Zinc Homeostasis and Kinetics in Children With CF
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Zinc balance
研究概览
简要总结
Zinc deficiency has occasionally been reported in CF, but the need for additional zinc is unclear. We will examine the effect of additional zinc supplements on zinc absorption, zinc excretion, zinc balance and zinc kinetics in children with CF. Twelve children with CF will receive additional zinc, and twelve will not. We will also compare the children with CF to 12 healthy children without CF. We hypothesize that children with CF will have poor zinc absorption and high zinc excretion, leading to poor zinc balance and abnormal zinc kinetics. We hypothesize that those children with CF who are given zinc supplements will have higher zinc balance and more normal zinc kinetics than those without supplementation, and that zinc balance and zinc kinetics will be similar to healthy children.
详细描述
Overt zinc deficiency presents with features of acrodermatitis enteropathica (AE) including diarrhea, dermatitis, growth failure, and poor immune function. AE has been described as a complication of cystic fibrosis, and can be the initial presenting feature. As AE has almost never been described in otherwise healthy subjects consuming self-selected diets, this suggests a profound disturbance in zinc metabolism, either in absorption or excretion, can occur in CF.
Few studies have measured zinc absorption in children with CF. Those that have had demonstrated significant reductions in zinc absorption in CF subjects with pancreatic insufficiency with a significant increase in zinc absorption with pancreatic enzyme replacement. However, zinc metabolism is maintained by changes in fractional zinc absorption and zinc losses in to the gastro-intestinal tract (endogenous fecal zinc excretion). Of these two mechanisms, changes in endogenous fecal zinc excretion appear to be the more important. To date, only one study has measured endogenous fecal zinc excretion in subjects with CF. Krebs et al. studied 15 infants, less than 4 months of age, newly diagnosed with CF. They found that all infants were in negative zinc balance, and that endogenous fecal zinc excretion was significantly correlated with the degree of fat malabsorption. These results are difficult to interpret as there was no control group studied, and there is little published data on zinc absorption in healthy infants of this age, and no data on endogenous fecal zinc excretion.
Clearly, a better measure of zinc status is required to fully understand the importance of zinc deficiency in CF, and the relationship between fat malabsorption and zinc balance. In the past, we have used novel stable isotope-based multicompartmental models to study zinc status in healthy and disease states. These have proved able to detect changes in zinc metabolism in two experimental paradigms of zinc deficiency, even before the plasma zinc becomes abnormal.
We hypothesize that,
- Children with CF will have worse zinc status, lower fractional zinc absorption, increased endogenous fecal zinc excretion, and poorer zinc balance, than age-matched controls.
- In children with CF, endogenous fecal zinc excretion will be significantly positively correlated, and zinc absorption and zinc balance significantly negatively correlated with fecal fat excretion.
- After two months of zinc supplementation with 20 mg/d zinc as zinc acetate, children with CF will have similar zinc status, fractional zinc absorption, endogenous fecal zinc excretion, and zinc balance as age-matched controls.
- Two months of zinc supplementation will not affect iron status (Hemoglobin, serum ferritin, serum transferrin receptors) or copper status (serum copper, ceruloplasmin, copper/ zinc superoxide dismutase).
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
- 8 Years 至 14 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged 8-14 years old
- •Have clinical pancreatic insufficiency (defined as the need for pancreatic enzyme replacement)
- •Have no other medical problems except CF (and its complications)
- •Weigh > 25kg
排除标准
- •Are taking any medicines (other than for CF and its complications)
- •Have known pancreatic endocrine dysfunction
- •Are taking more than 10 mg/d elemental zinc supplements
- •Have had major GI surgery, including gut resection, but not including surgery for decompression of meconium ileus (if this was the presenting feature of CF)
研究组 & 干预措施
1
CF, Zinc acetate
干预措施: Zinc acetate (20mg/d) (Drug)
2
CF, Placebo
干预措施: Zinc acetate (20mg/d) (Drug)
结局指标
主要结局
Zinc balance
时间窗: 120h
次要结局
- Serum ceruloplasmin(8wk)
- Serum copper(8wk)
- Serum ferritin(8wk)