A Pilot Study Evaluating Single, High-dose Pharmacokinetics/Pharmacodynamics of Vitamin D3 in CF
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- Area under the plasma concentration versus time curve (AUC)
研究概览
简要总结
Despite the extensive literature on adverse clinical outcomes associated with vitamin D deficiency, there are currently no proven treatment strategy that effectively achieves and maintains optimal serum vitamin D status in cystic fibrosis (CF) patients. For the treatment of vitamin D deficiency, CF Foundation currently recommends 2,000 IU daily. However, because achieving adequate serum 25(OH)D levels is a challenge in CF, higher doses of vitamin D may be necessary to reach and maintain vitamin D sufficiency. Poor oral bioavailability of ergocalciferol has been demonstrated in CF patients, which may potentially also be an issue with cholecalciferol. In order to optimize the treatment of vitamin D deficiency in CF, the kinetic disposition must be well understood. However, there are very few data currently available describing the kinetics of both vitamin D and 25-hydroxyvitamin D, and to the investigator's knowledge, no studies have yet characterized the pharmacokinetic disposition of vitamin D and its metabolites in cystic fibrosis. Addressing this issue is crucial in effectively and safely correcting vitamin D deficiency in CF.
详细描述
Clinically stable CF patients with a history of pancreatic insufficiency (n=6) and matching non-CF subjects (n=6) will be recruited in this study. All subjects will be pre-screened for 25(OH)D status to include those with 25(OH)D levels below 30 ng/mL. The subjects will receive a single oral dose (300,000 - 600,000 IU) of vitamin D3, and the dose will be based on study participant's baseline 25-hydroxyvitamin D3 level. For CF patients, the dose will be administered with food and pancreatic enzyme supplement. This dose was chosen as previous studies in pediatric CF patients demonstrated that a large single dose of up to 600,000 IU vitamin D3 raised and maintained sufficient 25(OH)D concentrations without any signs of adverse events.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- •For CF, diagnosis of CF based on positive sweat chloride or known CF mutation
- •For CF, Patients with pancreatic insufficiency
- •Age ≥ 18 years
- •Serum 25(OH)D concentrations below 30 ng/mL (75 nmol/L)
排除标准
- •Pregnancy
- •History of lung transplant,
- •Severe anemia (hemoglobin concentration < 7 g/dL),
- •Liver disease (AST/ALT > 3x ULN), kidney disease (GFR ≤ 40 mL/min), or granulomatous conditions
- •Patients taking steroids, cholesterol-lowering drug (cholestyramine), weight-loss drugs (orlistat) , statins, anti-tuberculosis drugs (rifampin and isoniazid), phenobarbital, phenytoin, carbamazepine, immunosuppressants (cyclosporine, tacrolimus)
结局指标
主要结局
Area under the plasma concentration versus time curve (AUC)
时间窗: 10 weeks
Peak plasma concentrations (Cmax)
时间窗: 10 weeks
Time taken to reach the maximum concentration (Tmax)
时间窗: 10 weeks
次要结局
- Levels of serum inflammatory biomarkers(10 weeks)
研究者
Paul Beringer
Professor of Clinical Pharmacy
University of Southern California