Vitamin D Supplementation in Cirrhotic Patients

Vitamin D Deficiency Clinical Trial

Official title:

Vitamin D Supplementation in Cirrhotic Patients: A Randomized, Multi-center, Double-blind, Placebo Controlled Trial to Evaluate Vitamin D Supplementation on Serum 25-hydroxyvitamin D Levels in Cirrhotic Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02009748
• Other study ID #: VITDZIRR
• Status: Completed
• Phase: Phase 2
• First received: December 9, 2013
• Last updated: June 3, 2015
• Start date: December 2013
• Est. completion date: June 2015

Study information

• Verified date: June 2015
• Source: Medical University of Graz
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Office for Safety in Health Care
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: June 2015
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 25(OH)D levels below 30 ng/ml (measured at the baseline visit)

• Compensated and decompensated cirrhosis diagnosed by the hepatologist for at last three months prior to study start

• Age between 18 and 75 years

• Written informed consent

• Negative pregnancy test in women of childbearing potential

Exclusion Criteria:

• Hypercalcemia defined as total serum calcium >2.65 mmol/L

• Pregnancy or lactating women

• Drug intake as part of another clinical study

• Glomerular filtration rate (GFR) < 15 ml/min/1.73m²

• Any disease with an estimated life expectancy below 1 year

• Any clinically significant acute disease requiring drug treatment

• Anticipated chemotherapy or radiation therapy during the study

• Regular intake of more than 800 International Units (IU) of vitamin D during the last 4 weeks before study entry

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cirrhosis
• Vitamin D Deficiency

Intervention

Dietary Supplement:
• Vitamin D supplementation
oral administration of colecalciferol 2.800 IU once daily
• Placebo
oral administration of placebo (vehicle) once daily

Locations

Country	Name	City	State
Austria	Department of Internal Medicine, LKH Hoergas	Gratwein	Styria
Austria	Department of Internal Medicine, Medical University of Graz	Graz	Styria

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Graz

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	serum 25(OH)D		8 weeks after study start	No
Secondary	Liver function tests	Albumin, prothrombin time, bilirubin	8 weeks after study start	No
Secondary	Hyaluronic acid		8 weeks after study start	No