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

Sponsor

All India Institute of Medical Sciences, Bhubaneswar (Other)

Overall Status

Recruiting

CT.gov ID

NCT04475276

Collaborator

(none)

120

Enrollment

Location

Arms

17.2

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

A randomized, parallel design placebo-controlled clinical trialA 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 :

Feb 23, 2021

Anticipated Primary Completion Date :

May 31, 2022

Anticipated Study Completion Date :

Jul 31, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Abdominal ultrasound [12 weeks]
the change in fatty liver grading in NAFLD assessed by abdominal ultrasound

Secondary Outcome Measures

Insulin resistance [12 weeks]
changes in insulin resistance by using HOMA IR after therapy
Lipid profile [12 weeks]
Change in lipid profile (Total Cholesterol, HDL, LDL,Triglycerides, VLDL) after therapy •
Levels of glutathione reductase [12 weeks]
changes in levels of glutathione reductase after therapy
levels of Cytokeratin-18 [12 weeks]
changes in levels of Cytokeratin-18 after therapy
Levels of Alanine transaminase (ALT) [12 weeks]
changes in Alanine transaminase units per litre after therapy
Levels of Aspartate transaminase (AST) [12 weeks]
changes in Aspartate transaminase (AST)units per litre after therapy
Levels of Alkaline phosphatase (ALP) [12 weeks]
changes in Alkaline phosphatase (ALP) in IU after therapy
Levels of Albumin and total protein. [12 weeks]
changes in Albumin and total protein in gm/L after therapy
Levels of Bilirubin [12 weeks]
changes in Bilirubin in μmol/L after therapy
Levels of total protein [12 weeks]
changes in total protein in gm/L after therapy
Levels of Gamma-glutamyltransferase (GGT). [12 weeks]
changes in Gamma-glutamyltransferase (GGT) units per liter after therapy
Levels of L-lactate dehydrogenase (LDH). [12 weeks]
changes in L-lactate dehydrogenase (LDH) units per liter after therapy

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.