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PCD New Gene Discovery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03801395
Recruitment Status : Recruiting
First Posted : January 11, 2019
Last Update Posted : January 16, 2019
Information provided by (Responsible Party):
Michael O'Connor, Vanderbilt University Medical Center

Brief Summary:
This is a new gene discovery program for individuals with PCD who do not have a specific genetic etiology identified. Research procedures involve a single blood draw from the affected individual and from unaffected family members in an effort to identify new genetic targets.

Condition or disease Intervention/treatment
Primary Ciliary Dyskinesia Other: There is no intervention

Detailed Description:

The objective of this study is to better define how the genes that cause primary ciliary dyskinesia (PCD) are related to the clinical symptoms of individuals with PCD. PCD is a rare disease that affects the function of motor cilia throughout the body. This results in a variety of clinical symptoms, but chief among them are a chronic wet cough, recurrent sinusitis, and frequent pneumonia. These clinical symptoms can result in further structural lung disease, including bronchiectasis, with eventual worsening of lung function. The treatment for this condition largely focuses on augmenting airway clearance and appropriate use of antimicrobial therapies, in conjunction with monitoring for evidence of pulmonary impairment. Thus, it is important to identify and diagnose individuals with PCD early in life.

Making a diagnosis of PCD can be difficult as their is some overlap of the clinical symptoms with other conditions and there are limitation in the current diagnostic testing modalities. Historically, the diagnosis has been made by identification of structural abnormalities in cilia by electron microscopy (ciliary biopsy). However, this testing has limitations secondary to the somewhat invasive nature of the procedures and often inconclusive results secondary to sampling challenges (getting enough cilia). Furthermore, a normal ciliary biopsy result does not rule-out PCD as it is now known that there are individuals with PCD who have ciliary dysfunction secondary to ciliary abnormalities that are not routinely identified on standard electron micrograph. Genetic testing for PCD is available, but current testing only accounts for about 60-65% of the PCD population. Thus normal results in this regard do not rule-out PCD either. Nasal nitric oxide (nNO) testing is an emerging research-based testing that is being used more frequently to identify individuals with PCD. More specifically, it has been frequently observed that individuals with PCD have low levels of nitric oxide in their sinus cavities. Measuring a low level of nitric oxide of multiple different occasions has proven to have diagnostic utility in an individual with a clinical symptom history consistent with PCD. While nNO testing is helpful for identifying individuals likely to have PCD, this testing does not give further information as to reason for ciliary dysfunction. Current testing availability has resulted in a group of individuals who are being managed as "probable PCD" which is defined by having clinical symptoms consistent with PCD (such as year-round wet cough and rhinitis) at least two separate positive (low value) nNO testing results, but negative PCD genetics and a non diagnostic ciliary biopsy. While these individuals are often managed the same as other individuals with more defined PCD, including augmentation of airway clearance therapies, in order for more specific care to be applied in the future it is important to better define the ciliary structural reason for their clinical symptoms. This could also be described as needing to better understand the genotype-phenotype of all individuals with PCD.

This investigation seeks to better define the genotypic-phenotypic relationship of individuals by initially focusing on new gene discovery in individuals with probable PCD. More specifically, through whole-exome evaluation of individuals with probable PCD and unaffected first-degree relatives, we will focus on identifying new mutations in ciliary structural proteins and other related pulmonary genes. New gene targets will then be further studied through analysis of ciliary structure and function.

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Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Family-Based
Time Perspective: Prospective
Official Title: Primary Ciliary Dyskinesia New Gene Discovery to Improve Diagnostics and Clinical Care
Actual Study Start Date : January 7, 2019
Estimated Primary Completion Date : July 1, 2019
Estimated Study Completion Date : January 1, 2020

Intervention Details:
  • Other: There is no intervention
    No intervention

Primary Outcome Measures :
  1. DNA analysis [ Time Frame: 6 months ]
    Blood will be obtained for DNA analysis and identification of new PCD genes. Genetic analysis will be done by whole exome sequencing

Biospecimen Retention:   Samples With DNA
Blood samples will be obtained for DNA analysis

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   up to 90 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Individuals with confirmed or suspected PCD and their unaffected family members

Inclusion Criteria:

  • • Age 0-90 years

    • Confirmed diagnosis of PCD by either ciliary ultrastructure abnormality or two known disease-causing alleles in a known PCD gene OR individuals with clinical suspicion of PCD without a confirmatory test (genetics or ciliary biopsy) as defined by: low nasal nitric oxide testing (<77nl/min) on two separate occasions at least two months apart or compatible clinical phenotype, but unable to do nasal nitric oxide testing secondary to age or other factors OR relative of one of the previously defined individuals with PCD
    • Ability to provide informed consent or consent of parent/guardian and assent for minors

Exclusion Criteria:

  • • Inability to understand the requirements of the study or be unwilling to provide written informed consent (as evidenced by signature on an informed consent document approved by the IRB) OR inability of parent/guardian to understand the requirements of the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03801395

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Contact: Michael G O'Connor, MD 615.343.7617

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United States, Tennessee
Vanderbilt Children's hospital Recruiting
Nashville, Tennessee, United States, 37232
Contact: Michael O'Connor, MD         
Sponsors and Collaborators
Vanderbilt University Medical Center

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Responsible Party: Michael O'Connor, Assistant Professor, Vanderbilt University Medical Center Identifier: NCT03801395     History of Changes
Other Study ID Numbers: 182074
First Posted: January 11, 2019    Key Record Dates
Last Update Posted: January 16, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Ciliary Motility Disorders
Kartagener Syndrome
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Abnormalities, Multiple
Congenital Abnormalities
Genetic Diseases, Inborn
Bronchial Diseases
Respiratory System Abnormalities
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Situs Inversus