The effect of polyethylene glycol treatment on gut health in Cystic Fibrosis, a pilot study

Gut health in cystic fibrosis (CF) is impaired. The CF gastrointestinal
phenotype is characterized by nutrient malabsorption, dysbiosis and intestinal
inflammation. The prominent role of the gut in numerous metabolic processes and
its influence on other organs has recently become well appreciated. Impaired
gut health in CF is likely to play a important role in CF-related liver disease
as well as metabolic complications such as CF-related diabetes mellitus.
Impaired gut health in CF is also associated with bothersome symptoms as
abdominal discomfort and constipation.
In this study, we aim to evaluate the effects of treatment with polyethylene
glycol (PEG), a commonly prescribed osmotic laxative , on gut health in CF
patients by both clinical symptoms and biochemical parameters. In animal models
of CF, we have recently shown that PEG treatment improves various
gastrointestinal outcomes, among which bile acid homeostasis, which could be
implicated in the pathophysiology of CF-related complications such as diabetes
and liver disease. In addition, others reported that PEG improves intestinal
transit time and reduce small intestinal bacterial overgrowth in CF mice; thus,
by improving gut function, short-term benefits on gastrointestinal symptoms
and general wellbeing are also expected.
Measurements, including both blood and faecal parameters related to gut health
and a quality of life questionnaire, will be collected from CF patients before,
2 weeks after PEG treatment, and after a 2-weeks washout period.
If PEG treatment improves gut health according to the measured parameters, as
it does in animal models, it should be considered as a possible treatment to
improve gut health in CF patients.

Main objective: to assess the effects of PEG treatment on bile acid homeostasis
in cystic fibrosis patients. Secondary objective: to assess the effects of PEG
treatment on gastrointestinal symptoms and quality of life, and on gut
health-related parameters, such as liver function and glucose metabolism.

Longitudinal repeated measures design. Measurements will be at baseline (day
0), after 2 weeks of PEG treatment (day 14) and after 2 weeks of wash-out
period (day 28). Each measurement consists of taking blood, filling a
questionnaire and collect faeces.

Polyethylene glycol + electrolytes (Movicolon) 13.8 gram twice daily for 2
weeks

Intestinal health in CF is impaired, with consequently many possible
complications on gastrointestinal and metabolic processes. With promising
results of PEG in animal studies in improving gut health and mostly bile acid
homeostasis, this study will gain insight in the therapeutic opportunities in
humans. This can have a contribution to the future treatment of CF patients.
The burden for participants will be acceptable. Patients will be asked to visit
the hospital three times for a fasted blood draw and questionnaire.
Additionally, patients will be asked to collect three faecal samples. We expect
no pressing adverse events. Patients are treated with a commonly prescribed
laxative for a period of two weeks. The most common side effects associated
with PEG use are: diarrhea, which might occur in absence of overt constipation,
abdominal distention, stomach pain, stomach cramps, nausea, vomiting,
flatulence, borborygmi. More serious complications as electrolyte disturbances
and allergic reactions are rare. Expected benefit in improvement
gastrointestinal and subjective well-being, especially on the long-term, is
potentially significant.