A Randomized,Placebo-controlled,Double-blind Trial of Phyllanthus Urinaria (Hepaguard®) in Adults With Nonalcoholic Steatohepatitis
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Histologic NAFLD activity score
Study Overview
Brief Summary
Nonalcoholic fatty liver disease is one of the most common chronic liver diseases worldwide. Nonalcoholic steatohepatitis (NASH) is the active form of the disease which runs a progressive course and may result in liver cirrhosis and liver cancer. However, there is yet proven treatment for this disorder. In cell line and animal studies, we have shown that Phyllanthus urinaria can ameliorate NASH by reducing oxidative stress and lipid accumulation. Phyllanthus (Hepaguard) has been used widely by patients with chronic liver diseases, but the efficacy in NASH has not been confirmed in humans.
This study is divided into two parts. In part 1, 60 patients with histology-confirmed NASH will be randomized to receive Hepaguard or placebo for 24 weeks to test the efficacy. Endpoints will be assessed at week 24. The aim of part 2 is to test the durability of Hepaguard. Forty patients originally on Hepaguard will be randomized again to continue Hepaguard for another 24 weeks or stop the treatment. The endpoints at week 48 will be further analyzed.
Detailed Description
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in affluent countries. Patients with nonalcoholic steatohepatitis (NASH), a severe form of NAFLD characterized by ballooning, lobular inflammation and liver fibrosis, have increased mortality rate and risk of cardiovascular disease. Besides, some patients progress to cirrhosis and may even develop hepatocellular carcinoma. In long-term studies, up to 13% of NAFLD patients died of hepatic complications.(1)
Owing to westernization of lifestyle, NAFLD is also increasing dramatically in Asia. In a population screening study in Shanghai using ultrasonography, 15% of adult Chinese was found to suffer from NAFLD.(2) Among Chinese patients with NAFLD, significant necroinflammation and liver fibrosis are not uncommon.(3-5) These patients also often have progression of liver fibrosis with time.(6)
Since NASH is closely related to type 2 diabetes and obesity, a logical approach would be to improve these metabolic parameters.(7, 8) Observational studies suggest that regular exercise and weight reduction benefit NASH patients. At present, there is no registered drug for the treatment of NASH. Although insulin sensitizers such as pioglitazone and rosiglitazone may improve the metabolic profile and hepatic necroinflammation,(9, 10) the effects are not durable.(11) Weight gain and cardiovascular complications also limit the use of these agents.(12, 13) More effective and better tolerated treatment is urgently needed.
Phyllanthus urinaria (Hepaguard®) is commonly used by patients with various chronic liver diseases.(14-16) Phyllanthus has excellent safety profile. In in vitro and in vivo models of NAFLD, Phyllanthus reduces hepatic steatosis, necroinflammation and fibrosis.(16) Oxidative stress and lipid accumulation are ameliorated. Whether the same beneficial effects apply to humans is unclear.
References:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age 18 years or above,
- •Histologic NAFLD activity score 3,
- •Written informed consent
Exclusion Criteria
- •Positive hepatitis B surface antigen, or anti-hepatitis C virus antibody, or histologic features of an alternative liver disease,
- •Alcohol consumption above 30g per week in men or 20g per week in women,
- •Serum alanine aminotransferase above 10 times the upper limit of normal,
- •Liver decompensation,
- •Evidence of hepatocellular carcinoma currently or in the past 5 years,
- •Type 1 diabetes or insulin treatment,
- •Use of investigational drugs in the last 12 weeks,
- •Terminal illness or cancer
Arms & Interventions
Hepaguard
Intervention: Phyllanthus urinaria (Drug)
Placebo
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Histologic NAFLD activity score
Time Frame: week 24
Secondary Outcomes
- ALT normalization(week 24 & week 48)
- Metabolic endpoints(Weeks 12, 24, 36 and 48)
- Changes in magnetic resonance spectroscopy(Weeks 24 and 48)
- Liver stiffness measurement(Weeks 24 and 48)
- Biomarkers of NASH and liver fibrosis(Weeks 12, 24, 36 and 48)
Investigators
Henry LY Chan
Professor
Chinese University of Hong Kong