Effects of Vitamin D on Inflammation in Liver Disease

Vitamin D Deficiency Clinical Trial

Official title:

Effects of Vitamin D on Inflammation in Liver Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01754961
• Other study ID #: UCSD-111219
• Status: Recruiting
• Phase: Phase 2
• First received: November 17, 2011
• Last updated: December 18, 2012
• Start date: November 2011
• Est. completion date: January 2014

Study information

• Verified date: December 2012
• Source: Veterans Medical Research Foundation
• Contact: Kim Inocencio, BS
• Phone: 619-717-1906
• Email: kcinocencio[@]ucsd.edu
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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by the presence of activated M1 macrophages in liver biopsies from patients with severe drug-induced liver injury (unpublished observations).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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: January 2014
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Hepatitis C
• Hepatitis C Infection
• Liver Diseases
• Vitamin D Deficiency

Intervention

Drug:
• Vitamin D
Vitamin D 500,000 IU given orally on Day 1
• Placebo
Placebo given orally on Day 1

Locations

Country	Name	City	State
United States	UC San Diego, CTRI	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
Veterans Medical Research Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Macrophage activation	As determined by serum levels and macrophage cytokine production compared to placebo and baseline	one week	No
Secondary	Liver injury	Measurement of ALT/AST	one week	Yes