The Return of the Pancreas: Evaluating Impact of CFTR Modulators on Pancreatic Function
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 1
研究概览
简要总结
The goal of this clinical trial is to evaluate the safety of stopping pancreatic enzyme replacement therapy (PERT) in children with cystic fibrosis (CF) receiving CFTR modulator therapy (CFTRm) who have regained pancreatic sufficiency. The main questions it aims to answer are:
- Does discontinuation of PERT affect gastrointestinal symptoms, nutritional status, pancreatic function, or body composition over 6 months?
- Does stopping PERT increase gastrointestinal symptoms or affect nutritional status, pancreatic function, or body composition compared with continuing PERT?
Researchers will evaluate changes in growth, gastrointestinal symptoms, vitamin levels, pancreatic function, and body composition following PERT discontinuation.
Participants will:
- Complete study visits and assessments over 6 months
- Continue or discontinue PERT based on study assignment
- Undergo anthropometric measurements
- Complete questionnaires about gastrointestinal symptoms
- Provide blood samples to assess vitamin levels and coagulation markers
- Provide stool samples to measure fecal elastase-1 (FE-1) and evaluate pancreatic function
详细描述
This prospective clinical trial will evaluate the safety and feasibility of discontinuing pancreatic enzyme replacement therapy (PERT) in children with cystic fibrosis (CF) who regain pancreatic sufficiency after treatment with cystic fibrosis transmembrane conductance regulator modulators (CFTRm).
Pancreatic insufficiency is a common complication of CF and is typically treated with lifelong PERT. Recent studies and case reports have shown that some individuals receiving CFTR modulators experience improvement or normalization of pancreatic function, as measured by fecal elastase-1 (FE-1) levels. However, there is limited evidence regarding the safety of stopping PERT after pancreatic function recovery. This study aims to address this knowledge gap by prospectively evaluating growth, gastrointestinal symptoms, nutritional status, and pancreatic function after PERT withdrawal.
Eligible participants are children and adolescents aged 18 years or younger with cystic fibrosis and a history of pancreatic insufficiency who are receiving CFTR modulator therapy. Participants will undergo fecal elastase testing at enrollment and will be assigned to study groups based on pancreatic function status. Participants with FE-1 levels ≥200 µg/g will discontinue PERT under medical supervision, while participants with FE-1 levels <200 µg/g will continue standard therapy.
Study assessments will include growth measurements, gastrointestinal symptom questionnaires, laboratory monitoring of fat-soluble vitamins and liver function, CFTR modulator trough levels, and repeat fecal elastase testing. Body composition will also be evaluated. Participants who discontinue PERT will undergo close clinical monitoring throughout the study period for signs of malabsorption, poor weight gain, recurrent pancreatic insufficiency, or pancreatitis. PERT may be restarted if clinically indicated.
The study will also explore factors associated with successful recovery of pancreatic function and sustained pancreatic sufficiency, including demographic characteristics, nutritional status, medication history, and laboratory markers. In addition, optional biospecimen storage will allow future analyses of the metabolome and microbiome related to pancreatic function and CFTR modulator response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 0 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of cystic fibrosis.
- •History of pancreatic insufficiency, documented by a prior fecal elastase-1 (FE-1) concentration <200 µg/g stool.
- •Current pancreatic sufficiency at study entry, defined as fecal elastase-1 (FE-1) concentration ≥200 µg/g stool after treatment with a CFTR modulator.
- •Age ≤18 years.
- •Current use of a CFTR modulator, including ivacaftor, elexacaftor/tezacaftor/ivacaftor, or vanzacaftor/tezacaftor/deutivacaftor.
排除标准
- •CF-related diabetes requiring current insulin use
- •Advanced CF liver disease as defined by nodular liver, advanced fibrosis (F4), multi-lobular cirrhosis with or without portal hypertension, non-cirrhotic portal hypertension
- •Short gut syndrome as defined by need for surgical bowel resection and subsequent need for parenteral nutrition for > 60 days or bowel length less than 25%
- •Moderate to severe malnutrition, defined as a BMI-for-age z score ≤ -2 for participants aged ≥2 years or a weight-for-length z score ≤ -2 for participants aged <2 years
研究组 & 干预措施
Intervention: Discontinuation of Pancreatic Enzyme Replacement Therapy
Participants with cystic fibrosis who demonstrate pancreatic sufficiency, defined as fecal elastase-1 (FE-1) ≥200 µg/g after treatment with CFTR modulator therapy, will discontinue pancreatic enzyme replacement therapy (PERT) under medical supervision. Participants will undergo follow-up assessments over 6 months, including monitoring of growth, gastrointestinal symptoms, nutritional laboratory markers, and repeat fecal elastase testing to evaluate the safety and sustainability of pancreatic function recovery after PERT discontinuation.
干预措施: Discontinuation of Pancreatic Enzyme Replacement Therapy (Drug)
研究者
Molly Bozic
Pediatric Gastroenterology, Hepatology, and Nutrition Fellow
Indiana University