Clinical trial NCT06887036: Methylene Blue Treatment of Chronic Hepatitis B Virus Infection
Official title: Methylene Blue Treatment of Chronic Hepatitis B Virus Infection: a Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic HBV Infection
Keywords: HBV
chronic HBV
Methylene Blue
MB
Lead sponsor: Fondazione Epatocentro Ticino
Sponsor class: OTHER
First posted: 2025-03-20
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Reduction >1 log10 in the starting HBsAg level and > 2 log10 in the starting HBV DNA PCR level
timeFrame: From enrollment to the end of treatment at 6 months
Secondary outcomes:
measure: Adverse Events
timeFrame: From enrollment to the end of follow up period (12 months in total)
measure: Treatment adherence
timeFrame: From enrollment to the end of follow up period (12 months in total)
Other outcomes:
Locations:
city: Lugano
country: Switzerland
facility: Epatocentro Ticino
state: Ticino
Study officials:
References: