An Investigator Initiated Prospective, Four Arms Randomized Comparative Study of Efficacy and Safety of Saroglitazar, Vitamin E and Life Style Modification in Patients With Nonalcoholic Fatty Liver Disease (NAFLD)/ Non-alcoholic Steatohepatitis (NASH)

NCT04193982 | Unknown Phase 3

• 1 other identifier: ECR/346/Inst/AP/2013/RR-16
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

Saroglitazar and Vitamin E are both being extensively used in India for non alcoholic fatty liver disease, though none of these drugs are FDA approved for this indication.However they are backed up by number of studies which shows improvement in liver function , reduction in NAS score. However, there is no head to head trial , nor is there any study with a paired biopsy comparing two arms for a head to head study. We therefore designed this study to see the effect of Vitamin E vs Vitamin E plus saroglitazar vs Saroglitazar alone when compared to standard dietary and weight loss treatment for NAFLD with raised ALT levels.

Conditions

NAFLD

Keywords

Saraglitazar; Vitamin E

Outcome Measures

Primary Outcomes (1)

• Change in Non alcoholic fatty liver fibrosis score at 8week, 16week and 24week.

  Non alcoholic fatty liver fibrosis score would be assessed . This is a non invasive test calculated by the formula : -1.675 + 0.037 × age (years) + 0.094 × BMI (kg/m2) + 1.13 × IFG/diabetes (yes = 1, no = 0) + 0.99 × AST/ALT ratio - 0.013 × platelet (×109/l) - 0.66 × albumin (g/dl) Results are interpreted as : NAFLD Score \< -1.455 = F0-F2 NAFLD Score -1.455 - 0.675 = indeterminate score NAFLD Score \> 0.675 = F3-F4 Change in the NAFLD fibrosis score from the initiation of treatment and at end of 6 months would be assessed.

  6 months

Secondary Outcomes (6)

• Serum Alanine aminotransferase (ALT) changes at 6 months.

  6 months

• Serum triglycerides (TG) level.

  6 months

• Change in fibrosis on Liver Biopsy at 6 months.

  6 months

• Serum Aspartate aminotransferase (AST) level at 6 months.

  6 months

• Non alcoholic steatosis (NAS) score on liver biopsy at 6 months.

  6 months

Study Arms (4)

Saraglitazar

EXPERIMENTAL

Patients will receive Saraglitazar 4 mg once daily for 6 months

Drug: Saroglitazar

Vitamin E

EXPERIMENTAL

Patients will receive Vitamin E 400mg twice daily for 6 months

Drug: Vitamin E

Combination

EXPERIMENTAL

Patients will receive combination of Saraglitazar 4 mg once daily and Vitamin E 400mg twice daily for 6 months

Drug: Combination drug

Lifestyle

ACTIVE COMPARATOR

Patients will follow instruction from dietician and life style changes advise as per protocol including targeting 7 to 10percent weight loss in 6 months

Behavioral: Lifestyle Changes

Interventions

Saroglitazar DRUG

Patient receives Saraglitazar 4mg once daily

Saraglitazar

Vitamin E DRUG

Patient receive Vitamin E 400mg twice daily after food for 6 months

Vitamin E

Combination drug DRUG

Patient receives Vitamine E 400mg twice daily and Saraglitazar 4 mg once daily for 6 months

Combination

Lifestyle Changes BEHAVIORAL

Patients receives dietary advise and does exercise in form of aerobic and targets 7 to 10 percent weight loss in 6 months

Lifestyle

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \. 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).
• There is hepatic steatosis by imaging or histology,
• There is no significant alcohol consumption,
• There are no competing etiologies for hepatic steatosis
• There are no co-existing causes for chronic liver disease. 3. Patient'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.

You may not qualify if:

• Absence of regular or excessive use of alcohol within 2 years prior to initial screening. History of alcohol will be taken from the patient and one or more family member and patient will be defined as non-alcoholic if he/she is a total abstainer or takes \>20g (males) or 10g (females) of alcohol per day or greater than 14 drinks per week in males or greater than 7 drinks per week in females. Approximately 10 g of alcohol equals one 'drink' unit. One unit equals 30 ml of distilled spirits, 355 ml beer, or 120 ml glass of wine.
• Presence of alternative causes of fatty liver, including:
• Weight loss \>10% in the 6 months before the Screening Visit
• Total parenteral nutrition, starvation or protein-calorie malnutrition
• 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.
• Unstable cardiovascular disease, including:
• 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 - IV) or worsening congestive heart failure, or coronary artery intervention, within the past 6 months
• history of (within prior 3 months) or current unstable cardiac dysarrhythmias
• uncontrolled hypertension (systolic BP\>180 mmHg and/or diastolic BP \>110 mmHg on two consecutive occasions)
• stroke or transient ischemic attack within the prior 6 months
• History of myopathies or evidence of active muscle disease.

Sponsors & Collaborators

• Asian Institute of Gastroenterology, India: lead

Study Sites (1)

Asian Institute of Gastroenterology Hospitals

Hyderabad, Telangana, 500089, India

RECRUITING

Related Publications (5)

• Duseja A, Singh SP, Saraswat VA, Acharya SK, Chawla YK, Chowdhury S, Dhiman RK, Jayakumar RV, Madan K, Misra SP, Mishra H, Modi SK, Muruganathan A, Saboo B, Sahay R, Upadhyay R. Non-alcoholic Fatty Liver Disease and Metabolic Syndrome-Position Paper of the Indian National Association for the Study of the Liver, Endocrine Society of India, Indian College of Cardiology and Indian Society of Gastroenterology. J Clin Exp Hepatol. 2015 Mar;5(1):51-68. doi: 10.1016/j.jceh.2015.02.006. Epub 2015 Mar 6.

  PMID: 25941433 BACKGROUND

• Dhiman RK, Duseja A, Chawla Y. Asians need different criteria for defining overweight and obesity. Arch Intern Med. 2005 May 9;165(9):1069-70. doi: 10.1001/archinte.165.9.1069-b. No abstract available.

  PMID: 15883250 BACKGROUND

• Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ; American Gastroenterological Association; American Association for the Study of Liver Diseases; American College of Gastroenterologyh. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology. 2012 Jun;142(7):1592-609. doi: 10.1053/j.gastro.2012.04.001. Epub 2012 May 15. No abstract available.

  PMID: 22656328 BACKGROUND

• Georgescu EF, Georgescu M. Therapeutic options in non-alcoholic steatohepatitis (NASH). Are all agents alike? Results of a preliminary study. J Gastrointestin Liver Dis. 2007 Mar;16(1):39-46.

  PMID: 17410287 BACKGROUND

• Sanyal AJ, Brunt EM, Kleiner DE, Kowdley KV, Chalasani N, Lavine JE, Ratziu V, McCullough A. Endpoints and clinical trial design for nonalcoholic steatohepatitis. Hepatology. 2011 Jul;54(1):344-53. doi: 10.1002/hep.24376.

  PMID: 21520200 BACKGROUND

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

saroglitazar; Vitamin E; Drug Combinations

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations

Central Study Contacts

Mithun Sharma, MD

CONTACT

8790622655; drmithunsharma@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2019
• First Posted: December 11, 2019
• Study Start: January 31, 2021
• Primary Completion: September 30, 2021
• Study Completion: October 31, 2021
• Last Updated: January 26, 2021

Record last verified: 2021-01

Locations

IN (1)