Clinical trial NCT01754961: Effects of Vitamin D on Inflammation in Liver Disease
Official title: Effects of Vitamin D on Inflammation in Liver Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Hepatitis C Infection
Vitamin D Deficiency
Lead sponsor: Veterans Medical Research Foundation
Sponsor class: OTHER
First posted: 2012-12-21
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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by the presence of activated M1 macrophages in liver biopsies from patients with severe drug-induced liver injury (unpublished observations).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

Eligibility 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.

Primary outcomes:
measure: Macrophage activation
timeFrame: one week
Secondary outcomes:
measure: Liver injury
timeFrame: one week
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego, CTRI
state: California
Study officials:
affiliation: University of California, San Diego
name: Mario Chojkier, MD
role: PRINCIPAL_INVESTIGATOR
References: