Effects of Vitamin D on Inflammation in Liver Disease

Phase 2

• Conditions: Hepatitis C Infection; Vitamin D Deficiency
• Interventions: Drug: Placebo; Drug: Vitamin D

• Registration Number: NCT01754961
• Lead Sponsor: Veterans Medical Research Foundation

Brief Summary

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

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by the presence of activated M1 macrophages in liver biopsies from patients with severe drug-induced liver injury (unpublished observations).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.

Study Timeline

• Study Start: 2011-11
• Study First Submitted: 2011-11-17
• Status Verified: 2012-12
• Study First Submitted QC: 2012-12-18
• Last Update Submitted: 2012-12-18
• Study First Posted: 2012-12-21
• Last Update Posted: 2012-12-21
• Primary Completion: 2013-10
• Study Completion: 2014-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 24

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo will be given on Day 1 orally
Vitamin D	Vitamin D	Administration of 500,000 IU Vitamin D orally on Day 1

Primary Outcome Measures

Name	Time	Method
Macrophage activation	one week	As determined by serum levels and macrophage cytokine production compared to placebo and baseline

Secondary Outcome Measures

Name	Time	Method
Liver injury	one week	Measurement of ALT/AST

Trial Locations

Locations (1)

UC San Diego, CTRI; 🇺🇸 La Jolla, California, United States