Treatment of nonalcoholic fatty liver using different types of medicines and lifestyle changes

Phase 3

Not yet recruiting

Conditions: Fatty (change of) liver, not elsewhere classified,

Registration Number: CTRI/2019/12/022339

Lead Sponsor: Asian Institute of Gastroenterology

Brief Summary: Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease. The severity of NAFLD ranges from relatively benign simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is characterized by hepatocellular injury, inflammation and risk of progression to cirrhosis with complications of portal hypertension, liver failure and hepatocellular carcinoma. Nonalcoholic steatohepatitis is considered a hepatic manifestation of the metabolic syndrome. In many patients, insulin resistance underlies the development of the metabolic syndrome; consequently, NASH is highly prevalent among patients with type 2 diabetes mellitus (T2DM). Currently, obesity and associated T2DM have reached epidemic proportions and are considered burgeoning public health problems.

Saroglitazar, [benzenepropanoic acid, Î±-ethoxy-4-[2-[2-methyl-5-[4-(methylthio) phenyl]-1Hpyrrol- 1yl]ethoxy]- , magnesium salt (2:1), (Î±S)], is a novel peroxisome proliferator activated receptor (PPAR) agonist with dual PPAR agonistic properties â€“ it is a potent and predominant PPARÎ± agonist with moderate PPARÎ³ agonistic activity. Saroglitazar has been the first glitazar granted marketing authorization in India and is indicated for treatment of diabetic Dyslipidemia. The drug was developed with an expectation to achieve optimum anti-dyslipidemia and ant hyperglycemic effects, while avoiding adverse events (AEs) such as peripheral edema, weight gain, cardiovascular events, renal and/or liver toxicity, etc., which are commonly seen with other dual PPAR or PPARÎ± agonists.

Saroglitazar is known to safely and effectively improve Dyslipidemia by reducing triglyceride(TG), low density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL)cholesterol, non-high-density lipoprotein (non-HDL) cholesterol and increasing high density lipoprotein (HDL) cholesterol. In addition, Saroglitazar can improve glycemic indices in diabetic patients by reducing fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c).

Vitamin E consists of two families of compounds, the tocopherols and tocotrienols, characterised by a 6-chromanol ring and an isoprenoid side chain. The members of each family are designated alpha((Î±)-, beta(Î²)-, gamma(Î³)-, or delta(Î´)- according to the position of methyl groups attached to the chroman nucleus. Vitamin Eâ€™s major function appears to be as a non-specific chain-breaking antioxidant that prevents the propagation of free-radical reactions. The vitamin is a peroxyl radical scavenger and especially protects polyunsaturated fatty acids (PUFAs) within membrane phospholipids and in plasma lipoproteins.

Considering the association between insulin resistance, Dyslipidemia and the development of NAFLD/NASH, Saroglitazar could potentially benefit patients with NAFLD including those with borderline NASH. Therefore, the purpose of the present study is to examine the efficacy of Saroglitazar and vitamin E with or without combination in improving NAFLD Fibrosis Score and liver biochemistry in patients with NAFLD/NASH.

In this study we aim to evaluate the hospital based clinic-pathological profile, diagnosis, treatment regimen and follow up of Indian patients with NAFLD/ NASH.

Detailed Description: Not available

Recruitment & Eligibility

Status: Not Yet Recruiting

Sex: All

Target Recruitment: 200

Inclusion Criteria

Adults (age 18 to 60) 2.
Confirmed Diagnosis of NAFLD established either by imaging (ultrasound, CT scan or MRI) or liver biopsy showing simple steatosis, within 6 months of the Screening Phase for this study.
The diagnosis of NAFLD is made according to the American Association for the Study of Liver Diseases (AASLD) criteria (Chalasaniet al.2017).
(a) There is hepatic steatosis by imaging or histology, (b) There is no significant alcohol consumption, (c) There are no competing etiologies for hepatic steatosis (d) There are no co-existing causes for chronic liver disease.
Patientâ€™s demonstration of understanding of study requirements and treatment procedures, willingness to comply with all protocol-required evaluations.
Either take biopsy proven NAFLD or imaging based NAFLD with ALT more than 1.5 times the upper limit of normal.
(being considered as 32) 5.
Liver biopsy would be done in selected cases where the cause of transaminitis was uncertain of possible biopsy would be done on case to case basis.

