Evaluation of 4-Methylumbelliferone for Treatment of Chronic Hepatitis B (HBV) and Chronic Hepatitis C (HCV)
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Reduction of virus in blood to undetectable levels;
研究概览
简要总结
Open-label studies, anecdotal reports, and in vitro scientific research indicate that 4-methylumbelliferone (active ingredient of the dietary supplement Heparvit®) may prevent and reverse the symptoms and complications of chronic infection with hepatitis B virus (HBV)and hepatitis C virus (HCV). This effect has been observed among naïve patients as well as those who are non-responders to interferon, commonly used as first-line therapy for HBV and HCV. In order to scientifically address the efficacy of this 4-methylumbelliferone on chronic viral hepatitis, a randomized, placebo-controlled, blinded study is needed.
It is hypothesized that 4-methylumbelliferone may reduce the impact and aggressiveness of HBV and HCV upon the liver, thereby slowing the progression to potentially life threatening liver diseases such as cancer and cirrhosis. This is a preliminary study designed to determine any indications under controlled conditions that may warrant further detailed clinical studies.
详细描述
(i). Chronic hepatitis B
Chronicity of HBV following acute infection is strongly age-related; the majority (90%) of infants acquiring HBV perinatally go on to develop chronic infection, while most persons who acquire HBV later in life resolve their infection [ref 1]. Patients with chronic HBV have a 15-25% lifetime risk of liver cirrhosis and hepatic cancer. An estimated 5,000 people die each year from complications of chronic HBV infection (cirrhosis and hepatocellular carcinoma).
Three drugs have been approved by the Food and Drug Administration (FDA) for treatment of chronic HBV: interferon-α (IFN-α), lamivudine, and adefovir dipivoxil. Only one-third of chronic HBV patients develop a sustained response to IFN-α treatment, and adverse effects are common [ref 2]. Use of the newer orally-administered nucleoside analogues (lamivudine or adefovir dipivoxil) typically causes rapid initial clearance of virus and is associated with fewer adverse effects; however, seroconversion rates are low, and long-term therapy with lamivudine (required for sustained responses) frequently results in resistance [ref 2]. Adefovir dipivoxil has, so far, not shown the high rate of resistance observed with lamivudine, but it is expected that resistance will eventually develop [ref 3]. In summary, major problems with currently approved therapy of HBV include expense, toxicity, and development of resistance.
(ii). Chronic hepatitis C
Chronic viral hepatitis due to hepatitis C is an enormous medical problem, affecting approximately 170 million people worldwide (WHO) [ref 4]. In the U.S., an estimated 2.7 million people suffer from chronic HCV, with 10,000-12,000 deaths per year attributable to the disease (ref 5). Chronic HCV infections in the U.S. are usually acquired through injectable drug use, sexual contact, or receipt of contaminated blood products (before antibody screening was initiated in 1990). Most persons exposed to HCV (75%) develop asymptomatic chronic infection. Eventually, 15%-20% will die of cirrhosis and liver cancer without intervention [ref 4].
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Double
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Serum ALT at least 1.5x the upper limit of normal
- •For chronic HBV: Known positive serum HBeAg for at least 6 months; Presence of HBV DNA in serum
- •For chronic HCV: Presence of anti-HCV in serum within 6 months of enrollment; Positive serum HCV RNA (enrollment)
- •Written informed consent
排除标准
- •Treatment (within past 3 months) with interferon, ribavirin, lamivudine, entecavir, or adefovir dipivoxil
- •Current treatment with any drug or dietary supplement that could affect serum transaminase values (e.g., milk thistle)
- •Pregnancy or inability to practice contraception in patients capable of bearing or fathering children
- •Decompensated liver disease (as indicated by total bilirubin >4 mg/dL; albumin <3 g/dL; prolonged (>2 sec over control) prothrombin time; or history of bleeding esophageal varices, ascites or hepatic encephalopathy)
- •Active alcohol use, drug abuse, and/or psychiatric problems that, in the investigator's opinion, could interfere with participation in the study
- •Hepatitis D infection (for HBV-infected patients)
结局指标
主要结局
Reduction of virus in blood to undetectable levels;
Normalization of serum ALT and AST.
次要结局
- Reduced viral loads; Improvement of serum ALT and AST;
- Improvement in general health status;
- Improvement in serum marker of hepatic fibrosis;
- Loss of HBeAg/seroconversion to HBeAb (for HBV patients).