Chronic Rhinosinusitis (Diagnosis), Cystic Fibrosis, Cystic Fibrosis in Children, Olfactory Disorder, Olfactory Impairment
Conditions
Keywords
Cystic Fibrosis, Chronic Rhinosinusitis, Olfactory Dysfunction
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.
Interventions
HEMT's are prescribed at the discretion of the treating physician and is not dictated by the principal investigator of this study.
Sponsors
University of California, Los Angeles
University of Kansas Medical Center
Children's Hospital Medical Center, Cincinnati
University of Iowa
University of Virginia
University of Vermont
University of North Carolina, Chapel Hill
Children's Hospital Colorado
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
2 Years to 8 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 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. |
| 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 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. |
Countries
United States
Contacts
CONTACTDaniel M Beswick, MD
CONTACTMarlene Florian
PRINCIPAL_INVESTIGATORDaniel M Beswick, MD
University of California, Los Angeles
Outcome results
None listed