<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/NCT04475276</url>
  </required_header>
  <id_info>
    <org_study_id>T/IM-F/19-20/16</org_study_id>
    <nct_id>NCT04475276</nct_id>
  </id_info>
  <brief_title>Effect of Alpha Lipoic Acid on Non-alcoholic Fatty Liver Diseases</brief_title>
  <official_title>Effect of Alpha Lipoic Acid on Non-alcoholic Fatty Liver Diseases: A Randomized Placebo-controlled Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>All India Institute of Medical Sciences, Bhubaneswar</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>All India Institute of Medical Sciences, Bhubaneswar</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In developed counties Non-alcoholic fatty liver disease (NAFLD) becomes the most common cause&#xD;
      of chronic liver disease , but its prevalence in developing countries like India is also&#xD;
      increasing (10 -20%).Till date, there is no US-FDA approved therapy for NAFLD but drugs like&#xD;
      metformin, pioglitazone, sitagliptin, vildagliptin Vitamin E, silymarin, statins and&#xD;
      ezetimibe have been studied along with life style modification. Life style modifications is&#xD;
      the current modality of treatment of NAFLD. All the above-mentioned drugs have some&#xD;
      beneficial effects with limited use due to its adverse effects in patients of NAFLD and the&#xD;
      study results are non-conclusive. In this scenario, a safe hepatoprotective drug to be&#xD;
      evaluated in NAFLD.Alpha-lipoic acid (ALA) or 6,8-thioctic acid, is an endogenous molecule&#xD;
      which functions as an important co-factor for various enzyme complexes in mitochondria and&#xD;
      plays an important role in energy metabolism. ALA is a nutraceutical agent which also has&#xD;
      hepatoprotective and anti-inﬂammatory effects.ALA is a nutraceutic having anti-inflammatory&#xD;
      and antioxidant effects and also increasing insulin sensitivity with lesser adverse effects.&#xD;
      The relative scarcity of a promising therapy and non-conclusiveness of the previous studies&#xD;
      open up an arena of further research using a nutraceutic in non-diabetic NAFLD. So, the&#xD;
      present study is designed to evaluate safety and efficacy of ALA in non-diabetic NAFLD&#xD;
      patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In developed counties Non-alcoholic fatty liver disease (NAFLD) becomes the most common cause&#xD;
      of chronic liver disease , but its prevalence in developing countries like India is also&#xD;
      increasing (10 -20%). Most of the patients are diagnosed clinically and by increased serum&#xD;
      transaminase and fatty changes in liver on abdominal ultrasound. Till date, there is no&#xD;
      US-FDA approved therapy for NAFLD but drugs like metformin, pioglitazone, sitagliptin,&#xD;
      vildagliptin Vitamin E, silymarin, statins and ezetimibe have been studied along with life&#xD;
      style modification. Life style modifications is the current modality of treatment of NAFLD.&#xD;
      All the above-mentioned drugs have some beneficial effects with limited use due to its&#xD;
      adverse effects in patients of NAFLD and the study results are non-conclusive. In this&#xD;
      scenario, a safe hepatoprotective drug to be evaluated in NAFLD.&#xD;
&#xD;
      Alpha-lipoic acid (ALA) or 6,8-thioctic acid, is an endogenous molecule which functions as an&#xD;
      important co-factor for various enzyme complexes in mitochondria and plays an important role&#xD;
      in energy metabolism. ALA is a nutraceutical agent which also has hepatoprotective and&#xD;
      anti-inﬂammatory effects. Previous animal studies proved the hepatoprotective effect of alpha&#xD;
      lipoic acid on various animal models. Inflammatory liver injury involves the production of&#xD;
      inflammatory mediators like nitric oxide and TNF-alpha. Alpha -Lipoic acid significantly&#xD;
      inhibits production of nitric oxide and TNF-alpha. The reduced production of nitric oxide and&#xD;
      TNF-alpha in Kupffer cells may be involved in the hepatoprotective action conveyed by&#xD;
      alpha-lipoic acid.It has been proved that ALA has potent anti - inflammatory and anti-&#xD;
      oxidant properties.&#xD;
&#xD;
