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The Phenotyping and Genotyping of Taiwanese Patients With Obstructive Sleep Apnea

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified January 2014 by National Taiwan University Hospital.
Recruitment status was:  Recruiting
Sponsor:
ClinicalTrials.gov Identifier:
NCT02038751
First Posted: January 17, 2014
Last Update Posted: January 17, 2014
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. Read our disclaimer for details.
Information provided by (Responsible Party):
National Taiwan University Hospital
  Purpose

The growing evidence showed that the OSA is a heritable complex genetic disease where the genetic basis contributed the development of OSA and its sequel. The phenotyping of OSA include high level and intermediate level. The former indicates the AHI, and later includes craniofacial morphology, ventilator control, obesity, and sleepiness vulnerability.

Many studies tried to determine the association of candidate genes with OSA through association studies. However, the results were conflicting. We identified 37 candidate genes involved in six biologic pathways of OSA reported in previous literatures, including oxidative phosphorylation, cell signaling, apoptosis, cellular adhesion and motility, cell cycle, and cytokine/chemokine.

To investigate the association between phenotype and genotype of OSA, we conducted this cross-sectional study by recruiting the patients of moderate-severe OSA (index proband) and their first and second-degree family members, and friends and their family members (control family) and using candidate genes reported in the literature and whole genome SNP array for genotype approach.


Condition
Sleep Apnea, Obstructive

Study Type: Observational
Study Design: Observational Model: Family-Based
Time Perspective: Cross-Sectional
Official Title: The Phenotyping and Genotyping of Taiwanese Patients With Obstructive Sleep Apnea

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • Family aggregation of OSA and its phenotype [ Time Frame: within the first half year after enrollment ]
    Phenotypes assessment by PSG, craniofacial image, Hypercapnic ventilatory response testing, psychomotor vigilance task, MSLT, blood biochemistry testing, abdominal MRI, and 24 hr ambulatory BP monitor Family aggregation assessed by family-based study design (1. to compare risk of OSA between index and control proband; 2. to compare risk between index proband with more than one families suffering OSA and without; 3. to calculate inter-generation and intra-generation association index of AHI)

  • Association between phenotype and genotype of OSA [ Time Frame: within the first half year after enrollment ]
    Genotypes assessed by candidate genes identification or whole genome SNP array Phenotypes assessment by PSG, craniofacial image, Hypercapnic ventilatory response testing, psychomotor vigilance task, MSLT, blood biochemistry testing, abdominal MRI, and 24 hr ambulatory BP monitor Association assessed by linkage study and association study


Biospecimen Retention:   Samples With DNA
whole blood and serum

Estimated Enrollment: 360
Study Start Date: January 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
Index proband
moderate to severe OSA (AHI>30 or AHI>15 needing CPAP intervention) age 20-99 y/o
Index family
first-degree, second-degree, or spouse of index proband age >20 y/o
Control proband
friends of index proband, living in the same environment as index proband age > 20 y/o
Control family
first-degree, second-degree, or spouse of control proband age >20 y/o

Detailed Description:

Obstructive sleep apnea (OSA) is characterized with recurrent collapse of upper airway during sleep resulting in hypoxia and sleep fragmentation. Patients of OSA might have symptoms like snoring, non-restorative sleep, witnessed apnea, and excessive daytime sleepiness. Currently, polysomnography is the gold standard for diagnosing OSA and the apnea-hypopnea index (AHI) is the parameters to indicate the severity of OSA. However, AHI poorly correlated with clinical severity of OSA, where the symptoms of patients with the identical AHI could vary from minimal to striking. The sequels of OSA include cardiovascular diseases, metabolic disorders, and neurocognitive dysfunctions. Till now, continuous positive airway pressure (CPAP) is the standard treatment for OSA where it can effectively improve daytime sleepiness, blood pressure, metabolic abnormalities, and quality of life, especially in patients with daytime sleepiness.

