Understanding upper airway issues in primary ciliary dyskinesia and primary immunodeficiencies

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

This study is trying to understand the upper airway problems in people with primary ciliary dyskinesia and primary immunodeficiencies to help improve future treatments.

Quick facts

• Study type: Observational
• Enrollment: 200 (estimated)
• Ages: 5 Years to 45 Years
• Sex: All
• Sponsor: University of North Carolina, Chapel Hill (Academic / other)
• Locations: 4 sites (Saint Louis, Missouri and 3 other locations)
• Trial ID: NCT04919018 on ClinicalTrials.gov

What this trial studies

This observational study aims to characterize and compare the upper airway manifestations in individuals diagnosed with primary ciliary dyskinesia (PCD) and primary immunodeficiencies (PID). Approximately 200 participants will undergo a comprehensive evaluation, including medical history, physical exams, quality of life questionnaires, and various diagnostic tests such as nasal endoscopy and sinus CT scans. The goal is to identify distinguishing clinical and anatomical features that can inform future treatment trials for these overlapping conditions.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 5-45 years with a confirmed diagnosis of either primary ciliary dyskinesia or primary immunodeficiency.

Not a fit: Patients outside the age range of 5-45 years or those without a confirmed diagnosis of PCD or PID may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to better understanding and management of upper airway diseases in patients with PCD and PID.

How similar studies have performed: While there have been studies on PCD and PID separately, this approach of directly comparing upper airway manifestations in both conditions is relatively novel.

Eligibility criteria

Inclusion Criteria:

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:

  1. Biallelic pathogenic variants in PCD-associated genes identified by genetic panel testing including deletion/duplication analysis.
  2. 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

Exclusion Criteria:

* 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 this trial is running

Saint Louis, Missouri and 3 other locations

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

Study contacts

• Principal investigator: Stephanie Davis, MD — University of North Carolina, Chapel Hill
• Study coordinator: Kelli Sullivan

Conditions Primary Ciliary Dyskinesia; Kartagener Syndrome; Primary Immune Deficiency