Ignite Creation Date:
2025-12-25 @ 12:22 AM
Ignite Modification Date:
2025-12-25 @ 10:25 PM
Study NCT ID:
NCT03057158
Status:
COMPLETED
Last Update Posted:
2020-09-29
First Post:
2017-02-13
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Genomics and Epigenomics for New Insights in fEmale OAB (GENIE) Study
Sponsor:
Duke University
Organization:
Study Overview
Official Title:
Epigenomics in Insulin Resistance Associated Overactive Bladder.
Status:
COMPLETED
Status Verified Date:
2019-11
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:
GENIE
Brief Summary:
Millions of women suffer from overactive bladder, and the changes in bladder function affect their quality of life. The study team believes that it needs to be better understand why women get overactive bladder in the first place so that better treatments can eventually be offered.
The purpose of this study is to determine why women with insulin resistance are more likely to get overactive bladder. Overactive bladder is a type of bladder control problem that can cause some women to have bladder leakage. This problem is more common in women with diabetes and pre-diabetes, but it isn't known why.
The purpose of this study is to determine why women with insulin resistance are more likely to get overactive bladder. Overactive bladder is a type of bladder control problem that can cause some women to have bladder leakage. This problem is more common in women with diabetes and pre-diabetes, but it isn't known why.
Detailed Description:
The methylation of cytosines in CpG sites can have profound effects on the ability of genes to be transcribed. To clarify and distinguish the specific methylation changes responsible for overactive bladder (OAB) in those with insulin resistance (IR), the investigator will compare three well-characterized groups of women: 1) OAB and IR; 2) IR only (no OAB); and 3) OAB only (no IR). In this proposal the investigator is only studying women since they are more likely to be affected by OAB with incontinence, the investigator wants to study pure cohorts of patients, and because this is the clinical population cared for by the primary investigator. The plan for future investigations is to apply these findings to broader groups to better understand gender and racial differences.
In Specific Aim 1, the investigator will conduct an epigenome-wide association study (EWAS) study, followed by targeted validation studies to determine whether CpG sites throughout the genome are differentially methylated in well-characterized and matched cohorts, while controlling for the effects of insulin-resistance. In Specific Aim 2, the investigator will assess for differential expression of candidate loci in relation to methylation. RNA-sequencing (RNA-seq) will be used to establish differences in the transcriptome between extreme phenotypes of OAB+IR and OAB alone. The investigator will then use quantitative polymerase chain reaction (qPCR) to validate expression differences in all cohorts, and to confirm differences in candidate loci that are confirmed in experiments from Aim 1. The investigator will proceed with bioinformatic pathway analyses to identify the function and interdependence of genes with altered expression and altered methylation profiles. In Specific Aim 3, the investigator will determine whether expression (mRNA and protein) differences in voided urine cells are also exhibited in biopsied bladder mucosa. The investigator will use targeted assays to confirm similar methylation profiles and gene expression in voided cells and bladder biopsies. The investigator will also compare protein expression of candidate loci such as EXOC6, ZFC3H1, RPS6KA2, and SPON2 proteins, if confirmed in other Aims, between cohorts. When the proposed studies have been completed, it is the expectation that the investigator will have functionally characterized the methylation changes that the investigator preliminarily identified in IR associated OAB.
In Specific Aim 1, the investigator will conduct an epigenome-wide association study (EWAS) study, followed by targeted validation studies to determine whether CpG sites throughout the genome are differentially methylated in well-characterized and matched cohorts, while controlling for the effects of insulin-resistance. In Specific Aim 2, the investigator will assess for differential expression of candidate loci in relation to methylation. RNA-sequencing (RNA-seq) will be used to establish differences in the transcriptome between extreme phenotypes of OAB+IR and OAB alone. The investigator will then use quantitative polymerase chain reaction (qPCR) to validate expression differences in all cohorts, and to confirm differences in candidate loci that are confirmed in experiments from Aim 1. The investigator will proceed with bioinformatic pathway analyses to identify the function and interdependence of genes with altered expression and altered methylation profiles. In Specific Aim 3, the investigator will determine whether expression (mRNA and protein) differences in voided urine cells are also exhibited in biopsied bladder mucosa. The investigator will use targeted assays to confirm similar methylation profiles and gene expression in voided cells and bladder biopsies. The investigator will also compare protein expression of candidate loci such as EXOC6, ZFC3H1, RPS6KA2, and SPON2 proteins, if confirmed in other Aims, between cohorts. When the proposed studies have been completed, it is the expectation that the investigator will have functionally characterized the methylation changes that the investigator preliminarily identified in IR associated OAB.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 302-0870 | OTHER_GRANT | NIDDK | View |