The Effect of Polypill on Patients With Presumed NASH (PolyIran-L)

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: May 6, 2014
Last verified: May 2014
  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 liver-related variables especially in subjects with presumed NASH. Furthermore, cardiovascular mortality is a major cause of mortality in NASH patients or even in subjects with increased liver enzymes. Polypill is expected to reduce cardiovascular mortality. We believe polypill is beneficial to patients with presumed 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: Long-Term Effect of Polypill on Liver Stiffness, Liver Enzymes and Mortality in Subjects With Presumed NASH.

Resource links provided by NLM:


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
Single daily dose of PolyPill and 6-monthly visits
Drug: Polypill
Polypill taken once daily for 5 years. Each pill contains ASA 81 mg, atorvastatin 20 mg, hydrochlorthiazide 12.5 mg, valsartan 40 mg
Other Name: PolyPill 4-2
No Intervention: Control
Only 6-monthly visits

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

Identifying NASH patients without performing liver biopsies is challenging. As we cannot perform liver biopsies on our subjects and ultrasonography misses steatosis in many subjects, we assume subjects with increased liver enzymes not having hepatitis B or C to have "presumed" NASH. We will be comparing the effect of polypill in these subjects with subjects having normal liver enzyme levels and against controls not taking polypill.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

- Being enrolled in Golestan Cohort Study

Exclusion Criteria:

  • Debilitating disease causing inability to comply
  • Contraindications to any of the components of PolyPill
  • Not consenting to the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: May 6, 2014
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

ClinicalTrials.gov processed this record on October 23, 2014