Ignite Creation Date:
2024-05-05 @ 6:30 PM
Last Modification Date:
2024-10-26 @ 9:34 AM
Study NCT ID:
NCT00498732
Status:
COMPLETED
Last Update Posted:
2010-12-01
First Post:
2007-07-08
Brief Title:
Dissection of Differentially Expressed Genes and Pathways in Patients With OSAS Before and After CPAP Treatment
Sponsor:
National Taiwan University Hospital
Organization:
National Taiwan University Hospital
Study Overview
Official Title:
Dissection of Differentially Expressed Genes and Pathways in Patients With Obstructive Sleep Apnea Syndrome Before and After CPAP Treatment
Status:
COMPLETED
Status Verified Date:
2010-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Specific Aim
1 To verify the differentially expressed genes and pathways between normal and OSA patients and OSA patients before and after CPAP treatment
Genes with changes in expression of more than two-fold between normal and OSA patients as well as OSA patients before and after CPAP treatment were thought as confirmed and were selected for further validation study
2 To correlate the confirmed genes with the clinical presentations and CPAP effects in another 50 OSAS subjects to validate the altered gene expressions and pathways involved
To investigate the correlation of genes confirmed from RT-PCR identified gene another 50 OSAS subjects are included in the study We analyze the correlation between identified gene and the clinical manifestations and CPAP effect in these 50 OSAS patients
3 To establish a cell model to investigate the differentially expressed genes and the putative biological pathways involved in OSA syndrome
To investigate the functions of genes identified in the first and second year gene of interest we establish a cell model with human monocyte cell line U937 We investigate the function of gene of interest through overexpress or knockdown
Objectives The objectives of this project are to confirm the gene profiled from comparing normal and OSA patients as well as OSA patients before and after CPAP treatment to investigate the correlation between altered gene expression and clinical presentations and CPAP effects of the OSAS and to identify and confirm corresponding pathway This study will enhance our understanding of the individual constitution on widely different clinical characteristics and therapeutic variations All these efforts will also help us to interpret its molecular mechanisms and develop prediction and diagnosis strategies of OSAS The long-term objectives are to develop therapeutic strategy other than CPAP of OSAS
1 To verify the differentially expressed genes and pathways between normal and OSA patients and OSA patients before and after CPAP treatment
Genes with changes in expression of more than two-fold between normal and OSA patients as well as OSA patients before and after CPAP treatment were thought as confirmed and were selected for further validation study
2 To correlate the confirmed genes with the clinical presentations and CPAP effects in another 50 OSAS subjects to validate the altered gene expressions and pathways involved
To investigate the correlation of genes confirmed from RT-PCR identified gene another 50 OSAS subjects are included in the study We analyze the correlation between identified gene and the clinical manifestations and CPAP effect in these 50 OSAS patients
3 To establish a cell model to investigate the differentially expressed genes and the putative biological pathways involved in OSA syndrome
To investigate the functions of genes identified in the first and second year gene of interest we establish a cell model with human monocyte cell line U937 We investigate the function of gene of interest through overexpress or knockdown
Objectives The objectives of this project are to confirm the gene profiled from comparing normal and OSA patients as well as OSA patients before and after CPAP treatment to investigate the correlation between altered gene expression and clinical presentations and CPAP effects of the OSAS and to identify and confirm corresponding pathway This study will enhance our understanding of the individual constitution on widely different clinical characteristics and therapeutic variations All these efforts will also help us to interpret its molecular mechanisms and develop prediction and diagnosis strategies of OSAS The long-term objectives are to develop therapeutic strategy other than CPAP of OSAS
Detailed Description:
Obstructive sleep apnea syndrome OSAS is characterized with recurrent collapse of upper airway during sleep and resulted in hypoxia and sleep fragmentation which resulted in cardiovascular diseases metabolic disorders and neurocognitive dysfunctions The cardiovascular complications attributed to OSAS included hypertension coronary artery disease heart failure and stroke The mechanisms responsible for developments of cardiovascular sequelae included repeated episodes of hypoxia and hypercapnia exaggerated negative intrathoracic pressure and bursts of sympathetic activity provoking surges in blood pressure and heart rate Increase of inflammatory mediators which included C-reactive protein oxidative stress adhesion molecules vascular endothelial growth factor and proinflammatory cytokines were thought to involve in the developments of cardiovascular diseases in patients with OSAS
To clarify the exact mechanisms of OSAS and the linkage to cardiovascular complications in our previous study we used oligo microarray to genome-wide profile the gene expression patterns in OSAS patients and the changes of gene expressions before and after four-week CPAP treatment The oligo-microarray data were processed with CRSD database and two-way hierarchical clustering method The results showed the gene expression patterns were different between control subjects and OSA patients and CPAP treatment also altered the gene expression patterns Totally 27 genes and four pathways were identified as target genes and pathways from comparing the gene pattern changes before and after CPAP treatment which included apoptosis oxidative phosphorylation cell adhesion and activation and metabolism To continue analyzing the gene pattern changes before and after CPAP treatment we propose this three-year project to achieve the following goals 1 To verify the differentially expressed genes and pathways between normal and OSA patients and OSA patients before and after CPAP treatment 2 To correlate the confirmed genes with the clinical presentations and CPAP effects in another 50 OSAS subjects to validate the altered gene expressions and pathways involved 3 To establish a cell model to investigate the differentially expressed genes and the putative biological pathways involved in OSA syndrome The information obtained by this approach is very useful to understand the pathogenic mechanism of OSA that leads to systemic complications and further therapeutic intervention may therefore be possible
To clarify the exact mechanisms of OSAS and the linkage to cardiovascular complications in our previous study we used oligo microarray to genome-wide profile the gene expression patterns in OSAS patients and the changes of gene expressions before and after four-week CPAP treatment The oligo-microarray data were processed with CRSD database and two-way hierarchical clustering method The results showed the gene expression patterns were different between control subjects and OSA patients and CPAP treatment also altered the gene expression patterns Totally 27 genes and four pathways were identified as target genes and pathways from comparing the gene pattern changes before and after CPAP treatment which included apoptosis oxidative phosphorylation cell adhesion and activation and metabolism To continue analyzing the gene pattern changes before and after CPAP treatment we propose this three-year project to achieve the following goals 1 To verify the differentially expressed genes and pathways between normal and OSA patients and OSA patients before and after CPAP treatment 2 To correlate the confirmed genes with the clinical presentations and CPAP effects in another 50 OSAS subjects to validate the altered gene expressions and pathways involved 3 To establish a cell model to investigate the differentially expressed genes and the putative biological pathways involved in OSA syndrome The information obtained by this approach is very useful to understand the pathogenic mechanism of OSA that leads to systemic complications and further therapeutic intervention may therefore be possible
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None