Tumor Necrosis Factor-α Induces Vitamin D Resistance in Small Intestinal Calcium Absorption
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Intestinal Absorption of Calcium
研究概览
简要总结
This study is a pilot study to determine whether patients with TNFα excess have decreased calcium absorption in response to calcitriol (1,25-dihydroxyvitamin D, the active form of vitamin D) compared to normal controls. This initial pilot study is being done to determine if it is feasible to conduct a study where TNFα could be blocked (e.g., by anti-TNFα therapy such as Enbrel® or Remicade®) to improve vitamin D dependant calcium absorption and thus bone health.
详细描述
Vitamin D is important for the maintenance of normal calcium homeostasis by improving the efficacy of calcium absorption from the small intestine. The efficacy of calcium absorption is decreased with aging, menopause, and other inflammatory states. Subjects who have low intestinal absorption of calcium are at risk for developing osteoporosis and fractures. Early data suggests that patients with rheumatoid arthritis (RA) and Crohn's disease appear to have decreased calcium absorption. Patients with RA and Crohn's disease have elevated levels of TNFα in local tissues and systemically which may be causing resistance to vitamin D dependant calcium absorption.
Recently a new vitamin D dependant calcium channel important for calcium absorption has been discovered in the small intestine called Transient Receptor Potential Vallinoid type 6 (TRPV6). We have some pre-clinical data in rats to suggest that TNFα has a role in inhibiting the expression of this protein by decreasing the induction of this protein in response to vitamin D treatment.
HYPOTHESIS:
Subjects with disease conditions that result in elevated TNFα have vitamin D resistance and inability to increase calcium absorption with increasing concentrations of calcitriol.
STUDY DESIGN:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Age 18 to 50
- •History of Crohn's disease or Rheumatoid Arthritis (cases) or healthy individuals (controls)
排除标准
- •Subjects already taking activated vitamin D medications such as calcitriol, Zemplar®, Hectoral®
- •Vitamin D deficiency defined as 25(OH)D ≤ 20 ng/ml
- •Post-menopausal women (absence of menses for greater than 6 months by history or FSH level >20)
- •History of nephrolithiasis
- •History of hypercalcemia or hypercalciuria
- •Short bowel disease
- •Glucocorticoid use
- •Use of osteoporosis medication (bisphosphonate, calcitonin or teriparatide)
- •Chronic kidney disease (calculated GFR <60 ml/min/1.73 m2)
- •History of hyperparathyroidism (PTH greater than upper limit of normal) or
- •Hypoparathyroidism (PTH below lower limit of normal)
研究组 & 干预措施
Calcitriol
Calcitriol 0.25 mcg orally twice a day for 7 days or calcitriol 0.50 mcg orally twice a day for 7 days.
干预措施: calcitriol (Drug)
结局指标
主要结局
Intestinal Absorption of Calcium
时间窗: 12 Weeks
Fractional Absorption of Calcium
时间窗: 7 week
Fractional absorption of calcium (see citation for complete details)
次要结局
未报告次要终点
研究者
Vin Tangpricha
Staff Physician
Atlanta VA Medical Center