Effects of Vitamin D on Inflammation in Liver Disease

• ClinicalTrials.gov Identifier: NCT01754961
• Recruitment Status: Unknown
• First Posted: December 21, 2012
• Last Update Posted: December 21, 2012
• Sponsor: Veterans Medical Research Foundation
• Information provided by (Responsible Party): Mario Chojkier, Veterans Medical Research Foundation

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hepatitis C Infection; Vitamin D Deficiency	Drug: Vitamin D; Drug: Placebo	Phase 2

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by the presence of activated M1 macrophages in liver biopsies from patients with severe drug-induced liver injury (unpublished observations).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

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effects of Vitamin D on Inflammation in Liver Disease
• Study Start Date: November 2011
• Estimated Primary Completion Date: October 2013
• Estimated Study Completion Date: January 2014

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Placebo will be given on Day 1 orally	Drug: Placebo; Placebo given orally on Day 1; Other Name: 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 Name: Vitamin D Drug

Outcome Measures

Primary Outcome Measures :

1. Macrophage activation [ Time Frame: one week ]
   As determined by serum levels and macrophage cytokine production compared to placebo and baseline

Secondary Outcome Measures :

1. Liver injury [ Time Frame: one week ]
   Measurement of ALT/AST

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Kim Inocencio, BS; 619-717-1906; kcinocencio@ucsd.edu

Locations

United States, California

UC San Diego, CTRI; Recruiting

La Jolla, California, United States, 92093

Contact: Kim Inocencio, BS 619-717-1906 kcinocencio@ucsd.edu

Principal Investigator: Mario Chojkier, MD

Sponsors and Collaborators

Veterans Medical Research Foundation

Investigators

• Principal Investigator: Mario Chojkier, MD; University of California, San Diego

More Information

• Responsible Party: Mario Chojkier, Professor of Medicine, Veterans Medical Research Foundation
• ClinicalTrials.gov Identifier: NCT01754961
• Other Study ID Numbers: UCSD-111219
• First Posted: December 21, 2012
• Last Update Posted: December 21, 2012
• Last Verified: December 2012

Additional relevant MeSH terms:

Hepatitis C; Liver Diseases; Vitamin D Deficiency; Inflammation; Hepatitis; Digestive System Diseases; Pathologic Processes; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Vitamin D; Ergocalciferols; Vitamins; Micronutrients; Nutrients; Growth Substances; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents