Short Term Effects of Ivacaftor in Non-G551D Cystic Fibrosis Patients
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Sweat Chloride Concentration
研究概览
简要总结
This is a study of the short-term effects of ivacaftor on sweat chloride concentration and lung function in cystic fibrosis (CF) patients who fall outside current FDA approval. This new, first of its kind drug is approved for use only in CF patients with the G551D mutation in whom it safely confers considerable benefits. However, it is highly likely that CF patients with many other mutations can benefit similarly from this drug, some of whom can be identified by phenotype or genotype.
We will enroll up to 30 CF subjects with clinical presentations in which there is one or more signs of residual CF channel function. The signs of residual function include: normal digestion, concentration of chloride in sweat between 55 and 85, or milder than expected CF disease in a CF patient with severe gene mutations. The primary outcome measure will be the difference in sweat chloride concentration measured in subjects on placebo and on ivacaftor. Secondary outcome measured will be lung function.
详细描述
Ivacaftor is a cystic fibrosis (CF)channel potentiator that is associated with decreased sweat chloride concentration, improved lung function, and improved weight gain. It is currently FDA approved for use only in CF patients with the G551D gating mutation. In vivo data suggest that ivacaftor may potentiate CF channels coded for by many other mutations associated with residual channel function, i.e., that some CF protein is present in the cell membrane of affected cells. This includes all of the 9 other known gating mutations, but ivacaftor also may be effective in CF patients with non-gating mutations, including some associated with severe phenotype. Based on results from previous studies, we hypothesize that non-G551D patients with signs of residual CF channel activity might respond favorably to treatment with ivacaftor. This includes patients with any of the non-G551D gating mutations, that are pancreatic sufficient, that have a sweat chloride concentration between 55 and 85 mmol, or that are much healthier than expected. Hence, select CF patients treated with ivacaftor as compared to placebo will have a decrease in sweat chloride concentration by greater than 20 mmol, improvement in FEV1, and weight gain. To test our hypothesis, we will conduct a prospective double-blinded placebo-controlled crossover clinical study comparing treatment with ivacaftor to placebo therapy (see details below). Our specific aims are:
Specific Aim 1: To demonstrate a decrease in sweat chloride concentration by greater than 20 mmol from baseline after 14 days of ivacaftor as compared to placebo.
Specific Aim 2: To demonstrate improvement in lung function measures from baseline after 14 days of Ivacaftor as compared to placebo.
Specific Aim 3:To demonstrate weight gain from baseline after 14 days of Ivacaftor as compared to placebo.
Study Design:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Screening
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Two mutations known to cause cystic fibrosis and a sweat chloride concentration greater than or equal to 55 mmol
- •Greater than or equal to 6 years of age
排除标准
- •Homozygous F508del with a sweat chloride greater than 85 mmol
- •Taking medication known to interact with ivacaftor and chooses not to discontinue that medication
- •Is pregnant or planning to become pregnant during the study period
- •Less than 6 years of age
研究组 & 干预措施
ivacaftor-placebo
The ivacaftor-placebo arm receives a 2 week course of ivacaftor 150 mg twice daily followed by a 2 week washout period followed by a 2 week placebo course.
干预措施: ivacaftor (Drug)
ivacaftor-placebo
The ivacaftor-placebo arm receives a 2 week course of ivacaftor 150 mg twice daily followed by a 2 week washout period followed by a 2 week placebo course.
干预措施: Placebo (Drug)
placebo-ivacaftor
The placebo-ivacaftor arm receives a 2 week placebo course followed by a 2 week washout period followed by a 2 week course of ivacaftor 150 mg twice daily.
干预措施: ivacaftor (Drug)
placebo-ivacaftor
The placebo-ivacaftor arm receives a 2 week placebo course followed by a 2 week washout period followed by a 2 week course of ivacaftor 150 mg twice daily.
干预措施: Placebo (Drug)
结局指标
主要结局
Sweat Chloride Concentration
时间窗: 14 +/- 2 days
Sweat chloride concentration measured by pilocarpine iontophoresis, a standard clinical laboratory technique. Sweat collection accomplished with the Wescor Macroduct system. Sweat chloride is measured at the start and end of each study period. There are two study periods during which subjects take either ivacaftor or placebo.
次要结局
- Multibreath Washout Testing(14 +/- 2 days)
- Spirometry(14 +/- 2 days)