About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Single group
Treatments tested in this trial
Methylene Blue
DrugSubjects 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.
Treatment groups
Trial outcomes
Primary outcomes
Reduction >1 log10 in the starting HBsAg level and > 2 log10 in the starting HBV DNA PCR level
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).
Secondary outcomes
Adverse Events
Adverse Events during both the 6 months treatment period and the 6 months follow-up period after the treatment
Treatment adherence
Assessment of treatment adherence, through IMP accountability
Sponsors and contacts
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