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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04702243
Other study ID # 20-0508
Secondary ID 5U54HL096458-17
Status Recruiting
Phase
First received
Last updated
Start date December 1, 2020
Est. completion date July 31, 2024

Study information

Verified date April 2024
Source University of North Carolina, Chapel Hill
Contact Kelli Sullivan, MPH
Phone 919-962-9786
Email kelli_sullivan@med.unc.edu
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

The investigators will utilize a systematic approach for the diagnostic evaluation of patients to identify characteristics which may distinguish between Primary Immunodeficiency (PID) disorders versus Primary Ciliary Dyskinesia (PCD).


Description:

This protocol utilizes a cross-sectional study design. Over a 5-year period, the investigators will enroll patients who have clinical and lab features characteristic of a PID disorder or PCD, but do not have a confirmed genetic diagnosis. Innovative, standardized methods (SOPs) will be utilized, including ciliary ultrastructural analyses by transmission electron microscopy (TEM), as pertinent. Measures of nasal nitric oxide (nNO) will be performed in all subjects to allow comparisons of nNO values in PID vs. PCD. Patients with high likelihood of a PID disorder or a high likelihood of PCD will initially undergo research genetic testing on a commercial approved panel for PID disorders or a panel of at least 37 PCD genes. All subjects who do not have a genetic diagnosis from the test panels will undergo whole exome sequencing (WES) to search for novel genetic etiologies for PID or PCD.


Recruitment information / eligibility

Status Recruiting
Enrollment 1500
Est. completion date July 31, 2024
Est. primary completion date July 31, 2024
Accepts healthy volunteers No
Gender All
Age group 5 Years to 45 Years
Eligibility Pediatric subjects (aged 5-17 years): Inclusion criteria include the major criterion (bronchiectasis in > 1 lobe on current or chest CT in previous 24 months, if available for review), plus one minor criterion, or two minor criteria, if bronchiectasis is not present, (including at least 1 "lung" minor criteria). Adult subjects (aged 18-45 years): Inclusion criteria include the major criteria (bronchiectasis in > 1 lobe on current or chest CT in previous 36 months, if available for review), plus one minor criterion, or three minor criteria, if bronchiectasis is not present, (including at least 1 "lung" minor criteria). Inclusion Criteria: General Criteria - Age 5-45 years - Male and Female Subjects - All races and ethnicities Major Clinical Criteria - Bronchiectasis in > 1 lobe Minor Clinical Criteria, Lung - Neonatal respiratory distress (in term neonates with O2 requirement) - Chronic wet cough (year-round for at least 12 months) - Recurrent episodes of bacterial bronchitis - Recurrent pneumonia (confirmed on chest x-ray) - Respiratory non-tuberculous mycobacteria (NTM) (documented respiratory NTM culture) Minor Clinical Criteria, Other - Chronic nasal congestion - Recurrent/chronic paranasal sinusitis - Ongoing middle-ear disease and/or tympanostomy tube placement at age = 4 years - Organ laterality defect - Low nasal nitric oxide (< 77 nL/min) (by plateau measurement) - Confirmed family history of PID or PCD Exclusion Criteria: - Anyone who has a confirmed genetic diagnosis of PCD or PID - Cystic Fibrosis - Alpha-antitrypsin deficiency in adults (18 years and older) - Congenital upper or lower airway anomalies - Post-lung or heart transplant, or other conditions requiring immunosuppression therapy - Other confounding features, such as lung disease due to prematurity (born < 28 weeks gestation) or HIV - Neurological compromise and evidence of recurrent aspiration - Conditions known to be commonly associated with bronchiectasis, such as prior mycobacterium tuberculosis - Have not had standard clinical evaluation to address other potential causes of chronic oto-sino- pulmonary disease, particularly cystic fibrosis, aspiration or airway anatomic abnormalities.

Study Design


Intervention

Diagnostic Test:
Genetic Testing for PCD or PID
Patients with high likelihood of a PID disorder or a high likelihood of PCD will initially undergo research genetic testing on a commercial approved panel for PID disorders or a panel of at least 37 PCD genes.
Other:
Unaffected Family Member Genetic Testing
Unaffected family members will undergo genetic testing if genetic findings are identified in their affected family member.

