Sinus Disease in Young Children With Cystic Fibrosis

Recruiting

• Conditions: Olfactory Impairment; Cystic Fibrosis; Chronic Rhinosinusitis (Diagnosis); Cystic Fibrosis in Children; Olfactory Disorder
• Interventions: Drug: Ivacaftor or elexacaftor/tezacaftor/ivacaftor

• Registration Number: NCT06191640
• Lead Sponsor: University of California, Los Angeles

Brief Summary

This is a prospective, observational study examining the impact of highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators on chronic rhinosinusitis (CRS) and olfactory dysfunction (OD) in young children with cystic fibrosis (YCwCF). This study involves two groups: children 2-8 years old, inclusive at initial visit, receiving highly effective modulator therapy (HEMT), and a control group of children 2-8 years old, inclusive at initial visit, not receiving HEMT. Outcomes will include sinus magnetic resonance imaging (MRI) scans, olfactory tests, and quality of life surveys obtained over a two-year period.

Detailed Description

This multi-center, prospective, observational study investigates the effects of highly effective modulator therapy (HEMT) on chronic rhinosinusitis (CRS) and olfactory dysfunction (OD) in young children with cystic fibrosis (YCwCF). The study spans two years and includes two distinct groups of children with cystic fibrosis: children ≤ 8 years old receiving HEMT and a control group of children ≤ 8 not receiving HEMT. The study aims to assess the efficacy of HEMT in improving sinus health and olfactory capabilities in this young demographic.

Key assessments include magnetic resonance imaging (MRI) sinus opacification, olfactory bulb volume measured via MRI, objective olfactory testing, and various quality (QOL) surveys. This investigation seeks to characterize the severity of CRS and OD in YCwCF, and to elucidate if early initiation of HEMT improves CRS and OD .

In the HEMT group, participants will have a pre-HEMT assessment followed by 1-year and 2-year post-HEMT evaluations. In the control/non-HEMT group, participants will undergo parallel assessments at baseline, 1-year, and 2-year intervals to track the natural progression of CRS and OD without HEMT.

Study Timeline

• Study Start: 2023-04-12
• Study First Submitted: 2023-12-19
• Study First Submitted QC: 2023-12-19
• Study First Posted: 2024-01-05
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-08
• Last Update Posted: 2024-07-09
• Primary Completion: 2026-04
• Study Completion: 2026-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

HEMT Group:

• Children with documentation of a CF diagnosis
• Age 2-8 years old at first study visit
• CFTR mutation consistent with FDA labeled indication of highly effective modulator therapy (ivacaftor or elexacaftor/tezacaftor/ivacaftor)
• Clinician intent to prescribe ivacaftor or ETI so that enrollment is before start of HEMT

Non-HEMT/Control Group:

• Children with documentation of a CF diagnosis
• Age 2-8 years at first study visit
• Ineligible for highly effective modulator therapy (ivacaftor or elexacaftor/tezacaftor/ivacaftor) based on CFTR mutation or clinical decision not to initiate HEMT if eligible

Exclusion Criteria

For Both Groups:

• Use of an investigational drug within 28 days prior to the first study visit
• Use of ivacaftor or elexacaftor/tezacaftor/ivacaftor within the 180 days prior to and including the first study visit
• Use of chronic oral corticosteroids within the 28 days prior to and including the first study visit.
• Sinus surgery within 180 days prior to the first study visit

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
HEMT Group	Ivacaftor or elexacaftor/tezacaftor/ivacaftor	Children with CF planning to start ivacaftor or elexacaftor/tezacaftor/ivacaftor CFTR modulator therapy. Participants from the non-HEMT group of this study may enroll into the HEMT cohort if they become eligible for these CFTR modulator therapies and plan to start them.

Primary Outcome Measures

Name	Time	Method
Change in olfactory bulb volume	Baseline, 1-year, and 2-year follow-up	Assessment includes segmenting the olfactory bulb on consecutive coronal slices using MRI, then combining these into a 3-dimensional region. The volume of this region is then calculated in cubic millimeters (mm3).
Change in MRI sinus opacification	Baseline, 1-year, and 2-year follow-up	Measurement involves calculating percent total sinus opacification (%) using MRI, where sinus contents are differentiated into air and soft tissue/fluid.

Secondary Outcome Measures

Name	Time	Method
Change in Pediatric Smell Wheel (PSW) Scores	Baseline, 1-year, and 2-year follow-up	The PSW test involves children identifying microencapsulated odorants. The score (Range: 0-11) is based on the number of correctly identified smells, with higher scores indicating better olfactory function.
Change in Sinus and Nasal Quality of Life Survey (SN-5) - Overall Quality of Life (QOL) Domain	Baseline, 1-year, and 2-year follow-up	SN-5 is a parent-completed survey assessing sinus symptoms and QOL in children. It captures sinus infections, nasal obstruction, allergy symptoms, emotional distress, activity limitations, and overall QOL. The final question assessing the child's overall QOL as a result of nose or sinus problems is scored on a scale 0-10, with higher scores indicating better QOL.
Olfactory Cleft Opacification	Baseline, 1-year, and 2-year follow-up	Olfactory cleft opacification is quantified by segmenting the olfactory cleft on MRI and applying pixel intensity thresholds to calculate the percentage (%) of opacification.
Change in Sinus and Nasal Quality of Life Survey (SN-5) - Symptom Frequency Domains	Baseline, 1-year, and 2-year follow-up	SN-5 is a parent-completed survey assessing sinus symptoms and QOL in children. It captures sinus infections, nasal obstruction, allergy symptoms, emotional distress, activity limitations, and overall QOL. For the first five symptom domain questions, scores range 1-7 for each domain, higher scores indicating higher frequency at which symptom affected patient over the past 4 weeks.
Change in Brief Questionnaire of Olfactory Disorders (BQOD) Scores	Baseline, 1-year, and 2-year follow-up	This BQOD is a parent-completed survey for assessing olfactory-specific quality of life (QOL). The survey scores (Range: 0-21) quantify the degree of olfactory QOL impairment, with higher scores indicating greater olfactory QOL impairment.

Trial Locations

Locations (6)

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States

University of Iowa; 🇺🇸 Iowa City, Iowa, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

University of Vermont; 🇺🇸 Colchester, Vermont, United States

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States