The growing evidence showed that the OSA is a heritable complex genetic disease where the genetic basis contributed the development of OSA and its sequel. The phenotyping of OSA include high level and intermediate level. The former indicates the AHI, and later includes craniofacial morphology, ventilator control, obesity, and sleepiness vulnerability. Many studies tried to determine the association of candidate genes with OSA through association studies. However, the results were conflicting. To clarify the influence of genotyping on phenotyping, we reported a Chinese family with congenital central hypoventilation syndrome (CCHS) that had a clinical spectrum ranging from newborn fatality to adulthood. Genetic analysis was used to confirm the presence of the PHOX2B expansion mutation. Moreover, to clarify the association between ACE I/D polymorphisms and OSA, we undertook a meta-analysis on all studies published in this area. It has not demonstrated an association between the ACE I/D polymorphism and OSA susceptibility irrespective of ethnicity, population sample or the presence/absence of co-morbid hypertension.

Nowadays, a couple of studies tried to genome-wide profiled the candidate genes involved in the biologic pathway of OSA. The whole genome scan identified chromosomes 2p 及19p and chromosomes 8q was associated with AHI in Caucasian and African American, respectively, which is independent of BMI. Also, the whole genome SNP array identified candidate genes associated with OSA as C-reactive protein (C-RP) and glial cell line-derived neurotrophic factor (GDNF) in European Americans and rs9526240 within serotonin receptor 2a (HTR2A) in African Americans. We identified 37 candidate genes involved in six biologic pathways of OSA including oxidative phosphorylation, cell signaling, apoptosis, cellular adhesion and motility, cell cycle, and cytokine/chemokine. Furthermore, three models were constructed to predict the sequel and response to 4-week and 12-week CPAP treatment, respectively.

Since the presentations of OSA are different among races, hence database of Taiwanese patients with OSA is urgently needed to clarify molecular mechanisms. Through recruiting the patients of moderate-severe OSA (index proband) and their first and second-degree family members, and friends and their family members (control family) and via candidate genes reported in the literature and whole genome SNP array, this project aims to achieves following goals (1) Investigating the phenotyping and familial aggregation of OSA (2) Investigating the association of genotyping on phenotyping of OSA (3) Investigating the candidate genes and the involved biologic pathways of OSA. The anticipated contributions of the results include (1) Highlighting the promise of patient-tailored management (2) Establishing an invaluable database of phenotyping and genotyping of OSA for future research (3) Promoting production of biotechnology patent and business.

  Eligibility

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.


Ages Eligible for Study:   20 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
moderate to severe OSA from primary care clinic friends and families from recommendation of OSA patients
Criteria

Inclusion Criteria:

  • all participants needing age > 20 y/o
  • Index proband: OSA diagnosed by overnight polysomnography (AHI>30 or AHI>15 needing therapeutic intervention)
  • Index family: first-degree, second-degree relatives, or spouse of index proband
  • Control proband: friends recommended by index proband, who lived in the same environment as index proband
  • Control family: first-degree, second-degree relatives, or spouse of control proband

Exclusion Criteria:

  • Severe CHF, COPD, CKD
  • Psychiatric disorder who can't coordinate to receive evaluation
  • Autoimmune disorders
  • Other sleep disorders
  • Refusing to anticipate or involving other study at the same time
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT02038751


Contacts
Contact: Peilin Lee, M.D, Ph.D. 886-972-651-763 leepeilin@ntu.edu.tw

Locations
Taiwan
Center of sleep disorders, National Taiwan University Hospital Recruiting
Taipei, Taiwan, 100
Contact: Peilin Lee    886-972-651-763    leepeilin@ntu.edu.tw   
Principal Investigator: Peilin Lee, M.D., Ph.D.         
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: Peilin Lee, M.D, Ph.D. Center of sleep disorders, National Taiwan University Hospital
  More Information

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT02038751     History of Changes
Other Study ID Numbers: 201306007RINB
First Submitted: January 15, 2014
First Posted: January 17, 2014
Last Update Posted: January 17, 2014
Last Verified: January 2014

Keywords provided by National Taiwan University Hospital:
Genotyping
Phenotyping
Sleep Apnea
Genetic Association Studies
Phenotype

Additional relevant MeSH terms:
Apnea
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases