpoint (score> 0.676) identified advanced fibrosis.
measure: change from baseline homeostasis model assessment Insulin resistance HOMA IR scores at 3 and 6 month
time frame: baseline , at 3 and 6 month
description: HOMA IR scores <3 normal HOMA IR scores >5 severe insulin resistance 3 to 5 moderate insulin resistance
measure: change from baseline Complete Blood Picture at 3 and 6 month
time frame: baseline , at 3 and 6 month
description: platelet count
arm group label: Intervention Group
arm group type: Experimental
description: 50 Participants with NAFLD that receive lifestyle modification by Clinical Pharmacist plus Phosphatidylcholine two soft capsules 3 times daily(2.1 g per day) for 6 month
arm group label: Control Group
arm group type: Active Comparator
description: 50 Participants with NAFLD that receive only lifestyle modification by Clinical Pharmacist
intervention type: Dietary Supplement
intervention name: Phosphatidyl Choline
description: 2.1 g Phosphatidylcholine daily in addition to lifestyle modification
arm group label: Intervention Group
intervention type: Behavioral
intervention name: Lifestyle modification
description: Lifestyle modification and health education by Clinical Pharmacist
arm group label: Control Group
arm group label: Intervention Group
other name: Behavior therapy
other name: Health education
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
citation: National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002 Dec 17;106(25):3143-421. No abstract available.
PMID: 12485966
citation: European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016 Jun;64(6):1388-402. doi: 10.1016/j.jhep.2015.11.004. Epub 2016 Apr 7. No abstract available.
PMID: 27062661
citation: Chalasani N; Writing Group for American Association for Study of Liver Diseases; American College of Gastroenterology; American Gastroenterology Association practice guideline on Diagnosis and Management of Nonalcoholic Fatty Liver Disease. Reply: To PMID 22488764. Hepatology. 2013 Feb;57(2):853-4. doi: 10.1002/hep.26199. Epub 2013 Jan 7. No abstract available.
PMID: 23297154
citation: Ahmed MH, Noor SK, Bushara SO, Husain NE, Elmadhoun WM, Ginawi IA, Osman MM, Mahmoud AO, Almobarak AO. Non-Alcoholic Fatty Liver Disease in Africa and Middle East: An Attempt to Predict the Present and Future Implications on the Healthcare System. Gastroenterology Res. 2017 Oct;10(5):271-279. doi: 10.14740/gr913w. Epub 2017 Oct 26.
PMID: 29118867
citation: Gundermann KJ, Gundermann S, Drozdzik M, Mohan Prasad VG. Essential phospholipids in fatty liver: a scientific update. Clin Exp Gastroenterol. 2016 May 5;9:105-17. doi: 10.2147/CEG.S96362. eCollection 2016.
PMID: 27217791
citation: Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM, Sanyal AJ. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018 Jan;67(1):328-357. doi: 10.1002/hep.29367. Epub 2017 Sep 29. No abstract available.
PMID: 28714183
responsible party type: Sponsor-Investigator
investigator affiliation: Ain Shams University
investigator full name: Nehal Abou Seada
investigator title: Principal Investigator
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
mesh term: Choline