The Impact of Elexacaftor/Tezacaftor/Ivacaftor on Nutrition, the Gut Microbiome, and Gut Inflammation
Maribeth Nicholson, MD
BACKGROUND: Cystic Fibrosis (CF) is associated with significant gastrointestinal manifestations with accompanying growth failure and intestinal inflammation. Gastrointestinal morbidities including obstructive intestinal diseases, malabsorption, pancreatic insufficiency, gastrointestinal inflammation, and liver dysfunction affect approximately 50-90 percent of CF patients each year. The recent FDA approval of therapies that rescue the CF receptor function (modulators) have demonstrated significant improvement in pulmonary outcomes based on landmark studies and have been transformative in lengthening CF survival. GAP: In clinical trials, the newest 2019 FDA approved pharmaceutical modulator ELX/TEZ/IVA demonstrated improved pulmonary effects, but the impact of ELX/TEZ/IVA on growth outcomes, the gastrointestinal microbiome, and gastrointestinal inflammation in pediatric patients with CF remains unknown. HYPOTHESIS: We hypothesize that ELX/TEZ/IVA will improve BMI and associated nutritional parameters in pediatric CF patients. We also hypothesize that the bacterial diversity in the gastrointestinal tract will be significantly lower in CF patients before starting ELX/TEZ/IVA compared to after. Finally, we anticipate that intestinal inflammation, as measured through fecal calprotectin, will be decreased in CF patients after the initiation of ELX/TEZ/IVA. METHODS: This is a longitudinal prospective study collecting sequential stool samples and clinical metadata at three time points over one year. RESULTS: Pending. Currently starting patient enrollment. IMPACT: The successful completion of the aims detailed in this proposal will help identify the role of ELX/TEZ/IVA in improving nutritional factors in pediatric CF patients and therefore determining the need for additional treatment approaches.