Recruitment

Recruitment Status
Completed
Estimated Enrollment
60

Inclusion Criterias

25(OH)D levels below 30 ng/ml (measured at the baseline visit)
Negative pregnancy test in women of childbearing potential
Written informed consent
...
25(OH)D levels below 30 ng/ml (measured at the baseline visit)
Negative pregnancy test in women of childbearing potential
Written informed consent
Age between 18 and 75 years
Compensated and decompensated cirrhosis diagnosed by the hepatologist for at last three months prior to study start

Exclusion Criterias

Glomerular filtration rate (GFR) < 15 ml/min/1.73m²
Any disease with an estimated life expectancy below 1 year
Regular intake of more than 800 International Units (IU) of vitamin D during the last 4 weeks before study entry
...
Glomerular filtration rate (GFR) < 15 ml/min/1.73m²
Any disease with an estimated life expectancy below 1 year
Regular intake of more than 800 International Units (IU) of vitamin D during the last 4 weeks before study entry
Drug intake as part of another clinical study
Pregnancy or lactating women
Hypercalcemia defined as total serum calcium >2.65 mmol/L
Any clinically significant acute disease requiring drug treatment
Anticipated chemotherapy or radiation therapy during the study

Summary

Conditions
  • Cirrhosis
  • Vitamin D Deficiency
Type
Interventional
Phase
Phase 2
Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Masking: Double (Participant, Investigator)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 75 years
Gender
Both males and females

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 th...

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.

Inclusion Criterias

25(OH)D levels below 30 ng/ml (measured at the baseline visit)
Negative pregnancy test in women of childbearing potential
Written informed consent
...
25(OH)D levels below 30 ng/ml (measured at the baseline visit)
Negative pregnancy test in women of childbearing potential
Written informed consent
Age between 18 and 75 years
Compensated and decompensated cirrhosis diagnosed by the hepatologist for at last three months prior to study start

Exclusion Criterias

Glomerular filtration rate (GFR) < 15 ml/min/1.73m²
Any disease with an estimated life expectancy below 1 year
Regular intake of more than 800 International Units (IU) of vitamin D during the last 4 weeks before study entry
...
Glomerular filtration rate (GFR) < 15 ml/min/1.73m²
Any disease with an estimated life expectancy below 1 year
Regular intake of more than 800 International Units (IU) of vitamin D during the last 4 weeks before study entry
Drug intake as part of another clinical study
Pregnancy or lactating women
Hypercalcemia defined as total serum calcium >2.65 mmol/L
Any clinically significant acute disease requiring drug treatment
Anticipated chemotherapy or radiation therapy during the study

Locations

Gratwein, Styria, 8112
Graz, Styria, 8036
Gratwein, Styria, 8112
Graz, Styria, 8036

Tracking Information

NCT #
NCT02009748
Collaborators
Not Provided
Investigators
  • Principal Investigator: Rudolf E Stauber, MD Dept of Internal Medicine, Medical University of Graz
  • Rudolf E Stauber, MD Dept of Internal Medicine, Medical University of Graz