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

All India Institute of Medical Sciences, Bhubaneswar

Status and phase: Enrolling; Phase 4

Conditions: Non-Alcoholic Fatty Liver Disease

Treatments: Drug: Placebo; Drug: Alphalipoic acid

Study type: Interventional

Funder types: Other

Identifiers

NCT04475276

T/IM-F/19-20/16

Details and patient eligibility

About

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.

Full 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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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120 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Life style modification with the placebo will be given for 12 weeks

Treatment:

Drug: Placebo

Alphalipoic acid

Experimental group

Description:

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

Treatment:

Drug: Alphalipoic acid