A Pilot Study of Vitamin D in Boys With X-linked Adrenoleukodystrophy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 2
- 主要终点
- Percent of patients with a plasma 25-OH vitamin D level in the target range (40-80ng/ml) at 6 months
研究概览
简要总结
In this pilot study, the investigators will assess the safety of two high-dose regimens of oral vitamin D supplementation and measure the effects of vitamin D supplementation on markers of oxidative stress and inflammation in the blood and brain of study participants before, during, and after taking vitamin D supplements.
The goal of the study is to establish research measures (i.e. biomarkers) and an optimal dose for vitamin D supplementation in boys with the X-linked adrenoleukodystrophy (ALD) genotype.
详细描述
Prior research suggests that higher vitamin D levels in the blood are associated with reduced brain inflammation among individuals with multiple sclerosis, a disease that is similar to the cerebral demyelinating form of ALD. However, serious side effects (e.g. hypercalcemia, kidney stones) can occur if vitamin D levels get too high.
The current study is designed to establish a safe dose of vitamin D for boys with ALD. Although the doses chosen for this study are expected to be safe, the investigators will monitor participants for early signs of vitamin D-related toxicity. The investigators will also examine whether or not vitamin D supplementation affects markers of oxidative stress and inflammation in the blood and brains of ALD boys.
The study requires participants to agree to at least one year of participation. Participants will be asked to take a vitamin D supplement every day, submit blood for analysis every 3 months in the first year, and visit their study center (Stanford University or the Kennedy Krieger Institute) every 6 months throughout the period of study.
Participants will be assigned a vitamin D dose based on bodyweight at entry. Starting doses will include 1,000 or 2,000 international units (IU) of vitamin D3 daily for a 6 month period, followed by a conditional increase to 2,000, 3,000, or 4,000 IU daily thereafter if vitamin D levels have not achieved a target threshold. The vitamin D supplements will be provided by the study. In keeping with the current standard of care for ALD boys aged 18mos - 25 years, participants will need to visit the study site every six months in order to complete a clinic visit and MRI of the brain with gadolinium. As part of this study, however, participants' will need to submit blood work every 3 months during the first year in order for the study investigators to ensure that the participants' calcium and vitamin D levels are in a safe range and to study the effects of vitamin D on markers in the blood. The MRI protocol during the first year will also include one additional sequence (magnetic resonance spectroscopy) in order to measure brain metabolites.
The data generated from this study are intended, in part, to help design a future, large-scale clinical trial to determine whether vitamin D supplementation is capable of reducing the risk of developing the cerebral demyelinating form of ALD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Months 至 25 Years（Child, Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •history of liver or kidney disease
- •history of nephrolithiasis
- •history of hyperthyroidism
- •history of ulcerative colitis, Crohn's disease, celiac disease
- •taking medication interfering with gastrointestinal absorption
- •contraindication or inability to complete MRI every 6 months
结局指标
主要结局
Percent of patients with a plasma 25-OH vitamin D level in the target range (40-80ng/ml) at 6 months
时间窗: Plasma 25-OH vitamin D will be measured at 6 months
The investigators expect that 80% of patients will be in the target range 6 months (i.e. oral dose of 2000 IU daily)
Percent of patients with a plasma 25-OH vitamin D level in the target range (40-80ng/ml) at 12 months
时间窗: Plasma 25-OH vitamin D will be measured at 12 months
The investigators expect 100% of patients will be in the target range at 12 months (i.e. oral dose of 4000 IU daily)
次要结局
- Change in plasma macrophage inflammatory protein-1b levels(Measurements at baseline and 12 months)
- Change in protein carbonyl levels in whole blood at baseline and 12 months.(Measurements at baseline and 12months)
- Occurrence of serious adverse events(Measurements will be obtained at baseline, 3months, 6months, 9months, 12months)
- Change in glutathione (GSH) levels in brain(Measurements will be obtained at baseline, 6months, and 12months)
- Change in plasma interleukin-8 levels(Measurements a baseline and 12 months)
- Correlation between appearance of gadolinium enhancing brain lesion on MRI and most recent plasma 25-OH vitamin D level(Brain MRI at baseline, 6, 12, 18, 24, 30, and 36 months study enrollment. Plasma 25-OH vitamin D levels at baseline, 3, 6, 9, 12, 18, 24, 30, 36 months of enrollment.)
- Correlation between plasma 25-OH vitamin D and intracellular glutathione levels in peripheral monocytes(Measurements at baseline and 12 months)
- Change in glutathione (GSH) levels in blood(Measurements will be obtained at baseline, 6months, and 12months)
- Change in plasma monocyte chemoattractant protein-1 levels(Measurements at baseline and 12 months)
研究者
Keith Van Haren
Assistant Professor
Stanford University