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Polypill and Nonalcoholic Steatohepatitis (PolyIran-Liver)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Tehran University of Medical Sciences
ClinicalTrials.gov Identifier:
NCT01245608
First received: November 19, 2010
Last updated: June 25, 2012
Last verified: June 2012
History of Changes
  Purpose

Polypill, which is being studied as an agent able to prevent cardiovascular events, contains atorvastatin and valsartan which might have beneficial effects in nonalcoholic steatohepatitis (NASH). This study aims to evaluate the possible benefits of polypill in NASH. Furthermore, cardiovascular mortality is a major cause of mortality in NASH patients. Polypill is expected to reduce cardiovascular mortality. We believe polypill is beneficial to patients with NASH by both preventing cardiovascular mortality and by improving liver condition.


Condition Intervention Phase
Nonalcoholic Steatohepatitis
 Drug: Polypill
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effect of Polypill on the Natural History of Nonalcoholic Steatohepatitis

Further study details as provided by Tehran University of Medical Sciences:

Primary Outcome Measures:
  • Changes in liver stiffness [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    As measured by Fibroscan


Secondary Outcome Measures:
  • Side effects [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Changes in liver enzyme levels [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Cardiovascular events [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Includes myocardial infarction, cerebrovascular accident, sudden cardiac death, hospital admission due to cardiovascular events

  • Compliance [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Percent of pills taken


Estimated Enrollment: 1500
Study Start Date: October 2011
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Polypill Drug: Polypill
Polypill taken once daily for 5 years. Each pill contains ASA 81 mg, atorvastatin 20 mg, hydrochlorothiazide 12.5 mg, valsartan 40 mg
No Intervention: Control

Detailed Description:

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of disease ranging from steatosis to steatohepatitis (nonalcoholic steatohepatitis, NASH) to cirrhosis. Statins are competitive inhibitors of HMG CoA reductase, the rate-limiting step in cholesterol biosynthesis. They occupy a portion of the binding site of HMG CoA, blocking access of this substrate to the active site on the enzyme. A reduction in intrahepatic cholesterol leads to an increase in LDL receptor turnover that results from an enhanced rate of hepatic LDL receptor cycling. On the other hand recent studies have implicated several important cellular processes and signaling pathways that are affected by abnormal lipid metabolism, resulting in specific biochemical, histological, and clinical changes associated with NAFLD.

Maybe statins, as lipid lowering agents, and through their effect in reduction of intrahepatic cholesterol, can affect the abnormal lipid metabolism in NASH.

Angiotensin II could also promote fibrogenesis and inhibitors such as ARBs and ACE inhibitors might help halt the progression of NASH.

ASA and hydrocholorthiazide, other components of polypill, can help prevent cardiovascular morbidity and mortality which is increased in NASH.

  Eligibility

Ages Eligible for Study:   50 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • NASH diagnosed on the basis of the following criteria:

    1. Imaging techniques showing evidence of hepatic steatosis
    2. Increased AST or ALT to above 1.5 times normal

Exclusion Criteria:

  • Patients with the diagnosis hepatitis B, hepatitis C, autoimmune hepatitis, and genetic liver disease, such as Wilson's disease and hemochromatosis.
  • Participants presenting one or more causes commonly associated with secondary NAFLD (drugs, surgical procedures, environmental toxins, or total parenteral nutrition)
  • Alcohol ingestion greater than 40gr per week
  • Not consenting to the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01245608

Locations
Iran, Islamic Republic of
Golestan Cohort Center
Gonbad, Golestan, Iran, Islamic Republic of
Sponsors and Collaborators
Tehran University of Medical Sciences
Investigators
Study Chair: Reza Malekzadeh, M.D. Tehran University of Medical Sciences
Principal Investigator: Shahin Merat, M.D. Tehran University of Medical Sciences
  More Information

No publications provided

Responsible Party: Tehran University of Medical Sciences
ClinicalTrials.gov Identifier: NCT01245608     History of Changes
Other Study ID Numbers: DDRI/90.22
Study First Received: November 19, 2010
Last Updated: June 25, 2012
Health Authority: Iran: Ministry of Health

Keywords provided by Tehran University of Medical Sciences:
Atorvastatin
Statins
nonalcoholic steatohepatitis
 fatty liver
nonalcoholic fatty liver disease
lipid lowering agents

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on May 21, 2013