Effect of Acid Blockade on Microbiota and Inflammation in Cystic Fibrosis (CF)
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 2
- 主要终点
- Changes in the microbiota and inflammation
研究概览
简要总结
Mucus in the airways of patients with CF represents an area for bacteria proliferation, microbial infection and inflammation. Similar to the lung, the esophagus provides an environment for bacterial to grow. The overall goal of this proposal is to characterize the esophageal microbiota of children with CF that are treated or untreated with acid blockade medication and to measure its possible impact on respiratory disease to develop novel treatment strategies.
详细描述
Patients with cystic fibrosis (CF) have significant morbidity and mortality due to airway infections. These infections are related to the deficiency of mucociliary clearance due to thick dehydrated secretions. Thus, considerable effort is spent managing airway infections. This includes therapies to improve mucus clearance and antibiotic treatments that target important pathogens. Understanding the source of airway microbiota, increased risk of infection, and exacerbation is critical to improve management of airway infection. A large proportion of CF patients are also treated with anti-acid medications. These medications decrease symptoms associated with gastroesophageal reflux disease (GERD), and improve the efficacy of enzyme replacement therapies. Critical for this proposal is the fact that aspiration may represent a potential route for airway infection from microorganisms in the upper gastrointestinal (GI) tract, and anti-acid treatments shift the GI microbiota. In preliminary studies we have identified a strong alteration of the esophageal microbiota in subjects using acid blocking medications. Thus, these treatments may have a significant effect on the bacterial communities present in the upper GI tract and may play a role in infection and exacerbation in CF. Traditionally, access to the upper GI tract has required endoscopy to acquire biopsy tissue, which is an invasive procedure and not routinely performed in CF. To circumvent the invasive sampling required for study of the esophagus we have recently shown that a minimally invasive test, the esophageal string test (EST), is capable of sampling the upper GI tract, and has performance comparable to biopsy for a number of measurements including assessment of the esophageal microbiota.
The primary hypothesis for this proposal is that acid blockade medication alters the esophageal microbiota in CF, increasing the presence of pathogenic bacteria and inflammation. To test this hypothesis we propose three Specific Aims:
Specific aim 1: Determine whether esophageal microbial composition in children with CF changes after withdrawal of acid blockade
- Comparison of esophageal bacterial load by 16S qPCR in subjects on acid blockade and after withdrawal
- Examine the stability of the esophageal bacterial communities based on longitudinal collection of the esophageal string test (EST) prior to withdrawal of acid blockade treatment.
- Determine if there are changes after withdrawal of acid blockade in both sputum microbiota composition and esophageal microbiota (including presence of pathogenic bacteria) and whether the changes are correlated across the two sample types.
Specific aim 2: Determine whether esophageal microbiota in children with CF changes after initiation of acid blockade in patients started for clinical indications
研究设计
- 研究类型
- Observational
- 观察模型
- Case Crossover
- 时间视角
- Prospective
入排标准
- 年龄范围
- 10 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages 10-21 years
- •Known diagnosis of CF based on sweat chloride > 60 mEq/L or identification of two known Cystic fibrosis transmembrane conductance regulator (CFTR) mutations
- •Clinically stable pulmonary disease defined by
- •clinical impression of patient's primary CF provider,
- •no newly prescribed antibiotic treatments in the 30 days prior to enrollment, and
- •relativly stable lung function with a forced expiratory volume in 1 second (FEV1) within 10% of baseline.
- •Male and female
- •Willing to participate in and comply with all study procedures, and
- •Willingness of the subject, parent or legally authorized representative to provide written informed consent.
- •Body Mass Index (BMI) >25%
- •Willing to stop acid blockade medication for 6 weeks for aim
- •Not on acid blockade for 6 weeks for aim 2.
排除标准
- •FEV1 less than 40% predicted
- •History of meconium ileus, distal intestinal obstructive syndrome, gastrointestinal surgery, or intestinal stricture.
- •CF liver disease with cirrhosis, gastric or esophageal varices.
- •Unwilling to participate in and comply with the study procedures.
- •Unwillingness of the subject, parent or legally authorized representative to provide written informed consent.
- •Unwilling or unable to swallow the capsule with the esophageal string test (EST).
- •Gelatin allergy.
- •History of esophageal surgery including fundoplication, or
- •Presence of a gastrostomy tube.
- •Confirmed or suspected diagnosis of Gastroesophageal Reflux Disease (GERD)
研究组 & 干预措施
ON PPI
Subjects on proton pump inhibitor (PPI) treatment
干预措施: PPI treatment (Drug)
结局指标
主要结局
Changes in the microbiota and inflammation
时间窗: Baseline and 6 weeks
Identification of bacterial communities and IL-8
次要结局
未报告次要终点