Supplementation of Oral Reduced Glutathione in Pediatric Cystic Fibrosis for Growth Failure
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- Clark Bishop
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Weight Percentile at 3 Months
研究概览
简要总结
Many individuals with cystic fibrosis experience growth failure. The reasons are not clear, but inflammation of the gut in these patients seems to be one important reason. Glutathione is important to normal function of the intestine and lungs. Glutathione functions to decrease inflammation and to thin mucus. However, in cystic fibrosis, glutathione gets trapped inside of cells, so it cannot travel to the surface of the cells and perform its proper function. Moreover, glutathione has been shown to improve nutritional status in patients with AIDS and cancer.
Investigators hypothesize that supplementation of oral glutathione to pediatric individuals with cystic fibrosis could improve growth failure.
详细描述
Cystic fibrosis (CF) is known principally for its pulmonary consequences. However, for most individuals with CF, the earliest manifestations are not pulmonary, but gastro-intestinal. Many children experience growth failure. Chronic gut inflammation also develops. Research has also established that lung function scores are significantly correlated with Body Mass Index (BMI) and weight percentile in CF. Therefore, interventions to improve the gastro-intestinal dimension of CF in early childhood have the potential to ameliorate the course of the disease over the life span of the patient. Both Cochrane Database reviews and a recent review commissioned by the Cystic Fibrosis Foundation found only fair evidence for current nutritional guidelines.Therefore, there is a pressing need for a treatment for CF growth failure that is more effective and less invasive than current treatments.
The discovery that CF is associated with significantly diminished efflux of reduced glutathione (GSH) from most cells in the body offers a new perspective on the pathophysiology of this disease. GSH plays several important roles; among the most important are the following: 1) primary water-soluble antioxidant; 2) mucolytic capable of cleaving disulfide bonds; and 3) regulator of immune system function. The relationship between redox ratio (GSH:GSSG) and total glutathione (GSH+GSSG) and the initiation of inflammation is well established in the research literature.
GSH is also an important component of the epithelial lining fluid of the intestines, helping to keep intestinal mucus thin, serving to defend the intestinal system against reactive oxygen species, and keeping inflammation in check under normal circumstances. GSH is an FDA-approved treatment for AIDS-related cachexia. The growing recognition of GSH system dysfunction in CF, coupled with an established research literature on the role of GSH in gastro-intestinal function and weight gain in non-CF contexts, suggest a new intervention for growth failure in early childhood in CF patients. Specifically, investigators hypothesized that oral glutathione could effectively treat CF growth failure in pediatric patients.
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 Months 至 10 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Cystic Fibrosis by either of the following criteria: >60 sweat chloride test or paired deleterious DNA cystic fibrosis transmembrane conductance regulator (CFTR) mutations (Ambry genetics, Genetech or ARUP);
- •Pancreatic insufficient as defined by doctor's prescription of pancreatic enzymes.
排除标准
- •Hospitalized for bowel obstruction or surgery in the six months prior to enrollment;
- •had had a pulmonary exacerbation or oral steroid use or IV antibiotics within one month of enrollment,
- •who had been taking either GSH or N-acetyl cysteine (NAC) within the 12 month period immediately prior to the trial,
- •chronically infected with Burkholderia cepacia.
结局指标
主要结局
Weight Percentile at 3 Months
时间窗: 3 months
Weight Percentile at 3 months adjusted for sex and age
Height Percentile
时间窗: 6 Months
The subjects were measured over the course of the study to determine if treatment improved height percentile.
BMI Percentile
时间窗: 6 months
Body Mass Index percentile adjusted for sex and age. Not available for participants under 2 years of age.
Weight Percentile
时间窗: 6 months
Weight percentile, adjusted for sex and age
Fecal Calprotectin
时间窗: 6 months
Fecal Calprotectin, a measure of gut inflammation, was measured to see if the treatment decreased this outcome.
次要结局
- Forced Vital Capacity(6 months)
- FEV1(6 months)
- Bacteriology(6 Months)
- C-Reactive Protein (CRP)(6 months)
- White Blood Cell Count(6 months)
- Vitamin E(6 months)
- Alanine Aminotransferase (ALT)(6 Months)
- Frequency of Abdominal Pain(6 months)
- Severity of Abdominal Pain(6 months)
- Frequency of Belching(6 months)
- Severity of Belching(6 months)
- Severity of Bloating(6 months)
- Frequency of Flatulence(6 months)
- Severity of Flatulence(6 months)
- Frequency of Lack of Appetite(6 months)
- Severity of Lack of Appetite(6 months)
- Frequency of Bloating(6 months)
- Frequency of Nausea(6 months)
- Severity of Nausea(6 months)
- Frequency of Vomiting(6 months)
- Severity of Vomiting(6 months)
- Frequency of Heart Burn(6 months)
- Severity of Heart Burn(6 months)
- Frequency of Diarrhea(6 months)
- Severity of Diarrhea(6 months)
- Frequency of More Than 2 Bowel Movements Per Day(6 months)
- Severity of More Than 2 Bowel Movements Per Day(6 months)
- Frequency of Less Than 2 Bowel Movements Per Week(6 months)
- Severity of Less Than 2 Bowel Movements Per Week(6 months)
研究者
Clark Bishop
Co investigator
Brigham Young University