Hepatitis C Infection, Vitamin D Deficiency
Conditions
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by the presence of activated M1 macrophages in liver biopsies from patients with severe drug-induced liver injury (unpublished observations).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.
Interventions
DRUGVitamin D
Vitamin D 500,000 IU given orally on Day 1
DRUGPlacebo
Placebo given orally on Day 1
Sponsors
Veterans Medical Research Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Macrophage activation | one week | As determined by serum levels and macrophage cytokine production compared to placebo and baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Liver injury | one week | Measurement of ALT/AST |
Countries
United States
Contacts
Primary ContactKim Inocencio, BS
Outcome results
None listed