Effect of Lumacaftor/Ivacaftor in Children With Cystic Fibrosis Homozygote for F508del on Small Airway Function (ROOTS)

Real World Data of the Effect of Lumacaftor/Ivacaftor Therapy in Children With Cystic Fibrosis Homozygote for F508del on Small Airway Function

To obtain prospective real world data of the effect of lumacaftor/ivacaftor or tezacaftor/ ivacaftor on small airway disease in children aged 6-18 years with cystic fibrosis (CF) homozygous for F508del. The effect of the medication on small airway disease is evaluated by measurement of multiple breath washout (MBW) with its outcome parameter lung clearance index (LCI) and the Perth-Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF) cpmputed tomography (CT) score. In addition the relation between changes in LCI and PRAGMA-CF score is evaluated.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis in Children

Detailed Description

Multi-center observational study. Duration 12 months after the start of lumacaftor/ ivacaftor or tezacaftor/ ivacaftor .

To collect these data and to assist in clinical decisions regarding initiation and continuation of lumacaftor/ivacaftor or tezacaftor/ ivacaftor, the investigators of the CF center (Beatrix Children's Hospital, University Medical Center Groningen (UMCG), the Netherlands) developed an extensive protocol of testing before children aged 6-18 years start therapy and during the first year after start.

The protocol includes the following tests: growth parameters, sweat test, lung function testing (spirometry, MBW, body plethysmography), blood test panel (AST, ALT, alkalic phosphatase (AF), total and direct bilirubin, LDH), fecal elastase, high resolution (HR)CT and CF quality of life questionnaires. These tests are repeated at regular intervals.

Multi-center observational study. Duration 12 months after the start of lumacaftor/ ivacaftor or tezacaftor/ ivacaftor .

• Study Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

• Study Contact: Name: Annelies M Zwitserloot, MD; Phone Number: +31625649950; Email: a.m.zwitserloot@umcg.nl
• Study Contact Backup: Name: Brigitte WM Willemse, MD, phd; Phone Number: +31503616161; Email: b.w.m.willemse@umcg.nl

Study Locations

• Germany
  • Düsseldorf, Germany
    • Children's Hospital Marien Hospital Wesel
• Netherlands
  • Groningen, Netherlands
    • Beatrix Children's Hospital, University Medical Center Groningen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Patients are included from the Beatrix Children's Hospital, UMCG, the Netherlands and the Marien Hospital Wesel, Germany

Description

Inclusion Criteria:

• Children aged 6-18 years
• CF, Homozygote F508del confirmed by DNA analysis
• Considered for start of lumacaftor/ ivacaftor or tezacaftor/ivacaftor

Exclusion Criteria:

• - Unable to perform acceptable, repeatable lung function tests

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
CF patients aged 6-18 years homozygeous for delta F508; CF patients aged 6-18 years homozygeous for delta F508 starting with lumacaftor/ ivacaftor or tezacaftor/ ivacaftor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in lung clearance index	Change between t=0 and t=12	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in PRAGMA-CF score	Change between t=0 and t=12	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
percent predicted forced expiratory volume in 1 second	t= 0 and t-=12	12 months
percent predicted forced vital capacity measured by spirometry	Change between t=0 and t=12	12 months
Residual volume measured by blodypethysmography	Change between t=0 and t=12	12 months
Residual volume/ total lung capacity measured by blodypethysmography	Change between t=0 and t=12	12 months
Mid upper arm circumference in SDS	Change between t=0 and t=12	12 months
Weight SDS	Change between t=0 and t=12	12 months
Sweat chloride level	Change between t=0 and t=12	12 months
CF questionnaire revised respiratory domain	Change between t=0 and t=12, scale 0-100	12 months

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Collaborators: Vertex Pharmaceuticals Incorporated; Marien Hospital Wesel

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2017
• Primary Completion (Actual): July 19, 2022
• Study Completion (Actual): July 19, 2022

Study Registration Dates

• First Submitted: September 18, 2019
• First Submitted That Met QC Criteria: October 23, 2019
• First Posted (Actual): October 24, 2019

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Lung clearance index; Multiple breath washout; lumacaftor/ ivacaftor; tezacaftor/ ivacaftor; PRAGMA CF score
• 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: 201900032

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plans to share IPD

Drug and device information, study documents

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