      Insulin resistance is associated with impaired hepatic cell damage, intrahepatic cholestasis,&#xD;
      atherogenic dyslipidaemia and fibrosis in patients of NAFLD. Daily treatment with ALA for 28&#xD;
      days significantly improved insulin sensitivity performance in mice by decreasing insulin&#xD;
      resistance, IL-6 levels, acetylcholinesterase enzyme activity and oxidative stress in liver.&#xD;
      Various studies have shown that the ALA can efficiently improve insulin sensitivity and&#xD;
      reverse the insulin resistance. Cytokeratin 18 (CK 18) is released into circulation as a&#xD;
      consequence of oxidative stress, hepatocyte apoptosis or inflammation in response to lipid&#xD;
      metabolism in NAFLD. CK - 18 level is higher in insulin resistance.&#xD;
&#xD;
      ALA is a nutraceutic having anti-inflammatory and antioxidant effects and also increasing&#xD;
      insulin sensitivity with lesser adverse effects. The relative scarcity of a promising therapy&#xD;
      and non-conclusiveness of the previous studies open up an arena of further research using a&#xD;
      nutraceutic in non-diabetic NAFLD. So, the present study is designed to evaluate safety and&#xD;
      efficacy of ALA in non-diabetic NAFLD patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 23, 2021</start_date>
  <completion_date type="Anticipated">November 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">October 31, 2023</primary_completion_date>
  <phase>Phase 4</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>A randomized, parallel design placebo-controlled clinical trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
    <masking_description>The patients and the physician will be blinded</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Abdominal ultrasound</measure>
    <time_frame>12 weeks</time_frame>
    <description>the change in fatty liver grading in NAFLD assessed by abdominal ultrasound</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Insulin resistance</measure>
    <time_frame>12 weeks</time_frame>
    <description>changes in insulin resistance by using HOMA IR after therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lipid profile</measure>
    <time_frame>12 weeks</time_frame>
    <description>Change in lipid profile (Total Cholesterol, HDL, LDL,Triglycerides, VLDL) after therapy&#xD;
•</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levels of glutathione reductase</measure>
    <time_frame>12 weeks</time_frame>
    <description>changes in levels of glutathione reductase after therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>levels of Cytokeratin-18</measure>
    <time_frame>12 weeks</time_frame>
    <description>changes in levels of Cytokeratin-18 after therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levels of Alanine transaminase (ALT)</measure>
    <time_frame>12 weeks</time_frame>
    <description>changes in Alanine transaminase units per litre after therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levels of Aspartate transaminase (AST)</measure>
    <time_frame>12 weeks</time_frame>
    <description>changes in Aspartate transaminase (AST)units per litre after therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levels of Alkaline phosphatase (ALP)</measure>
    <time_frame>12 weeks</time_frame>
    <description>changes in Alkaline phosphatase (ALP) in IU after therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levels of Albumin and total protein.</measure>
    <time_frame>12 weeks</time_frame>
    <description>changes in Albumin and total protein in gm/L after therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levels of Bilirubin</measure>
    <time_frame>12 weeks</time_frame>
    <description>changes in Bilirubin in μmol/L after therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levels of total protein</measure>
    <time_frame>12 weeks</time_frame>
    <description>changes in total protein in gm/L after therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levels of Gamma-glutamyltransferase (GGT).</measure>
    <time_frame>12 weeks</time_frame>
    <description>changes in Gamma-glutamyltransferase (GGT) units per liter after therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levels of L-lactate dehydrogenase (LDH).</measure>
