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A Longitudinal, Observational Study of Primary Ciliary Dyskinesia in Adults

Active, not recruiting
Conditions
Primary Ciliary Dyskinesia
Interventions
Diagnostic Test: Spirometry
Diagnostic Test: Multiple Breath Washout (MBW)
Diagnostic Test: Mucociliary Clearance (MCC)
Diagnostic Test: MRI of the chest
Diagnostic Test: CT of the chest
Registration Number
NCT05685186
Lead Sponsor
ReCode Therapeutics
Brief Summary

The goal of this observational study is to characterize clinical measures and biomarkers of airway disease in adults with primary ciliary dyskinesia (PCD) and in a group of healthy volunteers (HV) to establish normative values. Lung function, mucociliary clearance, radiological findings, and clinical findings will be assessed. Furthermore, quality of life will be assessed using QOL-PCD, a disease specific questionnaire.

Detailed Description

Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disease characterized by progressive upper and lower respiratory tract infections and inflammation caused by impaired mucociliary clearance (MCC). While longitudinal studies of children and adolescents with PCD have informed the early natural history of lung disease, there remains a knowledge gap in disease characteristics and progression in adults. There are no prospective published data evaluating the natural history of airway morbidity and mortality in adults, and little is known about the optimal clinical measures and biomarkers to evaluate disease progression. Cohort studies are needed to understand clinical measures and biomarkers across the lifespan of people with PCD, distinguish disease subtypes, and define endpoint variability. Natural history studies are critical for designing future clinical trials. New therapies have lagged in part due to lack of clear clinical biomarkers for adults.

The overarching goal is to characterize clinical measures and biomarkers of airway disease in adults with PCD. In addition, a subset of these clinical measures and biomarkers will be collected in a group of healthy volunteers (HV) to establish normative values.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
50
Inclusion Criteria
  • PCD diagnosis with confirmation of 2 identified pathogenic genetic variants within 1 of the following ultrastructure variants:
  • DNAI1 ODA defect
  • Other ODA defect
  • IDA - MTD defect
  • RS defect
  • Informed consent
Exclusion Criteria
  • Are a current smoker (e-cigarette, tobacco, or marijuana)
  • Are a former smoker who discontinued smoking <1 year prior to enrollment or has a cumulative 1+ pack-year smoking history
  • Have a recent stable forced expiratory volume in one second (FEV1) <35% predicted
  • Have contraindications for MRI studies (implanted devices/materials; inability to tolerate; claustrophobia or severe anxiety that would preclude MRI/imaging)
  • Have had a significant clinical radiation exposure (as determined by the investigator) within the past 6 months. Potential participants who have had a chest CT within the past 6 months may be eligible to be enrolled and their clinical CT will be utilized as the baseline for this study
  • Are pregnant or breastfeeding
  • Have any comorbidities likely to impact lung function (e.g., complex congenital heart disease, severe scoliosis, diseases involving immune dysregulation, lung transplantation, lung lobectomy, end-stage renal disease, or poor overall health status).

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
PCD CohortMultiple Breath Washout (MBW)The PCD cohort will include individuals who have a genetically confirmed diagnosis of PCD with 2 identified pathogenetic variants within 1 of 4 genetic/ultrastructural variants: * DNAI1 ODA defect * Other ODA defect * IDA-MTD defect, CCDC39 or CCDC40 * Radial Spoke defect
Healthy Volunteer CohortMucociliary Clearance (MCC)The healthy volunteer cohort will include health individuals.
PCD CohortSpirometryThe PCD cohort will include individuals who have a genetically confirmed diagnosis of PCD with 2 identified pathogenetic variants within 1 of 4 genetic/ultrastructural variants: * DNAI1 ODA defect * Other ODA defect * IDA-MTD defect, CCDC39 or CCDC40 * Radial Spoke defect
PCD CohortMucociliary Clearance (MCC)The PCD cohort will include individuals who have a genetically confirmed diagnosis of PCD with 2 identified pathogenetic variants within 1 of 4 genetic/ultrastructural variants: * DNAI1 ODA defect * Other ODA defect * IDA-MTD defect, CCDC39 or CCDC40 * Radial Spoke defect
PCD CohortCT of the chestThe PCD cohort will include individuals who have a genetically confirmed diagnosis of PCD with 2 identified pathogenetic variants within 1 of 4 genetic/ultrastructural variants: * DNAI1 ODA defect * Other ODA defect * IDA-MTD defect, CCDC39 or CCDC40 * Radial Spoke defect
Healthy Volunteer CohortSpirometryThe healthy volunteer cohort will include health individuals.
Healthy Volunteer CohortMRI of the chestThe healthy volunteer cohort will include health individuals.
PCD CohortMRI of the chestThe PCD cohort will include individuals who have a genetically confirmed diagnosis of PCD with 2 identified pathogenetic variants within 1 of 4 genetic/ultrastructural variants: * DNAI1 ODA defect * Other ODA defect * IDA-MTD defect, CCDC39 or CCDC40 * Radial Spoke defect
Primary Outcome Measures
NameTimeMethod
Descriptive AnalysisFrom Baseline Through Week 52

Descriptive statistical methods will be applied to analyze: lung function, measure % predicated (pp) FEV1. Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 52

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

University of North Carolina at Chapel Hill

🇺🇸

Chapel Hill, North Carolina, United States

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