Characterizing the Upper Airway Manifestations in Primary Ciliary Dyskinesia and Primary Immunodeficiencies

Completed

Conditions studied: Primary Ciliary Dyskinesia, Kartagener Syndrome, Primary Immune Deficiency

In brief

Though common, morbidities related to upper airway disease in primary ciliary dyskinesia (PCD) and primary immunodeficiencies (PID) have not been fully characterized. These conditions can be difficult to distinguish due to their overlapping phenotypes. The sinonasal and middle ear features are often identified as most problematic by patients and their families, and optimal, highly effective treatment regimens have not been established. The main objective of this project is to characterize and compare the upper airway phenotypes in individuals with confirmed diagnosis of PCD and PID, and to collect critical data to inform the design of future clinical trials of treatment of the upper airway diseases. The investigators anticipate that these investigations will discern the clinical, anatomical, and pathophysiological phenotypes of paranasal sinus disease in PCD and PID, identifying disease endpoints and biomarkers that differentiate these two overlapping disorders. Findings from these studies will also enhance our understanding of middle ear disease and associated hearing loss in a cross-sectional cohort of patients with PCD and PID. Ultimately, the long-term goal of our Consortium is to elucidate underlying phenotypes and genotypes of these diseases, potentially leading to novel therapeutics that will improve the lives of affected individuals. Given the COVID pandemic, certain procedures will have the option to be converted to telehealth visits to ensure compliance with local guidelines and participant safety.

Key facts

Study ID

NCT04919018

Run by

University of North Carolina, Chapel Hill

People needed

159

Starts

2021-06-09

Expected to finish

2025-07-23

Last updated by the study team

2025-08-21

Who can join

Age: 5 and older, up to 45. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Overall inclusion criteria for PCD and PID:
• Ages ≥ 5-45 years.
• Informed consent, and assent from minors.
• Inclusion Criteria for PCD:
• Clinical features consistent with PCD plus
• At least one diagnostic test consistent with PCD:
• Biallelic pathogenic variants in PCD-associated genes identified by genetic panel testing including deletion/duplication analysis.
• Ciliary ultrastructural defect by transmission electron microscopy known to be disease causing, including outer dynein arm defects, outer and inner dynein arm defects, or inner dynein arm defects with microtubular disorganization.
• Inclusion Criteria for PID:
• A clinical diagnosis of PID known to be associated with an increased risk of infections, as defined by the European Society of Immunodeficiencies (ESID) registry, AND a genetic confirmation with a known or likely pathogenic variant.
• OR a diagnosis of a common variable immunodeficiency (CVID) as defined by the ESID registry:
• a. At least one of the following:
• i. Increased susceptibility to infection
• ii. Autoimmune manifestations
• iii. Granulomatous disease
• iv. Unexplained polyclonal lymphoproliferation
• v. Affected family member with antibody deficiency
• b. AND marked decrease of IgG and IgA with or without low IgM levels
• c. AND at least one of the following:
• i. Poor antibody response to vaccines (and/or absent isohemagglutinins)
• ii. Low switched memory B cells (<70 percent of age-related normal value)
• d. AND secondary causes of hypogammaglobulinemia have been excluded (e.g., infection, protein loss, medication, malignancy)
• e. AND diagnosis established after the 4th year of life
• f. AND no evidence of profound T cell deficiency

You may not qualify if…

• Inability to undergo study procedures
• Reported increased respiratory symptoms within 3 weeks before the scheduled visit
• Congenital craniofacial abnormalities (cleft lip and/or palate, hemifacial microsomia) that may result in otologic or sinus disease
• Congenital hearing loss
• Diagnosis of Trisomy 21, Kabuki syndrome, DiGeorge anomaly or syndrome, 22q11 deletion syndrome, or CHARGE syndrome
• History of intranasal illicit drug use (i.e. cocaine) or intranasal abuse of over the counter or prescription drugs (i.e. oxycodone, acetaminophen, etc.)
• Pregnancy
• Known selective IgA deficiency, specific antibody deficiency (SPAD), selective IgG subclass deficiency, selective IgM deficiency, mannose-binding lectin deficiency, as well as inborn errors of immunity (IEIs) which are not known to be associated with an increased risk of infections (e.g. autoinflammatory syndromes; unclassified disorders of immune dysregulation)
• Medical condition that is known to cause secondary immunodeficiency, including human immunodeficiency virus (HIV) infection, acquired immunodeficiency syndrome (AIDS), and/or active malignancy
• Patients ever having received gene therapy, hematopoietic stem cell transplant, solid organ transplant, or thymus transplant
• Treatment with targeted immune modulators or immune modifiers
• Treatment with chronic systemic steroids

Where it is running

• Washington University in St. Louis — St Louis, Missouri, United States
• University of North Carolina at Chapel Hill — Chapel Hill, North Carolina, United States
• The Hospital for Sick Children — Toronto, Ontario, Canada
• McGill University — Montreal, Quebec, Canada

Full record on ClinicalTrials.gov

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