Proton-Pump Inhibitors and Fat Absorption in Cystic Fibrosis and Pancreatic Insufficiency: A Randomized Crossover Pilot Trial

Abstract

Background: Dietary fat malabsorption contributes to poor nutritional status in patients with cystic fibrosis (CF) and exocrine pancreatic insufficiency (EPI). Prescribing gastric acid-reducing agents such as proton-pump inhibitors (PPI) as an adjunct to pancreatic enzyme replacement therapy (PERT) to improve dietary fat absorption has been accepted in clinical practice despite limited evidence.

Aims: This was a pilot randomized, double-blind, placebo-controlled crossover trial of subjects aged 12 and older with CF and EPI assessed on placebo and omeprazole to determine if PPI improved the efficacy of PERT as indicated by measures of dietary fat absorption.

Methods: Fat malabsorption via stool coefficient of fat absorption (CFA) and malabsorption blood test (MBT), gastrointestinal pH (wireless motility capsule [WMC]), and quality of life (QOL) were assessed after 14 days on both placebo or PPI (omeprazole).

Results: Total 19 subjects enrolled, 13 were randomized, and 9 provided paired results on placebo and PPI. The 3 subject results for CFA were as follows: 1 increased, 1 decreased, and 1 was within the reference range in both tests for fat absorption. For 9 MBT subjects, 7 decreased and 2 increased fat absorption. For the 4 WMC studies, no change in transit times, nor in pH profiles were noted. No differences were seen in the domains of the two QOL questionnaires comparing placebo and PPI.

Conclusions: These limited descriptive pilot study results in participants with CF and EPI on PERT evaluated by stool, blood, and QOL tests did not suggest improvement in fat absorption attributable to PPI.

Keywords: CFA; Cystic fibrosis; MBT; PERT; Proton-pump inhibitors; WMC.

Fig. 1

Protocol timeline. PPI proton-pump inhibitor, MBT malabsorption blood test, WMC wireless motility capsule

Fig. 2

Measured gastrointestinal transit (a) and post-stomach small intestinal pH (b) profiles on and off treatment. CTT Colonic transit time, GET gastric emptying time, GTT gastric transit time, PPI proton-pump inhibitor, SBTT small bowel transit time, SLBTT small-large bowel transit time, WGTT whole gut transit time

Fig. 3

PROMIS and PROMIS-GI selected domains: 3a Reflux, 3b Belly Pain, 3c Gas and Bloating, 3d Constipation, 3e Adult Pain, and 3f Adult Depression. PROMIS measure domains are reported on a T-score, where 50 is the mean of the reference population. Higher numbers indicate more of the domain being measured. PROMIS Patient-reported outcomes measurement information system

Fig. 4

CFQ-R selected domains: 3a Physical, 3b Emotion, 3c Eating, 3d Treatment Burden, 3e Respiratory, and 3f Digest. The CFQ-R is a disease-specific measure for patients with cystic fibrosis, with higher scores indicating better health-related quality of life in the domain being measured. CFQ-R Cystic fibrosis questionnaire–revised