Trial of Hepaguard® in Adults With Nonalcoholic Steatohepatitis

NCT01210989 | Completed DMC

• 1 other identifier: NAFLD- Hepaguard
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Nonalcoholic Fatty Liver Disease

Outcome Measures

Primary Outcomes (1)

• Histologic NAFLD activity score

  week 24

Secondary Outcomes (5)

• 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

Study Arms (2)

Hepaguard

ACTIVE COMPARATOR

Drug: Phyllanthus urinaria

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Phyllanthus urinaria DRUG

Subjects meeting the inclusion and exclusion criteria will be randomized (2:1) to receive oral Hepaguard 1 g three times daily or placebo of identical appearance. At week 24, subjects receiving active Hepaguard will be randomized (1:1) to continue Hepaguard for another 24 weeks or stop treatment.

Also known as: Hepaguard®

Hepaguard

Placebo DRUG

Subjects meeting the inclusion and exclusion criteria will be randomized (2:1) to receive oral Hepaguard 1 g three times daily or placebo of identical appearance.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or above,
• Histologic NAFLD activity score 3,
• Written informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Cheng Suen Man Shook Hepatitis Center, Institute of Digestive Disease, The Chinese University of Hong Kong, Prince of Wales Hospital

Hong Kong SAR, China

Location

Related Publications (20)

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• Wong VW, Chan HL, Hui AY, Chan KF, Liew CT, Chan FK, Sung JJ. Clinical and histological features of non-alcoholic fatty liver disease in Hong Kong Chinese. Aliment Pharmacol Ther. 2004 Jul 1;20(1):45-9. doi: 10.1111/j.1365-2036.2004.02012.x.

  PMID: 15225170 BACKGROUND

• Wong VW, Wong GL, Chim AM, Tse AM, Tsang SW, Hui AY, Choi PC, Chan AW, So WY, Chan FK, Sung JJ, Chan HL. Validation of the NAFLD fibrosis score in a Chinese population with low prevalence of advanced fibrosis. Am J Gastroenterol. 2008 Jul;103(7):1682-8. doi: 10.1111/j.1572-0241.2008.01933.x. Epub 2008 Jul 4.

  PMID: 18616651 BACKGROUND

• Wong VW, Wong GL, Tsang SW, Hui AY, Chan AW, Choi PC, Chim AM, Chu S, Chan FK, Sung JJ, Chan HL. Metabolic and histological features of non-alcoholic fatty liver disease patients with different serum alanine aminotransferase levels. Aliment Pharmacol Ther. 2009 Feb 15;29(4):387-96. doi: 10.1111/j.1365-2036.2008.03896.x. Epub 2008 Nov 17.

  PMID: 19035982 BACKGROUND

• Hui AY, Wong VW, Chan HL, Liew CT, Chan JL, Chan FK, Sung JJ. Histological progression of non-alcoholic fatty liver disease in Chinese patients. Aliment Pharmacol Ther. 2005 Feb 15;21(4):407-13. doi: 10.1111/j.1365-2036.2005.02334.x.

  PMID: 15709991 BACKGROUND

• Wong VW, Hui AY, Tsang SW, Chan JL, Tse AM, Chan KF, So WY, Cheng AY, Ng WF, Wong GL, Sung JJ, Chan HL. Metabolic and adipokine profile of Chinese patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2006 Sep;4(9):1154-61. doi: 10.1016/j.cgh.2006.06.011. Epub 2006 Aug 14.

  PMID: 16904946 BACKGROUND

• Wong VW, Hui AY, Tsang SW, Chan JL, Wong GL, Chan AW, So WY, Cheng AY, Tong PC, Chan FK, Sung JJ, Chan HL. Prevalence of undiagnosed diabetes and postchallenge hyperglycaemia in Chinese patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2006 Oct 15;24(8):1215-22. doi: 10.1111/j.1365-2036.2006.03112.x.

  PMID: 17014580 BACKGROUND

• Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J, Balas B, Gastaldelli A, Tio F, Pulcini J, Berria R, Ma JZ, Dwivedi S, Havranek R, Fincke C, DeFronzo R, Bannayan GA, Schenker S, Cusi K. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med. 2006 Nov 30;355(22):2297-307. doi: 10.1056/NEJMoa060326.

  PMID: 17135584 BACKGROUND

• Ratziu V, Giral P, Jacqueminet S, Charlotte F, Hartemann-Heurtier A, Serfaty L, Podevin P, Lacorte JM, Bernhardt C, Bruckert E, Grimaldi A, Poynard T; LIDO Study Group. Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial. Gastroenterology. 2008 Jul;135(1):100-10. doi: 10.1053/j.gastro.2008.03.078. Epub 2008 Apr 8.

  PMID: 18503774 BACKGROUND

• Lutchman G, Modi A, Kleiner DE, Promrat K, Heller T, Ghany M, Borg B, Loomba R, Liang TJ, Premkumar A, Hoofnagle JH. The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis. Hepatology. 2007 Aug;46(2):424-9. doi: 10.1002/hep.21661.

  PMID: 17559148 BACKGROUND

• Juurlink DN, Gomes T, Lipscombe LL, Austin PC, Hux JE, Mamdani MM. Adverse cardiovascular events during treatment with pioglitazone and rosiglitazone: population based cohort study. BMJ. 2009 Aug 18;339:b2942. doi: 10.1136/bmj.b2942.

  PMID: 19690342 BACKGROUND

• Wang M, Cheng H, Li Y, Meng L, Zhao G, Mai K. Herbs of the genus Phyllanthus in the treatment of chronic hepatitis B: observations with three preparations from different geographic sites. J Lab Clin Med. 1995 Oct;126(4):350-2.

  PMID: 7561442 BACKGROUND

• Chan HL, Sung JJ, Fong WF, Chim AM, Yung PP, Hui AY, Fung KP, Leung PC. Double-blinded placebo-controlled study of Phyllanthus urinaris for the treatment of chronic hepatitis B. Aliment Pharmacol Ther. 2003 Aug 1;18(3):339-45. doi: 10.1046/j.1365-2036.2003.01671.x.

  PMID: 12895219 BACKGROUND

• Shen B, Yu J, Wang S, Chu ES, Wong VW, Zhou X, Lin G, Sung JJ, Chan HL. Phyllanthus urinaria ameliorates the severity of nutritional steatohepatitis both in vitro and in vivo. Hepatology. 2008 Feb;47(2):473-83. doi: 10.1002/hep.22039.

  PMID: 18157836 BACKGROUND

• Ekstedt M, Franzen LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G, Kechagias S. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006 Oct;44(4):865-73. doi: 10.1002/hep.21327.

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• Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ; Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005 Jun;41(6):1313-21. doi: 10.1002/hep.20701.

  PMID: 15915461 BACKGROUND

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  PMID: 17393509 BACKGROUND

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  PMID: 16729309 BACKGROUND

• Wong VW, Wong GL, Chan AW, Chu WC, Choi PC, Chim AM, Yiu KK, Yu J, Chan FK, Chan HL. Treatment of non-alcoholic steatohepatitis with Phyllanthus urinaria: a randomized trial. J Gastroenterol Hepatol. 2013 Jan;28(1):57-62. doi: 10.1111/j.1440-1746.2012.07286.x.

  PMID: 23034128 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 28, 2010
• First Posted: September 29, 2010
• Study Start: May 1, 2010
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: February 24, 2014

Record last verified: 2014-02

Locations

CN (1)