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)

January 24, 2021 updated by: Asian Institute of Gastroenterology, India
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

250

Phase

  • Phase 3

Contacts and Locations

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

Study Locations

  • India
    • Telangana
      • Hyderabad, Telangana, India, 500089
        • Recruiting
        • Asian Institute of Gastroenterology Hospitals
        • Sub-Investigator:
          • Syeda Fatima Sultana, Pharm D

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 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 1. 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).

    1. There is hepatic steatosis by imaging or histology,
    2. There is no significant alcohol consumption,
    3. There are no competing etiologies for hepatic steatosis

    4. 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.

      4. 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:

      1. 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.

      2. 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.
      3. 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.
      4. History of other chronic liver disease (Viral hepatitis B or C, autoimmune hepatitis, cholestatic and metabolic liver diseases) and hemochromatosis.
      5. Patient has known cirrhosis (compensated /decompensated) either based on clinical criteria or liver histology or Imaging techniques.
      6. Patients with Hypothyroidism.

      7. 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
      8. History of myopathies or evidence of active muscle disease.
      9. History of malignancy in the past 5 years and/or active neoplasm with the exception of resolved superficial non-melanoma skin cancer.
      10. Participation in any other therapeutic clinical study in the past 3 months, including participation in any other NAFLD clinical trials.
      11. History of bladder disease and/or hematuria or has current hematuria except due to a urinary tract infection.
      12. Illicit substance abuse within the past 12 months.
      13. 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).
      15. Patients who will not comply with diet and lifestyle changes can be excluded from the final analysis.

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: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Saraglitazar
Patients will receive Saraglitazar 4 mg once daily for 6 months
Drug: Saroglitazar
Patient receives Saraglitazar 4mg once daily
Experimental: Vitamin E
Patients will receive Vitamin E 400mg twice daily for 6 months
Drug: Vitamin E
Patient receive Vitamin E 400mg twice daily after food for 6 months
Experimental: Combination
Patients will receive combination of Saraglitazar 4 mg once daily and Vitamin E 400mg twice daily for 6 months
Drug: Combination drug
Patient receives Vitamine E 400mg twice daily and Saraglitazar 4 mg once daily for 6 months
Active Comparator: Lifestyle
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
Patients receives dietary advise and does exercise in form of aerobic and targets 7 to 10 percent weight loss in 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Non alcoholic fatty liver fibrosis score at 8week, 16week and 24week.
Time Frame: 6 months

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum Alanine aminotransferase (ALT) changes at 6 months.
Time Frame: 6 months
Changes in Alanine aminotransferase at 6 months would be assessed.
6 months
Serum triglycerides (TG) level.
Time Frame: 6 months
Improvement as evidenced by decrease in triglyceride at 6 months.
6 months
Change in fibrosis on Liver Biopsy at 6 months.
Time Frame: 6 months

The study involves a paired liver biopsy and patients who undergo the second biopsy will be assessed for regression or decrease in fibrosis and steatosis score on biopsy.

Score interpretation:

Steatosis: < 5%- 0, 5-33%- 1, >33-66%- 2, >66%- 3. Fibrosis: F0- No fibrosis, F1- Mild fibrosis, F2- Moderate fibrosis, F3- Severe fibrosis
6 months
Serum Aspartate aminotransferase (AST) level at 6 months.
Time Frame: 6 months
Changes in Aspartate aminotransferase at 6 months would be assessed.
6 months
Non alcoholic steatosis (NAS) score on liver biopsy at 6 months.
Time Frame: 6 months

Change in Non alcoholic Steatosis (NAS) score at 6 months. NAS score interpretation: Range- 0 to 8

≥5- Non-alcoholic steatohepatitis (NASH)
6 months
Glycosylated Hemoglobin (HbA1C) Level at 6 months.
Time Frame: 6 months
Change in glycosylated hemoglobin level (amount of glucose attached to hemoglobin) from baseline and at 6 months.
6 months

Collaborators and Investigators

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

Sponsor

Asian Institute of Gastroenterology, India

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 (Anticipated)

January 31, 2021

Primary Completion (Anticipated)

September 30, 2021

Study Completion (Anticipated)

October 31, 2021

Study Registration Dates

First Submitted

August 14, 2019

First Submitted That Met QC Criteria

December 8, 2019

First Posted (Actual)

December 11, 2019

Study Record Updates

Last Update Posted (Actual)

January 26, 2021

Last Update Submitted That Met QC Criteria

January 24, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ECR/346/Inst/AP/2013/RR-16

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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