Vitamin D Supplementation in Cirrhotic Patients
Condition: Cirrhosis; Vitamin D Deficiency
MeSH terms: Vitamin D Deficiency
Study type: Interventional
Phase: Phase 2

Summary: 
      Previous studies suggested that vitamin D deficiency is highly prevalent in cirrhotic
      patients and is related to the degree of liver dysfunction as well as mortality. In
      gastrointestinal disorders, vitamin D absorption can be highly reduced.

      We herein aim to investigate the efficacy of oral vitamin D supplementation in cirrhotic
      patients with vitamin D insufficiency.
    

Detailed description: 
      Cirrhosis of the liver is a slowly progressive disease with a high number of complications
      like hepatic encephalopathy, gastrointestinal bleeding, ascites, renal failure and
      hepatocellular cancer leading to death. Cirrhosis as a cause of death has increased
      progressively in the mortality data for the general population.

      This terminal liver disease as a complication of chronic viral hepatitis, alcoholism and
      metabolic disorders, with genetic and non-genetic predisposition, may be linked to
      nutritional aberration as a precursor to or an effect of the illness. Previous studies
      suggested that chronic liver diseases may be related to high prevalence of vitamin D
      deficiency and in gastrointestinal disorders the vitamin D absorption can be highly reduced.

      Patients with cirrhosis are often presented with malnutrition and one of the limiting factors
      of the intestinal malabsorption is the portal hypertension due to the liver disease. Beside
      nutrition the main source of vitamin D is sunlight and ultraviolet-B inducing the conversion
      of 7-dehydrocholesterol to vitamin D in the skin; therefore limited sunlight exposure of the
      skin may lead to an inadequate vitamin D status.

      Vitamin D itself is biologically inactive and has to be hydroxylated in the liver to
      25-hydroxyvitamin D (25(OH)D) as the main circulating metabolite used for classification of
      the vitamin D status. 1,25 hydroxyvitamin D (1,25(OH)D) is produced through conversion by the
      enzyme 1-alpha-hydroxylase in the kidney. This vitamin D metabolite shows a higher affinity
      for the vitamin D receptor (VDR) compared to 25(OH)D. After binding and activation of the VDR
      three percent of the human genome will be regulated. Among the main role of vitamin D
      metabolites to regulate calcium and bone homeostasis, they also show non-skeletal effects
      with relevance in the development of several chronic diseases. In this context, vitamin D
      deficiency has been associated with an increased risk of cancer , cardiovascular, autoimmune,
      and infectious diseases, Based on these findings, a significantly reduced risk of mortality
      was shown in patients with oral vitamin D supplementation in randomized controlled studies.

      Our previously published study presented a prospective association of vitamin D levels with
      occurrence of hepatic decompensation. Furthermore vitamin D deficiency was associated with
      high mortality in cirrhotic patients dependent on liver dysfunction. Concerning this aspect
      the main point is to investigate in this study whether low vitamin D status is the
      consequence of increasing deterioration of the liver synthesis or may even contribute to
      liver dysfunction. Low synthesis of vitamin D in the skin can be the result of reduced
      sunlight exposure and malnutrition and/or malabsorption in cirrhotic patients. On the other
      hand, organ dysfunction may impair the activity of 25-hydroxylase in the liver. Despite the
      above mentioned correlation between vitamin D deficiency and liver dysfunction there is still
      insufficient evidence to recommend oral vitamin D supplementation as a concomitant therapy in
      clinical practice because there exists no adequately designed randomized controlled trial
      that evaluates the necessary daily oral dose on vitamin D.

      We aim to address this issue in the present study so that the findings of our study will lead
      to implementation of treatment strategies for maintaining a sufficient vitamin D status in
      cirrhotic patients.
    

Intervention name(s): Vitamin D supplementation; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): oral administration of colecalciferol 2.800 IU once daily; oral administration of placebo (vehicle) once daily
Intervention MeSH terms: Vitamin D
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment