Sinus Disease in Young Children With Cystic Fibrosis

Cystic Fibrosis Clinical Trial

Official title:

Sinus Disease in Young Children With Cystic Fibrosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06191640
• Other study ID #: 22-000594
• Status: Recruiting
• Start date: April 12, 2023
• Est. completion date: April 2026

Study information

• Verified date: January 2024
• Source: University of California, Los Angeles
• Contact: Daniel M Beswick, MD
• Phone: 310-206-8457
• Email: dbeswick[@]mednet.ucla.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: April 2026
• Est. primary completion date: April 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 8 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Rhinosinusitis (Diagnosis)
• Cystic Fibrosis
• Cystic Fibrosis in Children
• Fibrosis
• Olfaction Disorders
• Olfactory Disorder
• Paranasal Sinus Diseases

Intervention

Drug:
• Ivacaftor or elexacaftor/tezacaftor/ivacaftor
HEMT's are prescribed at the discretion of the treating physician and is not dictated by the principal investigator of this study.

Locations

Country	Name	City	State
United States	Children's Hospital Colorado	Aurora	Colorado
United States	University of Virginia	Charlottesville	Virginia
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	University of Vermont	Colchester	Vermont
United States	University of Iowa	Iowa City	Iowa
United States	University of Kansas Medical Center	Kansas City	Kansas

Sponsors (7)

Lead Sponsor	Collaborator
University of California, Los Angeles	Children's Hospital Colorado, Children's Hospital Medical Center, Cincinnati, University of Iowa, University of Kansas Medical Center, University of Vermont, University of Virginia

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in MRI sinus opacification	Measurement involves calculating percent total sinus opacification (%) using MRI, where sinus contents are differentiated into air and soft tissue/fluid.	Baseline, 1-year, and 2-year follow-up
Primary	Change in olfactory bulb volume	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).	Baseline, 1-year, and 2-year follow-up
Secondary	Change in Pediatric Smell Wheel (PSW) Scores	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.	Baseline, 1-year, and 2-year follow-up
Secondary	Olfactory Cleft Opacification	Olfactory cleft opacification is quantified by segmenting the olfactory cleft on MRI and applying pixel intensity thresholds to calculate the percentage (%) of opacification.	Baseline, 1-year, and 2-year follow-up
Secondary	Change in Brief Questionnaire of Olfactory Disorders (BQOD) Scores	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.	Baseline, 1-year, and 2-year follow-up
Secondary	Change in Sinus and Nasal Quality of Life Survey (SN-5) - Symptom Frequency Domains	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.	Baseline, 1-year, and 2-year follow-up
Secondary	Change in Sinus and Nasal Quality of Life Survey (SN-5) - Overall Quality of Life (QOL) Domain	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.	Baseline, 1-year, and 2-year follow-up