Effects of Vitamin D on Inflammation in Liver Disease
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Macrophage activation
研究概览
简要总结
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.
详细描述
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by the presence of activated M1 macrophages in liver biopsies from patients with severe drug-induced liver injury (unpublished observations).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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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.
研究组 & 干预措施
Placebo
Placebo will be given on Day 1 orally
干预措施: Placebo (Drug)
Vitamin D
Administration of 500,000 IU Vitamin D orally on Day 1
干预措施: Vitamin D (Drug)
结局指标
主要结局
Macrophage activation
时间窗: one week
As determined by serum levels and macrophage cytokine production compared to placebo and baseline
次要结局
- Liver injury(one week)
研究者
Mario Chojkier
Professor of Medicine
Veterans Medical Research Foundation