Methylene Blue Treatment of Chronic Hepatitis B Virus Infection: a Pilot Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Reduction >1 log10 in the starting HBsAg level and > 2 log10 in the starting HBV DNA PCR level
研究概览
简要总结
HBV infection is a global public health problem. It is estimated that there are more than 250 million HBV carriers worldwide, of whom approximately 600,000 die each year from HBV-related liver disease. Diagnosis and treatment depend on the stage of infection, the degree of liver inflammation, and the progression of fibrosis. Patients with HBeAg-positive or -negative hepatitis are usually treated with nucleos(-t)ide analogues. This treatment inhibits HBV reverse transcriptase and reduces viral replication, but does not affect HBsAg production. Treatment must be continued for life in most cases and is associated with high cumulative costs and the risk of development of resistance.
Recently, it has been shown that patients who show a decrease in their HBsAg levels are more likely to become HBsAg negative, seroconvert and be able to stop antiviral treatment, which is the ultimate goal of treatment, but unfortunately rarely achieved. Methylene blue (MB) has been shown to have an effect on HBsAg levels in vitro, making it a promising test for a new treatment for HBV.
This is an explorative pilot study, open label, dose-escalation, single center clinical trial on the efficacy of MB against HBV infection.
Primary objective is to assess the efficacy of incremental doses of MB against hepatitis B virus in patients with chronic hepatitis B assessed by the reduction of both the HBsAg and HBV DNA levels after 6 months of treatment and 6 months of follow-up.
Participant will be treated for 6 months with MB 100 mg capsules, and then followed up for a further 6 months. The initial dose of MB might be increased if the patient is a non-responder.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent
- •Age ≥ 18 and < 80 years
- •Microbiologically confirmed chronic Hepatitis B Virus infection (according to the old terminology "inactive HBV carrier")
- •HBsAg levels within 20-15'000 IU/ml measured at the at least twice at 6-18 months apart
- •HBV DNA PCR levels within 1'000-20'000 IU/ml measured at least twice at 6-18 months apart
- •Negative pregnancy test in women of child-bearing age
排除标准
- •Documented refusal to participate in the study
- •Known G-6-Phophatase deficiency
- •Treatment with a serotoninergic drug
- •Ongoing treatment with a nucleos(-t)ide treatment
- •Clinically relevant concomitant liver disease
- •GPT > 2xULN
- •Fibroscan of > 8.0 KPa obtained ≤ 12 months before Visit 0/Screening
- •HBeAg positivity
- •Anti HDV antibody positivity
- •Breastfeeding women
研究组 & 干预措施
Methylene Blue
Subjects will be initially treated with an initial dose of 200mg/day for 8 weeks at which point the investigators will assess the effect of the treatment.
Those patients that obtain a "complete response" will continue their treatment up to a total of 24 weeks with the same dose. Those who do not reach a "complete response" will be exposed to the next higher dose of 400mg/day for the following 8 weeks and the investigators will then again assess the effect of the treatment.
Those patients that obtain a "complete response" will continue their treatment up to a total of 24 weeks with the same dose. Those who do not reach a "complete response" will be exposed to the next higher dose of 600mg/day for the following 8 weeks and the investigators will then assess the effect of the treatment.
干预措施: Methylene Blue (Drug)
结局指标
主要结局
Reduction >1 log10 in the starting HBsAg level and > 2 log10 in the starting HBV DNA PCR level
时间窗: From enrollment to the end of treatment at 6 months
Primary endpoints have been created according to the levels of HBsAg and HBV DNA PCR. The main primary endpoint is the reduction \>1 log10 in the starting HBsAg level and \> 2 log10 in the starting HBV DNA PCR level after 6 months of treatment (complete response).
次要结局
- Adverse Events(From enrollment to the end of follow up period (12 months in total))
- Treatment adherence(From enrollment to the end of follow up period (12 months in total))