    <time_frame>12 weeks</time_frame>
    <description>changes in L-lactate dehydrogenase (LDH) units per liter after therapy</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Non-Alcoholic Fatty Liver Disease</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Life style modification with the placebo will be given for 12 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Alphalipoic acid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Life style modification with Alpha lipoic acid in a dose of 600mg twice daily will be prescribed orally for 12 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Lifestyle modification with placebo for 12 weeks</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alphalipoic acid</intervention_name>
    <description>Lifestyle modification with Alphalipoic acid for 12 weeks</description>
    <arm_group_label>Alphalipoic acid</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All patients diagnosed to have fatty liver grading 1, 2, 3 on abdominal ultrasound,&#xD;
             mild to moderate elevation (&lt;5 times elevated upper limit) of serum aminotransferase&#xD;
             level.&#xD;
&#xD;
          -  Patients aged 18-65 years of either sex.&#xD;
&#xD;
          -  Treatment naïve patients or patients who had not taken any treatment for at least 4&#xD;
             weeks before inclusion&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of diabetes mellitus, decompensated liver disease, ascites, oesophageal&#xD;
             varices.&#xD;
&#xD;
          -  Drug abusers and Alcoholics.&#xD;
&#xD;
          -  HBs Ag positive, Anti HCV and HIV, hereditary defects of iron, copper and alpha- 1&#xD;
             antitrypsin deficient patients.&#xD;
&#xD;
          -  Hypothyroidism, obstructive sleep apnoea, total parenteral nutrition, short bowel&#xD;
             syndrome, pancreatoduodenal resection which are secondary causes of NAFLD.&#xD;
&#xD;
          -  Drug users such as corticosteroids, antiviral (nucleoside analogue), tetracycline,&#xD;
             methotrexate, tamoxifen and amiodarone.&#xD;
&#xD;
          -  Patients who are taking any antihyperlipidemic and anti-diabetic agents.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rituparna Maiti, MD</last_name>
    <role>Study Director</role>
    <affiliation>Additional Professor</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Monalisa Jena, MD</last_name>
    <phone>9438884193</phone>
    <email>drmonalisajena@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rituparna Maiti, MD</last_name>
    <phone>9438884191</phone>
    <email>pharm_rituparna@aiimsbhubaneswar.edu.in</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>AIIMS</name>
      <address>
        <city>Bhubaneswar</city>
        <state>Odisha</state>
        <zip>751019</zip>
        <country>India</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Monalisa Jena, MD</last_name>
      <phone>9438884193</phone>
      <email>drmonalisajena@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Rituparna Maiti, MD</last_name>
      <phone>9438884191</phone>
      <email>pharm_rituparna@aiimsbhubaneswar.edu.in</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <results_reference>
    <citation>Hussain M, Majeed Babar MZ, Hussain MS, Akhtar L. Vildagliptin ameliorates biochemical, metabolic and fatty changes associated with non alcoholic fatty liver disease. Pak J Med Sci. 2016 Nov-Dec;32(6):1396-1401. doi: 10.12669/pjms.326.11133.</citation>
    <PMID>28083033</PMID>
  </results_reference>
  <results_reference>
    <citation>Patel SS, Siddiqui MS. Current and Emerging Therapies for Non-alcoholic Fatty Liver Disease. Drugs. 2019 Jan;79(1):75-84. doi: 10.1007/s40265-018-1040-1.</citation>
    <PMID>30588564</PMID>
  </results_reference>
  <results_reference>
    <citation>Cavestro C, Bedogni G, Molinari F, Mandrino S, Rota E, Frigeri MC. Alpha-Lipoic Acid Shows Promise to Improve Migraine in Patients with Insulin Resistance: A 6-Month Exploratory Study. J Med Food. 2018 Mar;21(3):269-273. doi: 10.1089/jmf.2017.0068. Epub 2017 Oct 4.</citation>
    <PMID>28976801</PMID>
  </results_reference>
  <results_reference>
    <citation>Fayez AM, Zakaria S, Moustafa D. Alpha lipoic acid exerts antioxidant effect via Nrf2/HO-1 pathway activation and suppresses hepatic stellate cells activation induced by methotrexate in rats. Biomed Pharmacother. 2018 Sep;105:428-433. doi: 10.1016/j.biopha.2018.05.145. Epub 2018 Jun 5.</citation>
    <PMID>29879626</PMID>
  </results_reference>
  <results_reference>
    <citation>Sadek KM, Saleh EA, Nasr SM. Molecular hepatoprotective effects of lipoic acid against carbon tetrachloride-induced liver fibrosis in rats: Hepatoprotection at molecular level. Hum Exp Toxicol. 2018 Feb;37(2):142-154. doi: 10.1177/0960327117693066. Epub 2017 Feb 21.</citation>
    <PMID>29233029</PMID>
  </results_reference>
  <results_reference>
    <citation>Singh SP, Misra B, Kar SK, Panigrahi MK, Misra D, Bhuyan P, Pattnaik K, Meher C, Agrawal O, Rout N, Swain M. Nonalcoholic fatty liver disease (NAFLD) without insulin resistance: Is it different? Clin Res Hepatol Gastroenterol. 2015 Sep;39(4):482-8. doi: 10.1016/j.clinre.2014.08.014. Epub 2014 Dec 17.</citation>
    <PMID>25543522</PMID>
  </results_reference>
  <results_reference>
    <citation>Ahuja S, Uniyal A, Akhtar A, Sah SP. Alpha lipoic acid and metformin alleviates experimentally induced insulin resistance and cognitive deficit by modulation of TLR2 signalling. Pharmacol Rep. 2019 Aug;71(4):614-623. doi: 10.1016/j.pharep.2019.02.016. Epub 2019 Feb 23.</citation>
    <PMID>31176103</PMID>
  </results_reference>
  <results_reference>
    <citation>He L, Deng L, Zhang Q, Guo J, Zhou J, Song W, Yuan F. Diagnostic Value of CK-18, FGF-21, and Related Biomarker Panel in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Biomed Res Int. 2017;2017:9729107. doi: 10.1155/2017/9729107. Epub 2017 Feb 23.</citation>
    <PMID>28326329</PMID>
  </results_reference>
  <results_reference>
    <citation>Tomic D, Kemp WW, Roberts SK. Nonalcoholic fatty liver disease: current concepts, epidemiology and management strategies. Eur J Gastroenterol Hepatol. 2018 Oct;30(10):1103-1115. doi: 10.1097/MEG.0000000000001235.</citation>
    <PMID>30113367</PMID>
  </results_reference>
  <results_reference>
    <citation>Wu G, Li H, Fang Q, Zhang J, Zhang M, Zhang L, Wu L, Hou X, Lu J, Bao Y, Jia W. Complementary Role of Fibroblast Growth Factor 21 and Cytokeratin 18 in Monitoring the Different Stages of Nonalcoholic Fatty Liver Disease. Sci Rep. 2017 Jul 11;7(1):5095. doi: 10.1038/s41598-017-05257-5.</citation>
    <PMID>28698650</PMID>
  </results_reference>
  <results_reference>
    <citation>Schurks M, Glynn RJ, Rist PM, Tzourio C, Kurth T. Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials. BMJ. 2010 Nov 4;341:c5702. doi: 10.1136/bmj.c5702.</citation>
    <PMID>21051774</PMID>
  </results_reference>
  <results_reference>
    <citation>Dulai PS, Singh S, Patel J, Soni M, Prokop LJ, Younossi Z, Sebastiani G, Ekstedt M, Hagstrom H, Nasr P, Stal P, Wong VW, Kechagias S, Hultcrantz R, Loomba R. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis. Hepatology. 2017 May;65(5):1557-1565. doi: 10.1002/hep.29085. Epub 2017 Mar 31.</citation>
    <PMID>28130788</PMID>
  </results_reference>
  <results_reference>
    <citation>Khalaf AA, Zaki AR, Galal MK, Ogaly HA, Ibrahim MA, Hassan A. The potential protective effect of alpha-lipoic acid against nanocopper particle-induced hepatotoxicity in male rats. Hum Exp Toxicol. 2017 Sep;36(9):881-891. doi: 10.1177/0960327116674526. Epub 2016 Nov 12.</citation>
    <PMID>27827802</PMID>
  </results_reference>
  <results_reference>
    <citation>Abdel-Daim MM, Taha R, Ghazy EW, El-Sayed YS. Synergistic ameliorative effects of sesame oil and alpha-lipoic acid against subacute diazinon toxicity in rats: hematological, biochemical, and antioxidant studies. Can J Physiol Pharmacol. 2016 Jan;94(1):81-8. doi: 10.1139/cjpp-2015-0131. Epub 2015 Jul 19.</citation>
    <PMID>26550680</PMID>
  </results_reference>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>July 10, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 17, 2020</study_first_posted>
  <last_update_submitted>July 24, 2023</last_update_submitted>
  <last_update_submitted_qc>July 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>All India Institute of Medical Sciences, Bhubaneswar</investigator_affiliation>
    <investigator_full_name>Dr. Monalisa Jena, M.D.</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Non alcoholic fatty liver</keyword>
  <keyword>Alphalipoic acid</keyword>
  <keyword>Nutraceutic</keyword>
  <keyword>Insulin resistance</keyword>
  <keyword>Cytokeratin 18</keyword>
  <keyword>Life style modification</keyword>
  <keyword>Vitamin E</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thioctic Acid</mesh_term>
  </intervention_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/NCT04475276
org study id: T/IM-F/19-20/16
nct id: NCT04475276
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In developed counties Non-alcoholic fatty liver disease (NAFLD) becomes the most common cause
      of chronic liver disease , but its prevalence in developing countries like India is also
      increasing (10 -20%).Till date, there is no US-FDA approved therapy for NAFLD but drugs like
      metformin, pioglitazone, sitagliptin, vildagliptin Vitamin E, silymarin, statins and
      ezetimibe have been studied along with life style modification. Life style modifications is
      the current modality of treatment of NAFLD. All the above-mentioned drugs have some
      beneficial effects with limited use due to its adverse effects in patients of NAFLD and the
      study results are non-conclusive. In this scenario, a safe hepatoprotective drug to be
      evaluated in NAFLD.Alpha-lipoic acid (ALA) or 6,8-thioctic acid, is an endogenous molecule
      which functions as an important co-factor for various enzyme complexes in mitochondria and
      plays an important role in energy metabolism. ALA is a nutraceutical agent which also has
      hepatoprotective and anti-inﬂammatory effects.ALA is a nutraceutic having anti-inflammatory
      and antioxidant effects and also increasing insulin sensitivity with lesser adverse effects.
      The relative scarcity of a promising therapy and non-conclusiveness of the previous studies
      open up an arena of further research using a nutraceutic in non-diabetic NAFLD. So, the
      present study is designed to evaluate safety and efficacy of ALA in non-diabetic NAFLD
      patients.
In developed counties Non-alcoholic fatty liver disease (NAFLD) becomes the most common cause
      of chronic liver disease , but its prevalence in developing countries like India is also
      increasing (10 -20%). Most of the patients are diagnosed clinically and by increased serum
      transaminase and fatty changes in liver on abdominal ultrasound. Till date, there is no
      US-FDA approved therapy for NAFLD but drugs like metformin, pioglitazone, sitagliptin,
      vildagliptin Vitamin E, silymarin, statins and ezetimibe have been studied along with life
      style modification. Life style modifications is the current modality of treatment of NAFLD.
      All the above-mentioned drugs have some beneficial effects with limited use due to its
      adverse effects in patients of NAFLD and the study results are non-conclusive. In this
      scenario, a safe hepatoprotective drug to be evaluated in NAFLD.

      Alpha-lipoic acid (ALA) or 6,8-thioctic acid, is an endogenous molecule which functions as an
      important co-factor for various enzyme complexes in mitochondria and plays an important role
      in energy metabolism. ALA is a nutraceutical agent which also has hepatoprotective and
      anti-inﬂammatory effects. Previous animal studies proved the hepatoprotective effect of alpha
      lipoic acid on various animal models. Inflammatory liver injury involves the production of
      inflammatory mediators like nitric oxide and TNF-alpha. Alpha -Lipoic acid significantly
      inhibits production of nitric oxide and TNF-alpha. The reduced production of nitric oxide and
      TNF-alpha in Kupffer cells may be involved in the hepatoprotective action conveyed by
      alpha-lipoic acid.It has been proved that ALA has potent anti - inflammatory and anti-
      oxidant properties.

      Insulin resistance is associated with impaired hepatic cell damage, intrahepatic cholestasis,
      atherogenic dyslipidaemia and fibrosis in patients of NAFLD. Daily treatment with ALA for 28
      days significantly improved insulin sensitivity performance in mice by decreasing insulin
      resistance, IL-6 levels, acetylcholinesterase enzyme activity and oxidative stress in liver.
