Effects of Vitamin D on Inflammation in Liver Disease

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.

Study Overview

• Status: Unknown
• Conditions: Vitamin D Deficiency; Hepatitis C Infection
• Intervention / Treatment: Drug: Placebo; Drug: Vitamin D

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by the presence of activated M1 macrophages in liver biopsies from patients with severe drug-induced liver injury (unpublished observations).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 Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • Recruiting
      • UC San Diego, CTRI
      • Contact: Kim Inocencio, BS; Phone Number: 619-717-1906; Email: kcinocencio@ucsd.edu
      • Principal Investigator: Mario Chojkier, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Placebo will be given on Day 1 orally	Drug: Placebo; Placebo given orally on Day 1; Other Names: Emulsion placebo
ACTIVE_COMPARATOR: Vitamin D; Administration of 500,000 IU Vitamin D orally on Day 1	Drug: Vitamin D; Vitamin D 500,000 IU given orally on Day 1; Other Names: Vitamin D Drug

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Veterans Medical Research Foundation
• Investigators: Principal Investigator: Mario Chojkier, MD, University of California, San Diego

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (ANTICIPATED): October 1, 2013
• Study Completion (ANTICIPATED): January 1, 2014

Study Registration Dates

• First Submitted: November 17, 2011
• First Submitted That Met QC Criteria: December 18, 2012
• First Posted (ESTIMATE): December 21, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): December 21, 2012
• Last Update Submitted That Met QC Criteria: December 18, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Nutrition Disorders; Flaviviridae Infections; Hepatitis, Viral, Human; Avitaminosis; Deficiency Diseases; Malnutrition; Hepatitis; Liver Diseases; Inflammation; Hepatitis C; Vitamin D Deficiency; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: UCSD-111219