Quality of Life and Gut Health in Pediatric Patients With Cystic Fibrosis

Probiotic Supplementation, Quality of Life and Gut Health in Pediatric Patients With Cystic Fibrosis

The aim of the present study is to investigate the effect of probiotic supplementation on GI related quality of life, through a randomised placebo-controlled clinical trial. Moreover, the invetigators wish to study CF microbiota and intestinal inflammation in the setting of probiotic supplementation and newly started treatment with a highly effective CF-specific treatment, elexacaftor-tezacaftor-ivacaftor (ETI). The proposed project has the potential to increase QoL and decrease GI morbidity in children with CF. If successful, the results of this study can contribute to alter the care of CF patients by including supplementation of probiotics in routine CF care. Morever, the study can provide much needed insights to GI microbiota and inflammation in pediatric CF patients.

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis in Children
• Intervention / Treatment: Dietary supplement: Multistrain Probiotic; Dietary supplement: Placebo - maltodextrin

Detailed Description

The project targets pediatric patients with cystic fibrosis (CF), and has to work packages (WP). WP1 is an observational study, and WP2 is a randomised placebo-controlled clinical trial. The goal of the study is to investigate the effect of probiotics on pediatric CF patients' quality of life (QoL). Moreover the investigators wish to explore effects of both a highly effective CFTR modulator and probiotics on gut microbiota and intestinal inflammation.

The primary question it aims to answer are:

• Can probiotics improve GI related QoL in children with CF?

Secondary aims are to:

• Investigate GI microbiota and GI inflammation before and after commencement of the highly effective triple-combination elexacaftor-tezacaftor-ivacaftor (ETI)
• Explore GI microbiota before and after treatment with probiotics vs. placebo
• Study intestinal inflammation before and after treatment with probiotics vs. placebo
• Examine body composition and its relation to lung function

In WP1 participants will during routine examination before starting treatment with ETI be asked to deliver stool samples, and fill in QoL questionnaires. In WP2 participants will be randomized to intervention with probiotics or placebo, and the same parameters as in WP1 will also be collected.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway
    • Recruiting
    • Oslo University Hospital
    • Contact: Magnhild P Kolsgaard, PhD; Phone Number: 0047 41514045; Email: uxpoma@ous-hf.no
    • Contact: Camilla Styffe Sæland, Master; Phone Number: 004793257798; Email: casael@ous-hf.no
    • Principal Investigator: Magnhild P Kolsgaard, PhD
    • Sub-Investigator: Camilla Styffe Sæland, Master
    • Sub-Investigator: Linh Dieu Ngo, Master

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria for WP1:

• CFTR mutations eligible for treatment with ETI
• Age 2-18 years. Majority of patients will be 2-6 years of age as ETI was approved from 6 years of age in 2022, and will be available for children above 2 years from 2024.
• Included in the Norwegian CF Register and consented to participation in CF general research biobank

Exclusion criteria for WP1:

• Other CFTR modulators commenced the last 6 months before inclusion
• Use of probiotics or prebiotics last 2 months
• Current pulmonary exacerbation

Inclusion criteria for WP2:

• Age 3-18 years
• CFTR modulator treatment naïve or treated with CFTR modulator for at least 6 months
• Included in the Norwegian CF Register and consented to participation in CF general research biobank

Exclusion criteria for WP2:

• CFTR modulators commenced the last 6 months before inclusion
• Use of probiotics or prebiotics last 2 months
• Current pulmonary exacerbation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotics; Participants will recieve a multi-strain probiotic daily for 6 months	Dietary supplement: Multistrain Probiotic; Participants will recieve a multi-strain probiotic daily for 6 months
Sham Comparator: Placebo; Participants will recieve maltodextrin daily for 6 months	Dietary supplement: Placebo - maltodextrin; Participants will recieve placebo/ maltodextri daily for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in GI related QoL using the questionnaire PedsQL GI	PEDsQL GI has been validated for use in the CF population. Participants will be scored before and 6 months after treatment start with ETI (WP2), and before and after 6 months treatment with probiotics vs placebo (WP2).	0-6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in microbiota	Stool samples for microbiota will be collected using a collection kit provided to the participants at recruitment, and then after 6 month of ETI treamtment (WP1), or probiotic/placebo (WP2). Microbiota analysis will be done using 16s rRNA amplicon sequencing and reduced metagenome sequencing.	0-6 months
Changes in intestinal inflammation	Stool samples for gut inflammation markers will be collected using a collection kit provided to the participants at recruitment and after 6 months of ETI treamtment (WP1), or probiotic/placebo (WP2. Levels of calprotectin, neopterin and myeloperoxidase will be measured.	0-6 months

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: Norwegian National Advisory Unit on Rare Disorders, Oslo University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: February 12, 2024
• First Submitted That Met QC Criteria: February 21, 2024
• First Posted (Actual): February 29, 2024

Study Record Updates

• Last Update Posted (Actual): June 13, 2024
• Last Update Submitted That Met QC Criteria: June 12, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Quality of life; Children; Microbiota; Cystic Fibrosis; CFTR modulators; Probiotic supplement; elexacaftor-tezacaftor-ivacaftor
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: 677186

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No