      Various studies have shown that the ALA can efficiently improve insulin sensitivity and
      reverse the insulin resistance. Cytokeratin 18 (CK 18) is released into circulation as a
      consequence of oxidative stress, hepatocyte apoptosis or inflammation in response to lipid
      metabolism in NAFLD. CK - 18 level is higher in insulin resistance.

      ALA is a nutraceutic having anti-inflammatory and antioxidant effects and also increasing
      insulin sensitivity with lesser adverse effects. The relative scarcity of a promising therapy
      and non-conclusiveness of the previous studies open up an arena of further research using a
      nutraceutic in non-diabetic NAFLD. So, the present study is designed to evaluate safety and
      efficacy of ALA in non-diabetic NAFLD patients.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: A randomized, parallel design placebo-controlled clinical trial
primary purpose: Treatment
masking: Double (Participant, Care Provider)
masking description: The patients and the physician will be blinded
measure: Abdominal ultrasound
time frame: 12 weeks
description: the change in fatty liver grading in NAFLD assessed by abdominal ultrasound
measure: Insulin resistance
time frame: 12 weeks
description: changes in insulin resistance by using HOMA IR after therapy
measure: Lipid profile
time frame: 12 weeks
description: Change in lipid profile (Total Cholesterol, HDL, LDL,Triglycerides, VLDL) after therapy
•
measure: Levels of glutathione reductase
time frame: 12 weeks
description: changes in levels of glutathione reductase after therapy
measure: levels of Cytokeratin-18
time frame: 12 weeks
description: changes in levels of Cytokeratin-18 after therapy
measure: Levels of Alanine transaminase (ALT)
time frame: 12 weeks
description: changes in Alanine transaminase units per litre after therapy
measure: Levels of Aspartate transaminase (AST)
time frame: 12 weeks
description: changes in Aspartate transaminase (AST)units per litre after therapy
measure: Levels of Alkaline phosphatase (ALP)
time frame: 12 weeks
description: changes in Alkaline phosphatase (ALP) in IU after therapy
measure: Levels of Albumin and total protein.
time frame: 12 weeks
description: changes in Albumin and total protein in gm/L after therapy
measure: Levels of Bilirubin
time frame: 12 weeks
description: changes in Bilirubin in μmol/L after therapy
measure: Levels of total protein
time frame: 12 weeks
description: changes in total protein in gm/L after therapy
measure: Levels of Gamma-glutamyltransferase (GGT).
time frame: 12 weeks
description: changes in Gamma-glutamyltransferase (GGT) units per liter after therapy
measure: Levels of L-lactate dehydrogenase (LDH).
time frame: 12 weeks
description: changes in L-lactate dehydrogenase (LDH) units per liter after therapy
arm group label: Placebo
arm group type: Placebo Comparator
description: Life style modification with the placebo will be given for 12 weeks
arm group label: Alphalipoic acid
arm group type: Experimental
description: Life style modification with Alpha lipoic acid in a dose of 600mg twice daily will be prescribed orally for 12 weeks
intervention type: Drug
intervention name: Placebo
description: Lifestyle modification with placebo for 12 weeks
arm group label: Placebo
intervention type: Drug
intervention name: Alphalipoic acid
description: Lifestyle modification with Alphalipoic acid for 12 weeks
arm group label: Alphalipoic acid
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Rituparna Maiti, MD
role: Study Director
affiliation: Additional Professor
last name: Monalisa Jena, MD
phone: 9438884193
email: drmonalisajena@gmail.com
last name: Rituparna Maiti, MD
phone: 9438884191
email: pharm_rituparna@aiimsbhubaneswar.edu.in
facility: 
status: Recruiting
contact: 
contact backup: 
country: India
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PMID: 28976801
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PMID: 29879626
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PMID: 29233029
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PMID: 25543522
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PMID: 28326329
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PMID: 28698650
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PMID: 26550680
responsible party type: Principal Investigator
investigator affiliation: All India Institute of Medical Sciences, Bhubaneswar
investigator full name: Dr. Monalisa Jena, M.D.
investigator title: Associate Professor
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
mesh term: Thioctic Acid
sharing ipd: No