High-Dose Vitamin D and Antimicrobial Peptide Expression in Lung Failure
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 2
- 主要终点
- Number of Participants With Plasma 25(OH)D Concentration >30ng/mL at Baseline
研究概览
简要总结
The increasing rate of hospital-acquired infection and antibiotic resistance are major causes of prolonged ICU stay and death in hospitalized patients. The enormous impact of ICU-related infection demands the need for cost-effective therapies that can be rapidly implemented to improve patient immune response to control infection. Unfortunately, little high-quality comparative effectiveness research has been performed on micronutrient treatment regimens as methods to decrease hospital-acquired infection in critically ill patients. Critically ill medical and surgical patients have an extremely high prevalence of vitamin D insufficiency.
We will perform a rigorous, double-blind, randomized, controlled, pilot clinical trial in ventilator-dependent ICU patients to test the clinical/metabolic safety and efficacy of two doses of oral high-dose vitamin D3 therapy versus standard therapy (no supplemental vitamin D). The primary endpoint is to test whether high-dose regimens [either 50,000 or 100,000 international units (IU) of enteral vitamin D3 given daily for 5 consecutive days (total dose = 250,000 or 500,000 IU, respectively) increase plasma 25(OH)D concentrations into a desirable range (> 30 ng/mL).
详细描述
- We will evaluate, over 12 weeks, the safety and efficacy of two high-dose vitamin D3 regimens in severely ill ICU patients. Vitamin D or placebo ( depending on study arm) will be given sequentially in divided doses for 5 days
- We will explore whether these vitamin D regimens are capable of increasing the production of key antimicrobial peptides LL-37 and hBD-2 ( substances produced by our bodies to fight infections), in both the blood and in lung.
- We will determine whether a higher vitamin D level in the blood is associated with a decrease in hospital infection rates and other complications in high-risk ICU patients with respiratory failure.
Study Design:
Enrollment goal is 36 patients. Once consent is obtained subjects will be randomly assigned to one of three study groups. Each group consists of 12 patients with enteral access ; a placebo arm, an arm where subjects receive 50,000 IU of Vitamin D for 5 days, and a third arm where subjects receive 100,000 IU of Vitamin D for 5 days.
Methods: Baseline blood samples (25-hydroxyvitamin D, vitamin D binding protein, ionized calcium, LL-37,and hBD-2) will be taken on study day 7,14,21,28,84 days. On study day 1 and 8, LL-37, hBD-2, cathelicidin from BAL fluid will also be analyzed. Patients will be given either placebo, Vitamin D3 50,000 IU x 5 days (total 250,000 IU) or Vitamin D3 100,000 IU x 5 days (total 500,000 IU) with an intention to treat model. Baseline data on the patients including demographic, laboratory, documented infections, severity illness score (APACHE II) and organ dysfunction score (SOFA) will be collected. ELISA assay on the serum and BAL will be performed.
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
- Quadruple (Participant, Care Provider, 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
- •Receiving care in an intensive care unit (ICU)
- •Age greater than 18 years
- •Expected to require mechanical ventilation for at least 72 hours after entry
- •Expected to survive and remain in the ICU for at least 96 hours after study entry
- •To enable delivery of study drug, the subject has enteral access in place and is deemed able to tolerate enteral drug administration
排除标准
- •Inability to obtain or declined informed consent from the subject and/or legally authorized representative
- •Pregnancy
- •Ongoing shock
- •Current hypercalcemia (albumin-corrected serum calcium > 10.8 mg/dL or ionized calcium > 5.2 mg/dL)
- •History of therapy with high-dose vitamin D to treat vitamin D deficiency within previous 6 months
- •History of disorders associated with hypercalcemia; history of cancer with history of hypercalcemia within the past 1 year, hyperparathyroidism, sarcoidosis, nephrolithiasis]
- •Chronic renal dysfunction requiring chronic dialysis
- •Known history of cirrhosis
- •History of AIDS
- •The patient has received any investigational drug within 60 days prior to study entry.
研究组 & 干预措施
Inactive Substance
Arm where patients receive inactive substance for 5 days.
干预措施: Inactive substance (Other)
Enteral vitamin D3 50,000 IU
An arm where subjects receive 50,000 IU of Vitamin D for 5 days.
干预措施: Enteral Vitamin D3 50,000 IU (Drug)
Enteral Vitamin D3 100,000 IU
Arm where subjects receive 100,000 IU of Vitamin D for 5 days
干预措施: Enteral Vitamin D3 100,000IU (Drug)
结局指标
主要结局
Number of Participants With Plasma 25(OH)D Concentration >30ng/mL at Baseline
时间窗: Baseline
The number of participants with a plasma 25(OH)D concentration in the desirable range (defined as greater than 30 ng/mL) at the baseline measurement.
Number of Participants With Plasma 25(OH)D Concentration >30ng/mL at Day 28
时间窗: Day 28
The number of participants with a plasma 25(OH)D concentration in the desirable range (defined as greater than 30 ng/mL) at the Day 28 measurement.
Number of Participants With Plasma 25(OH)D Concentration >30ng/mL at Day 84
时间窗: Day 84
The number of participants with a plasma 25(OH)D concentration in the desirable range (defined as greater than 30 ng/mL) at the Day 84 measurement.
Number of Participants With Plasma 25(OH)D Concentration >30ng/mL at Day 7
时间窗: Day 7
The number of participants with a plasma 25(OH)D concentration in the desirable range (defined as greater than 30 ng/mL) at the Day 7 measurement.
Number of Participants With Plasma 25(OH)D Concentration >30ng/mL at Day 14
时间窗: Day 14
The number of participants with a plasma 25(OH)D concentration in the desirable range (defined as greater than 30 ng/mL) at the Day 14 measurement.
Number of Participants With Plasma 25(OH)D Concentration >30ng/mL at Day 21
时间窗: Day 21
The number of participants with a plasma 25(OH)D concentration in the desirable range (defined as greater than 30 ng/mL) at the Day 21 measurement.
次要结局
- Change in Plasma LL-37 Levels(Baseline, Day 7, Day 14)
- Duration of Time on Ventilator(12 weeks)
- Duration of Time in Intensive Care Unit (ICU)(12 weeks)
- Duration of Time in Hospital(12 weeks)
- Change in Sequential Organ Failure Assessment (SOFA) Score(Baseline, Day 7)
- Number of Hospital Acquired Infections(12 weeks)
- Number of Hospital Mortality Cases(12 weeks)
- Day 84 Mortality(Day 84)
研究者
Greg S. Martin, M.D., M.Sc.
Associate Professor
Emory University