Effects of Vitamin D on Inflammation in Liver Disease

Sponsor

Veterans Medical Research Foundation (Other)

Overall Status

Unknown status

CT.gov ID

NCT01754961

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

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by the presence of activated M1 macrophages in liver biopsies from patients with severe drug-induced liver injury (unpublished observations).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

Anticipated 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 :

Nov 1, 2011

Anticipated Primary Completion Date :

Oct 1, 2013

Anticipated Study Completion Date :

Jan 1, 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 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

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

Outcome Measures

Primary Outcome Measures

Macrophage activation [one week]
As determined by serum levels and macrophage cytokine production compared to placebo and baseline

Secondary Outcome Measures

Liver injury [one week]
Measurement of ALT/AST

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.