Cystic fibrosis and the role of gastrointestinal outcome measures in the new era of therapeutic CFTR modulation

J Cyst Fibros. 2015 Mar;14(2):169-77. doi: 10.1016/j.jcf.2015.01.006. Epub 2015 Feb 10.

Abstract

With the development of new drugs that directly affect CFTR protein function, clinical trials are being designed or initiated for a growing number of patients with cystic fibrosis. The currently available and accepted clinical endpoints, FEV1 and BMI, have limitations. The aim of this report is to draw attention to the need and the ample possibilities for the development and validation of relevant gastrointestinal clinical endpoints for scientific evaluation of CFTR modulation treatment, particularly in young children and infants. The gastrointestinal tract offers very good opportunities to measure CFTR protein function and systematically evaluate CF related clinical outcomes based on the principal clinical gastrointestinal manifestations of CF: intestinal pH, intestinal transit time, intestinal bile salt malabsorption, intestinal inflammation, exocrine pancreatic function and intestinal fat malabsorption. We present a descriptive analysis of a variety of gastrointestinal outcome measures for clinical relevance, reliability, validity, responsiveness to interventions, feasibility in particular in young children and the availability of reference values.

Keywords: Bile acid metabolism; Clinical trials; Cystic fibrosis; End points; Exocrine pancreatic insufficiency; Fat malabsorption; Gastrointestinal; Intestinal inflammation; Intestinal pH; Intestinal transit time; Outcome measures.

Publication types

  • Review

MeSH terms

  • Child, Preschool
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis* / complications
  • Cystic Fibrosis* / drug therapy
  • Cystic Fibrosis* / genetics
  • Diagnostic Techniques, Digestive System*
  • Drug Monitoring / methods
  • Gastrointestinal Diseases* / diagnosis
  • Gastrointestinal Diseases* / etiology
  • Gastrointestinal Diseases* / metabolism
  • Gastrointestinal Diseases* / physiopathology
  • Genetic Therapy / methods
  • Humans
  • Infant
  • Outcome Assessment, Health Care
  • Reproducibility of Results

Substances

  • Cystic Fibrosis Transmembrane Conductance Regulator