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

Frank A J A Bodewes*, Henkjan J Verkade, Jan A J M Taminiau, Drucy Borowitz, Michael Wilschanski, Working group C​ystic Fibrosis and Pancreatic Disease of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN)

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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. (C) 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)169-177
Number of pages9
JournalJournal of Cystic Fibrosis
Volume14
Issue number2
DOIs
Publication statusPublished - Mar-2015

Keywords

  • Cystic fibrosis
  • Outcome measures
  • End points
  • Gastrointestinal
  • Clinical trials
  • Intestinal pH
  • Intestinal transit time
  • Bile acid metabolism
  • Intestinal inflammation
  • Exocrine pancreatic insufficiency
  • Fat malabsorption
  • INFLAMMATORY-BOWEL-DISEASE
  • BILE-ACID MALABSORPTION
  • CHAIN FATTY-ACIDS
  • INTESTINAL CURRENT MEASUREMENT
  • ENZYME REPLACEMENT THERAPY
  • GROWTH-FACTOR 19
  • PANCREATIC INSUFFICIENCY
  • BICARBONATE SECRETION
  • FECAL CALPROTECTIN
  • OROCECAL TRANSIT

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