Can Vitamin D Supplementation Improve Hepatitis C Cure Rates
Condition: Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis
Study type: Interventional
Phase: Phase 3

Summary: 
      Evidence suggests that vitamin D may be directly or indirectly a co-factor for the efficacy
      of Hepatitis C virus, (HCV), antiviral therapies. The level of vitamin D necessary for
      optimum immune function is ill defined and many of those with HCV infection in Scotland are
      below these levels. Vitamin D is a cheap and safe medication, so its addition to anti-viral
      therapy should be highly cost-effective even if only a modest increase in SVR was achieved.
      Given the Scottish HCV epidemic, the world leading government response to it and the
      nationally low vitamin D levels, Scotland is perfectly placed to answer this question.
      Therefore the investigators hypothesize that vitamin D supplementation will improve SVR and
      propose a randomised controlled trial to test this hypothesis. The anticipated end of study
      date for this study is April 2015
    

Detailed description: 
      Hepatitis C is a major health problem for Scotland with greater than 1% of the population
      infected; the Scottish Government has recognised this and mounted the Hepatitis C action
      plan, recognised as the world leading public health response to the epidemic. The key aim of
      this is to expand treatment access and numbers of patients cured of HCV infection to prevent
      patients developing the complications of cirrhosis and hepatocellular carcinoma.

      The success of treatment for HCV depends on genotype and is measured by the Sustained Viral
      Response (SVR). The SVR is the absence of virus 24 weeks after end of treatment and has been
      shown to be a cure of infection. The FDA has recently suggested SVR can be assessed at 12
      weeks, in clinical trials. Scotland has an equal mix of genotype 1 & 3 HCV infection
      accounting for greater than 95% of those infected. Treatment involves Pegylated Interferon
      injections weekly and Ribavirin twice daily for 6 months for HCV genotype 3 infection, with
      an SVR of 70%. For genotype 1 infection treatment is with the above dual therapy with the
      addition of a protease inhibitor, for treatment duration of 6-12 months leading to SVR rates
      of 65-70%. There are an increasing number of new pharmacological products in advanced
      development that will be available for clinicians to use but these, as well as increasing
      efficacy, will increase cost. So it requires clinicians to make treatment as effective as
      possible.

      Vitamin D has traditionally been associated with bone health, with definite deficiency
      causing osteomalacia and making a contribution to osteoporosis. The traditional, currently
      used normal ranges for Vitamin D are based on prevention of bone diseases. Recently and
      controversially it has been suggested that low normal levels of vitamin D are associated with
      multiple other disease states, including cancer, infection and cardiovascular disease
      Additionally it has been suggested that many of the normal population in Scotland are vitamin
      D deficient. Other studies have shown that drug users, a high risk group for HCV infection
      have similarly deficient levels of vitamin D. Studies have suggested that up to 92% of those
      with chronic liver disease have vitamin D levels below that deemed acceptable physiologically
      to maintain health.

      Some data is now available to support the role of vitamin D supplementation in the treatment
      of hepatitis C and improving SVR rates. Several observational studies have found an
      association between low vitamin D levels and reduced SVR rates, and additionally one study
      has shown an association between a single nucleotide polymorphism (SNP) in vitamin D binding
      protein and treatment response. A small Israeli trial of vitamin D supplementation in HCV
      treatment has shown increased SVRs in those supplemented, but the study had a number of flaws
      including a failure of randomisation(13). Additionally there have been an abstract and a
      letter report of improved outcome with a vitamin D intervention . Biological mechanisms of
      interaction between vitamin D and the immune system have been explored. It has been shown
      that Vitamin D plays a role in the regulation of innate immunity, macrophage function, and
      cell mediated immunity Vitamin D receptors (VDR) are also expressed on many effector cells of
      the immune system; activated T and B cells, macrophages and monocytes which act to increase
      to enhance phagocytic action and interferon activity , it has also been suggested vitamin D
      has a direct effect on HCV. These give a biological basis for the effect of vitamin D on the
      success of antiviral therapy.

      A randomised controlled trial, to be successful, requires recruitment and retention of
      subjects in the trial. HCV infection is associated with chaotic lifestyles which might impair
      the rate of recruitment and retention, although the Scottish HCV clinical database audit
      clearly shows that, with all comers, routine HCV care in Scotland matches the results from
      the randomised clinical trials. This pilot study will also help determine the recruitment and
      retention rates for a larger trial in this population.
    

Intervention name(s): Active Comparator: Vigantol Oil (Vitamin D3); Mygliol Oil
Intervention type(s): Drug; Drug
Intervention description(s): Vitamin D Oral oil 100.000iu in 5 mls; Matched placebo comparator
Intervention MeSH terms: Vitamin D; Cholecalciferol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment