Effects of Vitamin D on Inflammation in Liver Disease

Study Overview
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Brief Summary
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Chronic liver diseases are associated with inflammation. The investigators postulate that Vitamin D may modulate inflammation. Thus the investigators will study the effect of Vitamin D replacement in patients with Hepatitis C infection and Vitamin D deficiency.

Detailed Description
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Vitamin D appears to be a critical signaling molecule for macrophages because is needed for activation and differentiation of monocytes/macrophages. From our Preliminary Studies( VA Merit Review Grant), we propose that Vitamin D deficiency may alter the 'pro-inflammatory' ('classically activated') M1 macrophages , characterized by i] high expression of NOS2, TNF-a, IL-1, IL-6, IL-8, TGF-a, CXCL10, and CCL19; and ii] minimal expression of arginase 1 and mannose R. The clinical relevance of these findings is suggested by the presence of activated M1 macrophages in liver biopsies from patients with severe drug-induced liver injury (unpublished observations). Prospective vitamin D supplementation studies with appropriate endpoints are needed to define the role of vitamin D on inflammation in patients with chronic liver diseases.

Official Title
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Effects of Vitamin D on Inflammation in Liver Disease

Conditions
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Hepatitis C Infection, Vitamin D Deficiency

Intervention / Treatment
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* Drug: Vitamin D
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women aged 18 or older Total 25-OH Vit D < 25 ng/mL Infection with HCV genotype 1 (subjects infected with multiple genotypes are not eligible). Plasma HCV RNA concentration of >100,000 IU/mL. HCV-infected subjects naïve to treatment: subjects who either have never been treated for HCV infection or who previously received HCV treatment ending > 3 months prior to enrollment (including, any IFN-Alpha with or without ribavirin, or other anti-HCV antiviral medication). Exclusion Criteria: Women who are pregnant or breastfeeding. Patients with Sarcoidosis, Histoplasmosis, Lymphoma, Primary Hyperparathyroidism or Idiophatic Hypercalcemia. Liver Cirrhosis. Known active gastrointestinal disease that could interfere with the absorption of the test article. Laboratory determinations at screening as follows: Hemoglobin <10 g/dL . Serum creatinine that is not within normal limits. However, such subjects may be enrolled if the Cockroft-Gault glomerular filtration rate (GFR) is > 50 mL/minute. Unstable hypertension, cardiac disease or type 2 diabetes requiring changes in treatment with medications 4 weeks prior to screening or during the screening period. Use of an investigational drug within 4 weeks before the screening visit or during the screening period. Use of systemic immunosuppressants (including systemic, oral, or intravenous corticosteroids) or immunomodulating agents within 4 weeks before the screening visit or during the screening period.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo will be given on Day 1 orally | Drug: Placebo<br>* Placebo given orally on Day 1<br>* Other names: Emulsion placebo;|
| Active Comparator: Vitamin D<br>Administration of 500,000 IU Vitamin D orally on Day 1 | Drug: Vitamin D<br>* Vitamin D 500,000 IU given orally on Day 1<br>* Other names: Vitamin D Drug;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Macrophage activation | As determined by serum levels and macrophage cytokine production compared to placebo and baseline | one week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver injury | Measurement of ALT/AST | one week |