Clinical trial NCT04458129: Polyethylene Glycol and Intestinal Inflammation in Cystic Fibrosis
Official title: EFFECT OF POLYETHYLENE GLYCOL TREATMENT ON INTESTINAL INFLAMMATION ASSOCIATED WITH CYSTIC FIBROSIS IN CHILDREN
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis
intestinal inflammation
fecal calprotectin
microbiota
children
polyethylene glycol
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2020-07-07
Enrollment: 23
Sex: ALL
Minimum age (years): 4
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Bi-centric, non-comparative, prospective, Phase II trial according to a Fleming scheme.
Primary purpose: TREATMENT

Brief summary: The main objective of the study is to evaluate the effectiveness of polyethylene glycol treatment on intestinal inflammation in children with cystic fibrosis. In this test, a method adapted from the Fleming one-step scheme will be used. The success rate is measured by the proportion of patients with fecal calprotectin levels \< 250 µg/g at 3 months after treatment initiation.

Detailed description: Cystic fibrosis is one of the most frequent serious genetic diseases in France (7000 patients). It is the consequence of mutations in the CFTR gene, encoding a protein involved in the hydro-electrolytic balance of secretions. Beyond the well-known lung damage in these patients, intestinal inflammation is present in the majority of patients.

While advances in the management of cystic fibrosis are increasing patient life expectancy, other issues are emerging, including the impact of this chronic intestinal inflammation on the nutritional status and high risk of digestive cancers (Maisonneuve, 2013; Garg and Ooi, 2017; Yamada, 2018).

Currently, no management is proposed to treat this intestinal inflammation. The use of laxatives to fluidize digestive secretions and restore a digestive ecosystem close to the healthy subject could constitute a new therapeutic approach to this intestinal inflammation, as previously shown in the mouse model of cystic fibrosis (De Lisle, 2007). However, to date, to the investigator's knowledge, no studies have evaluated the effect of laxative treatment on intestinal inflammation of cystic fibrosis in humans.

This study is a bi-centric, non-comparative, prospective study for a phase II trial according to a Fleming scheme.

Study participants will take a 3-month laxative treatment with polyethylene glycol for 3 months. In addition to the inclusion visit, a follow-up visit will take place at 3 months and 3 intermediate telephone calls will be made to ensure efficacy, tolerance and compliance.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 4 years old and \<18 years old ;
* Patient with cystic fibrosis (sweat test \> 60 mmol/l and/or molecular biology identifying mutations in the CFTR gene) with associated pancreatic insufficiency (fecal elastase \<100 µg/g);
* With a rapid calprotectin assay result via the IBDoc test (Bühlmann®) superior or equal to 250 µg/g;
* Person affiliated or benefiting from a social security scheme;
* Free, informed and written consent signed by the holders of parental authority and the investigator before any examination required by the research and oral and/or written consent by the participant (depending on his/her age).

Exclusion Criteria:

* Ongoing processing that can modulate the functionality of the CFTR (such as lumacaftor-ivacaftor protein therapy);
* Patient already on polyethylene glycol or other laxative within 3 months before the inclusion visit;
* Patient with diarrhea at inclusion (diarrhea will be defined as the presence of 3 or more stools / day in the 7 days prior to the inclusion visit);
* Acute viral or bacterial diarrhea in the month prior to the inclusion visit (associated with fever);
* Cure of oral or intravenous antibiotics or antifungals in the month preceding the collection of samples;
* Change in background treatment in the month prior to the inclusion visit (oral or inhaled corticosteroid therapy, azithromycin, inhaled antibiotic therapy, inhaled antifungal agent, proton pump inhibitors);
* Taking probiotics in the month before the inclusion visit;
* Transplanted patient (on immunosuppressants);
* Patient with IBD or celiac disease;
* Patient with digestive perforation or risk of digestive perforation;
* Patient with ileus or suspicion of intestinal obstruction, symptomatic stenosis;
* History of hypersensitivity to macrogol or any of the excipients
* Holders of parental authority enjoying judicial protection.

Primary outcomes:
measure: Impact of a 3-month polyethylene glycol treatment on intestinal inflammation assessed by measurement of fecal calprotectin (µg / g) by an ELISA biological test
timeFrame: 3 months after the inclusion visit i.e. 3 months after the initiation of treatment with polyethylene glycol
Secondary outcomes:
measure: Evolution of the digestive inflammatory response, assessed by measurement of fecal calprotectin (µg / g)
timeFrame: Change from Baseline fecal calprotectin measurement at 3 months
measure: Evolution of the digestive inflammatory response, assessed by Analysis of the expression of genes involved in the inflammatory and pro-oncogenic response
timeFrame: Change from Baseline measurement at 3 months
measure: Evolution of the digestive symptoms, assessed by the JenAbdomen CF-score
timeFrame: Change from Baseline measurement at 3 months
measure: Evolution of the quality of life scores, assessed by the CFQ-R questionnaire
timeFrame: Change from Baseline measurement at 3 months
measure: Evolution of the composition of the bacterial intestinal microbiota
timeFrame: Change from Baseline measurement at 3 months
measure: Evolution of the composition of the fungal intestinal microbiota
timeFrame: Change from Baseline measurement at 3 months
measure: Evolution of the pulmonary inflammation, assessed by the dosage of calprotectin in the sputum
timeFrame: Change from Baseline measurement at 3 months
Other outcomes:
Locations:
Study officials:
affiliation: CHU de Toulouse - Hôpital des Enfants - Centre de Ressources et de Compétences de la Mucoviscidose (CRCM) pédiatrique
name: Marie M MITTAINE, MD
role: PRINCIPAL_INVESTIGATOR
References: