Influence of Cystic Fibrosis on Vascular Endothelial Function at Rest and During Exercise
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Percentage Flow-Mediated Dilation (FMD)
研究概览
简要总结
Perhaps one of the most disturbing aspects of Cystic Fibrosis (CF) is the associated premature death. Oxidative stress has been observed in patients with CF and exercise intolerance has been shown to predict mortality in patients with CF, regardless of how healthy their lungs are. A critical barrier to improving the quality of life and longevity in patients with CF is our lack of knowledge regarding the different reasons why patients with CF cannot exercise to the level of their peers. We have collected preliminary data to support our central hypothesis that oxidative stress contributes to the impairment in blood vessel function at rest and during exercise which ultimately oxygen transport and delivery resulting in exercise intolerance. Exercise is therapeutic medicine for patients with CF and this investigation represents a major breakthrough in the approach to begin understanding the physiological mechanisms which contribute to exercise intolerance in these patients.
详细描述
The overall goals of this proposal are to provide mechanistic evidence that oxidative stress contributes to 1) endothelial dysfunction and 2) exercise intolerance in patients with CF. This study consists of two separate sub-studies, or protocols. Protocol 1: AOC tested the effect of an antioxidant cocktail (AOC) on endothelial function at rest and during exercise in CF patients. Protocol 2: BH4 tested the effect of tetrahydrobiopterin (BH4) on endothelial function at rest and during exercise in CF patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 7 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Diagnosis of CF and healthy controls
- •Men and women (> 18 yrs. old)
- •Boys and girls (7 -17 yrs. old)
- •FEV1 percent predicted > 30%
- •Resting oxygen saturation (room air) >90%
- •Patients with or without CFRD
- •Traditional CF-treatment medications
- •Ability to perform reliable/reproducible PFTs
- •Clinically stable for 2 weeks (no exacerbations or need for antibiotic treatment within 2 weeks of testing or major change in medical status)
排除标准
- •Children 6 yrs. old and younger
- •FEV1 percent predicted < 30%
- •Resting oxygen saturation (room air) < 90%
- •Clinical diagnosis of heart disease
- •Pulmonary artery hypertension
- •Febrile illness within two weeks of visit
- •Current smokers
- •Currently pregnant or nursing
- •Individuals on vaso-active medications (i.e. nitrates, beta blockers, ACE inhibitors, etc.)
- •Inability to swallow pills
- •Patients with B. Cepacia (only ~3% of our CF center patient population)
研究组 & 干预措施
Protocol 1: AOC
measurements at baseline and 2 hours following the antioxidant cocktail that is comprised of over the counter vitamins (vitamin C 1000mg, vitamin E 600 IU, and alpha lipoic acid 600 mg) that will be given in two doses, 30 minutes apart.
干预措施: Antioxidant Cocktail (Dietary Supplement)
Protocol 2: BH4 (5mg)
measurements at baseline and 3 hours following the single dose of 5mg/kg Kuvan® or sapropterin dihydrochloride which is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4).BH4 has been shown in past studies to increase NO bioavailability.
干预措施: BH4 5mg (Drug)
Protocol 2: BH4 (20mg)
measurements at baseline and 3 hours following the single dose of 20mg/kg Kuvan® or sapropterin dihydrochloride which is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4).BH4 has been shown in past studies to increase NO bioavailability.
干预措施: BH4 20mg (Drug)
结局指标
主要结局
Percentage Flow-Mediated Dilation (FMD)
时间窗: pre-treatment Baseline and 2-3 hours post-treatment
Brachial artery FMD induced by reactive hyperemia assessed vascular endothelial function at baseline and several hours after treatment.
次要结局
未报告次要终点
研究者
Ryan Harris
Principal Investigator
Augusta University