Locations

Country Name City State
Canada McGill University Montréal Quebec
Canada The Hospital for Sick Children Toronto Ontario
United States Children's Hospital Colorado Aurora Colorado
United States National Heart, Lung and Blood Institute Bethesda Maryland
United States University of North Carolina at Chapel Hill Chapel Hill North Carolina
United States Stanford University Palo Alto California
United States Washington University in St. Louis Saint Louis Missouri
United States Seattle Children's Hospital Seattle Washington

Sponsors (9)

Lead Sponsor Collaborator
University of North Carolina, Chapel Hill Children's Hospital Colorado, Children's Hospital Medical Center, Cincinnati, McGill University, National Heart, Lung, and Blood Institute (NHLBI), Seattle Children's Hospital, Stanford University, The Hospital for Sick Children, Washington University School of Medicine

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Participants with a Confirmed Diagnosis of PCD or PID A commercial genetic panel will be used to test for disease causing mutation in PCD or PID. If the commercial panel does not yield positive results, WES research testing will be used to identify disease causing mutations in PCD and PID in order to confirm the diagnosis. Up to approximately 4 years
Primary Prevalence of Neonatal Respiratory Distress Seen in PCD and PID Medical records will be reviewed to denote presence or absence of neonatal respiratory distress (occurs at birth). During a single 6-hour visit
Primary Prevalence of the Onset of Chronic Nasal Congestion Before Six Months of Age Seen in PCD and PID Medical records will be reviewed to denote presence or absence of the onset of chronic nasal congestion before age 6 months. During a single 6-hour visit
Primary Prevalence of the Onset of Daily Wet Cough Before Six Months of Age Seen in PCD and PID Medical records will be reviewed to denote presence or absence of the onset of daily wet cough before age 6 months. During a single 6-hour visit
Primary Prevalence of Laterality Defects Seen in PCD and PID Medical records will be reviewed to denote presence or absence of laterality defects (situs inversus/heterotaxy). During a single 6-hour visit
Primary Prevalence of Chronic/Recurrent Sinus Disease Seen in PCD and PID Medical records will be reviewed to denote presence or absence of chronic/recurrent sinus disease. During a single 6-hour visit
Primary Prevalence of Chronic/Recurrent Middle Ear Disease Seen in PCD and PID Medical records will be reviewed to denote presence or absence of chronic/recurrent middle ear disease. During a single 6-hour visit
Primary Prevalence of Recurrent Pneumonia/Sepsis Seen in PCD and PID Medical records will be reviewed to denote to denote presence or absence of recurrent pneumonia/sepsis (that is not bronchiectasis). During a single 6-hour visit
Primary Prevalence of Skin Infections/Abscesses Seen in PCD and PID Medical records will be reviewed to denote to denote presence or absence of skin infections/abscesses. During a single 6-hour visit
Primary Prevalence of Abnormal Nasal Nitric Oxide Values Seen in PCD and PID Nasal nitric oxide will be measured to determine the number of subjects who have an abnormal value, utilizing a cut-off of 77 nl/min. During a single 6-hour visit
Primary Prevalence of Abnormal Immunoglobulin G Values Seen in PCD and PID Immunoglobulin G will be measured to determine the number of subjects who have an abnormal value, utilizing the local laboratory age-defined cut-off ranges (United States: mg/dL; Canada: g/L). During a single 6-hour visit
Primary Prevalence of Abnormal Lymphocyte Markers Seen in PCD and PID (Laboratory Tests) Lymphocyte Markers will be measured to determine the number of subjects who have an abnormal value, utilizing the local laboratory age-defined cut-off ranges (% of lymphocytes). During a single 6-hour visit
Primary Mean FEV1 Percent Predicted Values in PCD and PID Forced expired volume in 1 second (FEV1) will be assessed by percentage of the predicted value (0-100%). During a single 6-hour visit
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