Exclusion Criteria

Absence of regular or excessive use of alcohol within 2 years prior to initial screening.
Presence of alternative causes of fatty liver.
ïƒ˜ Weight loss >10% in the 6 months before the Screening Visit ïƒ˜ Total parenteral nutrition, starvation or protein-calorie malnutrition ïƒ˜ Use of drugs associated with NAFLD for more than 12 consecutive weeks in the 1 year before start of the study, including amiodarone, tamoxifen, methotrexate, systemic glucocorticoids, anabolic steroids, tetracycline, estrogens in doses higher than used in oral contraceptives, vitamin A, L asparaginase, valproate, chloroquine, or antiretroviral drugs.
History of bowel surgery, gastrointestinal (bariatric) surgery or undergoing evaluation for bariatric surgery for obesity, extensive small-bowel resection, or orthotopic liver transplants (OLT) or listed for OLT.
History of other chronic liver disease (Viral hepatitis B or C, autoimmune hepatitis, cholestatic and metabolic liver diseases) and hemochromatosis.
Patient has known cirrhosis (compensated /decompensated) either based on clinical criteria or liver histology or Imaging techniques.
Patients with Hypothyroidism.
Patients with unstable cardiovascular disease including, ïƒ˜ unstable angina, (i.e., new or worsening symptoms of coronary heart disease within the past 3 months), acute coronary syndrome within the past 6 months, acute myocardial infarction in the past 3 months or heart failure of New York Heart Association class (III â€“ IV) or worsening congestive heart failure, or coronary artery intervention, within the past 6 months ïƒ˜ history of (within prior 3 months) or current unstable cardiac dysarrhythmias ïƒ˜ uncontrolled hypertension (systolic BP>180 mmHg and/or diastolic BP >110 mmHg on two consecutive occasions) ïƒ˜ stroke or transient ischemic attack within the prior 6 months 8.
History of myopathies or evidence of active muscle disease.
History of malignancy in the past 5 years and/or active neoplasm with the exception of resolved superficial non-melanoma skin cancer.
Participation in any other therapeutic clinical study in the past 3 months, including participation in any other NAFLD clinical trials.
History of bladder disease and/or hematuria or has current hematuria except due to a urinary tract infection.
Illicit substance abuse within the past 12 months.
Pregnant/lactating female (including positive pregnancy test at the Screening Visit) 14.
History or other evidence of severe illness or any other conditions that would make the patient, in the opinion of the investigator, unsuitable for the study (such as poorly controlled psychiatric disease, HIV, coronary artery disease or active gastrointestinal conditions that might interfere with drug absorption).
Patients who will not comply with diet and lifestyle changes can be excluded from the final analysis.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1. Change in NAFLD fibrosis score at 8week, 16week and 24week.	2 month, 4 month, 6 month
2. Compare the overall efficacy of patients with NAFLD/ NASH treated with Saroglitazar magnesium, vitamin E and Saroglitazar magnesium with Vitamin E and Life style modifications alone.	2 month, 4 month, 6 month
3. Determine the safety profile of these regimens in those patients.	2 month, 4 month, 6 month

Secondary Outcome Measures

Name	Time	Method
1. Serum alanine aminotransferase (ALT) & aspartate aminotransferase (AST) level.	2. Serum triglycerides (TG) level, high-density lipoprotein (HDL), low density lipoprotein (LDL) & fasting plasma glucose (FPG)/glycosylated haemoglobin (HbA1c).

Trial Locations

Locations (1): Asian Institute of Gastroenterology
🇮🇳
Hyderabad, TELANGANA, India
Asian Institute of Gastroenterology
🇮🇳Hyderabad, TELANGANA, India
Mithun Sharma
Principal investigator
08790622655
drmithunsharma@gmail.com