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Effect of Alpha Lipoic Acid on Non-alcoholic Fatty Liver Diseases

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ClinicalTrials.gov Identifier: NCT04475276
Recruitment Status : Recruiting
First Posted : July 17, 2020
Last Update Posted : July 7, 2021
Sponsor:
Information provided by (Responsible Party):
Dr. Monalisa Jena, M.D., All India Institute of Medical Sciences, Bhubaneswar

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Non-Alcoholic Fatty Liver Disease Drug: Placebo Drug: Alphalipoic acid Phase 4

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A randomized, parallel design placebo-controlled clinical trial
Masking: Double (Participant, Care Provider)
Masking Description: The patients and the physician will be blinded
Primary Purpose: Treatment
Official Title: Effect of Alpha Lipoic Acid on Non-alcoholic Fatty Liver Diseases: A Randomized Placebo-controlled Clinical Trial
Actual Study Start Date : February 23, 2021
Estimated Primary Completion Date : May 31, 2022
Estimated Study Completion Date : July 31, 2022


Arm Intervention/treatment
Placebo Comparator: Placebo
Life style modification with the placebo will be given for 12 weeks
Drug: Placebo
Lifestyle modification with placebo for 12 weeks

Experimental: Alphalipoic acid
Life style modification with Alpha lipoic acid in a dose of 600mg twice daily will be prescribed orally for 12 weeks
Drug: Alphalipoic acid
Lifestyle modification with Alphalipoic acid for 12 weeks




Primary Outcome Measures :
  1. Abdominal ultrasound [ Time Frame: 12 weeks ]
    the change in fatty liver grading in NAFLD assessed by abdominal ultrasound


Secondary Outcome Measures :
  1. Insulin resistance [ Time Frame: 12 weeks ]
    changes in insulin resistance by using HOMA IR after therapy

  2. Lipid profile [ Time Frame: 12 weeks ]

    Change in lipid profile (Total Cholesterol, HDL, LDL,Triglycerides, VLDL) after therapy


  3. Levels of glutathione reductase [ Time Frame: 12 weeks ]
    changes in levels of glutathione reductase after therapy

  4. levels of Cytokeratin-18 [ Time Frame: 12 weeks ]
    changes in levels of Cytokeratin-18 after therapy

  5. Levels of Alanine transaminase (ALT) [ Time Frame: 12 weeks ]
    changes in Alanine transaminase units per litre after therapy

  6. Levels of Aspartate transaminase (AST) [ Time Frame: 12 weeks ]
    changes in Aspartate transaminase (AST)units per litre after therapy

  7. Levels of Alkaline phosphatase (ALP) [ Time Frame: 12 weeks ]
    changes in Alkaline phosphatase (ALP) in IU after therapy

  8. Levels of Albumin and total protein. [ Time Frame: 12 weeks ]
    changes in Albumin and total protein in gm/L after therapy

  9. Levels of Bilirubin [ Time Frame: 12 weeks ]
    changes in Bilirubin in μmol/L after therapy

  10. Levels of total protein [ Time Frame: 12 weeks ]
    changes in total protein in gm/L after therapy

  11. Levels of Gamma-glutamyltransferase (GGT). [ Time Frame: 12 weeks ]
    changes in Gamma-glutamyltransferase (GGT) units per liter after therapy

  12. Levels of L-lactate dehydrogenase (LDH). [ Time Frame: 12 weeks ]
    changes in L-lactate dehydrogenase (LDH) units per liter after therapy



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All patients diagnosed to have fatty liver grading 1, 2, 3 on abdominal ultrasound, mild to moderate elevation (<5 times elevated upper limit) of serum aminotransferase level.
  • Patients aged 18-65 years of either sex.
  • Treatment naïve patients or patients who had not taken any treatment for at least 4 weeks before inclusion

Exclusion Criteria:

  • History of diabetes mellitus, decompensated liver disease, ascites, oesophageal varices.
  • Drug abusers and Alcoholics.
  • HBs Ag positive, Anti HCV and HIV, hereditary defects of iron, copper and alpha- 1 antitrypsin deficient patients.
  • Hypothyroidism, obstructive sleep apnoea, total parenteral nutrition, short bowel syndrome, pancreatoduodenal resection which are secondary causes of NAFLD.
  • Drug users such as corticosteroids, antiviral (nucleoside analogue), tetracycline, methotrexate, tamoxifen and amiodarone.
  • Patients who are taking any antihyperlipidemic and anti-diabetic agents.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04475276


Contacts
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Contact: Monalisa Jena, MD 9438884193 drmonalisajena@gmail.com
Contact: Rituparna Maiti, MD 9438884191 pharm_rituparna@aiimsbhubaneswar.edu.in

Locations
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India
AIIMS Recruiting
Bhubaneswar, Odisha, India, 751019
Contact: Monalisa Jena, MD    9438884193    drmonalisajena@gmail.com   
Contact: Rituparna Maiti, MD    9438884191    pharm_rituparna@aiimsbhubaneswar.edu.in   
Sponsors and Collaborators
All India Institute of Medical Sciences, Bhubaneswar
Investigators
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Study Director: Rituparna Maiti, MD Additional Professor
Publications of Results:

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Responsible Party: Dr. Monalisa Jena, M.D., Associate Professor, All India Institute of Medical Sciences, Bhubaneswar
ClinicalTrials.gov Identifier: NCT04475276    
Other Study ID Numbers: T/IM-F/19-20/16
First Posted: July 17, 2020    Key Record Dates
Last Update Posted: July 7, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dr. Monalisa Jena, M.D., All India Institute of Medical Sciences, Bhubaneswar:
Non alcoholic fatty liver
Alphalipoic acid
Nutraceutic
Insulin resistance
Cytokeratin 18
Life style modification
Vitamin E
Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases
Thioctic Acid
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients