Evaluation of the Capability of a Glycine Oral Supplement for Diminishing Bronchial Inflammation in Children With Cystic Fibrosis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 13
- 试验地点
- 6
- 主要终点
- Changes in Serum Concentration of Inflammatory Biomarkers (Other Than TNF-alpha)
研究概览
简要总结
The aim of this study is to evaluate if glycine, orally administered in a daily dose of 0.5 g/kg during 8 weeks, can ameliorate the airway inflammation in children with cystic fibrosis, as compared with placebo. During all of the study children will receive their usual treatment for cystic fibrosis.
详细描述
Background. Cystic fibrosis (CF) is a genetic disorder caused by a mutation in a gene that codifies for a chloride channel named "cystic fibrosis transmembrane regulator" (CFTR). In the lungs this results in thick and dehydrated mucus that tends to cause obstruction of the bronchial lumen. Neutrophils and proinflammatory substances have been detected in bronchoalveolar lavage fluid of children with CF who have no bacterial infection. This inflammation conditions a vicious circle in which airways are colonized by bacteria that further increase inflammation. Persistent inflammation leads to irreversible changes in airways, which become distorted. Therefore, a key step in CF treatment is reduction of airway inflammation, for which long-term use of corticosteroids, ibuprofen or macrolides may be indicated.
Glycine and its antiinflammatory effect. Glycine is the most simple aminoacid, but it is also an agonist of the glycine receptors (GlyR) that, when activated, cause that cells such as Kupffer cells, alveolar macrophages and neutrophils decrease their sensitivity to proinflammatory agents. Orally administered glycine has been used for some illnesses, and it has been noticed that it is well tolerated. Considering that children with CF have an intense inflammatory process in the airways, here we propose to use glycine as antiinflammatory agent.
Problem statement. Can a glycine oral supplement decrease the airway inflammation in children with CF?
Hypothesis. Compared with placebo, a daily supplement of glycine administered for 8 weeks to children with CF produce a statistically significant decrease of bronchial inflammation, measured by the concentration of neutrophils and inflammatory substances in sputum and peripheral blood, as well as by respiratory symptoms and spirometry.
Main objective: To determine whether a daily supplement of 0.5 g/kg glycine for 8 weeks significantly decrease the concentration, including neutrophils, interleukin(IL)-1β, IL-6, IL-8, tumor necrosis factor alpha (TNF-α), and myeloperoxidase, in sputum and peripheral blood of children with CF.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 5 Years 至 15 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children of either sex
- •Between 5 and 15 years of age
- •With CF diagnosed according to established criteria
- •Without changes in the CF treatment in the last 30 days
- •Without CF exacerbation in the last 30 days
- •Without acute respiratory infection (e.g., common cold) in the last 15 days
- •Informed consent letter signed by their parents or legal guardians
排除标准
- •Children with CF that had participated in a research protocol in the last 3 months
- •Presence of serious adverse effects attributable to glycine, in which case the result will be considered as therapeutic failure in the statistical analysis
- •Development of a CF exacerbation, in which case the available data so far collected will be included in the statistical analysis
结局指标
主要结局
Changes in Serum Concentration of Inflammatory Biomarkers (Other Than TNF-alpha)
时间窗: 8 weeks
To correct for the baseline variability, all measurements were expressed as percentage of baseline (value at week 8 with respect to baseline value \[beginning of the glycine or placebo period, respectively\]). Then, percentages were log-transformed to adjust to a normal distribution.
Changes in Serum Concentration of Inflammatory Biomarkers (TNF-alpha)
时间窗: 8 weeks
To correct for the baseline variability, all measurements were expressed as percentage of baseline (value at week 8 with respect to baseline value \[beginning of the glycine or placebo period, respectively\]). Then, percentages were log-transformed to adjust to a normal distribution.
Changes in Sputum Concentration of Inflammatory Biomarkers (IL-6)
时间窗: 8 weeks
To correct for the baseline variability, all measurements were expressed as percentage of baseline (value at week 8 with respect to baseline value \[beginning of the glycine or placebo period, respectively\]). Then, percentage change was log-transformed to adjust to a normal distribution.
Changes in Sputum Concentration of Inflammatory Biomarkers (G-CSF)
时间窗: 8 weeks
To correct for the baseline variability, all measurements were expressed as percentage of baseline (value at week 8 with respect to baseline value \[beginning of the glycine or placebo period, respectively\]). Then, percentage change was log-transformed to adjust to a normal distribution.
Changes in Sputum Concentration of Inflammatory Biomarkers (Other Than IL-6 and G-CSF)
时间窗: 8 weeks
To correct for the baseline variability, all measurements were expressed as percentage of baseline (value at week 8 with respect to baseline value \[beginning of the glycine or placebo period, respectively\]). Then, percentage change was log-transformed to adjust to a normal distribution.
次要结局
- Changes in Score for Sputum Production, Dyspnea and Global Symptoms(8 weeks)
- Changes in FEV1, FEF25, and FEFmax(8 weeks)
- Changes in Other Spirometric Variables(8 weeks)
- Changes in Pulse Oximetry, FEV1/FVC, and FEF50.(8 weeks)
- Changes in Clinical Data Scores (Other Than Sputum Production, Dyspnea and Global Symptoms)(8 weeks)
研究者
Mario H. Vargas
Senior Researcher
Instituto Nacional de Enfermedades Respiratorias