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

December 12, 2023 updated by: Dr. Monalisa Jena, M.D., All India Institute of Medical Sciences, Bhubaneswar

Effect of Alpha Lipoic Acid on Non-alcoholic Fatty Liver Diseases: A Randomized Placebo-controlled Clinical Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Abdominal ultrasound
Time Frame: 12 weeks
the change in fatty liver grading in NAFLD assessed by abdominal ultrasound
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Insulin resistance
Time Frame: 12 weeks
changes in insulin resistance by using HOMA IR after therapy
12 weeks
Lipid profile
Time Frame: 12 weeks

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

•
12 weeks
Levels of glutathione reductase
Time Frame: 12 weeks
changes in levels of glutathione reductase after therapy
12 weeks
levels of Cytokeratin-18
Time Frame: 12 weeks
changes in levels of Cytokeratin-18 after therapy
12 weeks
Levels of Alanine transaminase (ALT)
Time Frame: 12 weeks
changes in Alanine transaminase units per litre after therapy
12 weeks
Levels of Aspartate transaminase (AST)
Time Frame: 12 weeks
changes in Aspartate transaminase (AST)units per litre after therapy
12 weeks
Levels of Alkaline phosphatase (ALP)
Time Frame: 12 weeks
changes in Alkaline phosphatase (ALP) in IU after therapy
12 weeks
Levels of Albumin and total protein.
Time Frame: 12 weeks
changes in Albumin and total protein in gm/L after therapy
12 weeks
Levels of Bilirubin
Time Frame: 12 weeks
changes in Bilirubin in μmol/L after therapy
12 weeks
Levels of total protein
Time Frame: 12 weeks
changes in total protein in gm/L after therapy
12 weeks
Levels of Gamma-glutamyltransferase (GGT).
Time Frame: 12 weeks
changes in Gamma-glutamyltransferase (GGT) units per liter after therapy
12 weeks
Levels of L-lactate dehydrogenase (LDH).
Time Frame: 12 weeks
changes in L-lactate dehydrogenase (LDH) units per liter after therapy
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

All India Institute of Medical Sciences, Bhubaneswar

Investigators

  • Study Director: Rituparna Maiti, MD, Additional Professor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 23, 2021

Primary Completion (Estimated)

December 31, 2023

Study Completion (Estimated)

December 31, 2023

Study Registration Dates

First Submitted

July 10, 2020

First Submitted That Met QC Criteria

July 15, 2020

First Posted (Actual)

July 17, 2020

Study Record Updates

Last Update Posted (Estimated)

December 13, 2023

Last Update Submitted That Met QC Criteria

December 12, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • T/IM-F/19-20/16

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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