Ignite Creation Date:
2024-05-05 @ 1:26 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00005757
Status:
COMPLETED
Last Update Posted:
2016-11-28
First Post:
2000-05-25
Brief Title:
Racial Variation in ACE--Genetic and Physiologic Bases
Sponsor:
Vanderbilt University
Organization:
Vanderbilt University
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2016-11
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:
To determine whether differences in the activity of the renin-angiotensin and bradykinin systems are involved in the pathogenesis of blood pressure variation in African Americans
Detailed Description:
BACKGROUND
Each year more than 40000 new patients require treatment for end stage renal disease a condition which is 4-fold higher among African Americans than Caucasians Trials of angiotensin converting enzyme inhibitors ACEIs in Caucasians support a role of the renin-angiotensin system in the pathogenesis of glomerulosclerosis Yet despite the high prevalence of nephropathy among African Americans Blacks have been under-represented in studies in ACEIs Data from our laboratory suggest that the renal effects of ACEI may differ in African Americans African Americans are resistant to the anti-hypertensive effects of ACEI and thus may be resistant to the renoprotective effects as well The ACE deletion allele a variant associated with increased ACE activity and progression of renal diseases is increased in frequency in African Americans while the frequency of the Ang AT1 receptor C allele a variant associated with antihypertensive responsiveness to ACEI is decreased Moreover African Americans exhibit decreased sensitivity to Ang I and increased sensitivity to bradykinin Taken together these data suggest the hypothesis that ACE activity is increased in African Americans leading to decreased bradykinin levels and receptor sensitization and increased tissue Ang II and receptor desensitization
DESIGN NARRATIVE
The study tests the hypothesis that ACE activity is increased in African Americans leading to decreased bradykinin levels and receptor sensitization and increased tissue Ang II and receptor desensitization The effects of race hypertension and ACE insertiondeletion genotype on ACE activity will be determined as measured by the pressor and renal vasoconstrictor responses to Ang I and Ang II and the vasodilator response to bradykinin Specific bradykinin and angiotensin receptor antagonists will be used to determine the relative contribution of increased bradykinin and decreased angiotensin II to the renal hemodynamic effects of ACEIs in African Americans and Caucasians
Each year more than 40000 new patients require treatment for end stage renal disease a condition which is 4-fold higher among African Americans than Caucasians Trials of angiotensin converting enzyme inhibitors ACEIs in Caucasians support a role of the renin-angiotensin system in the pathogenesis of glomerulosclerosis Yet despite the high prevalence of nephropathy among African Americans Blacks have been under-represented in studies in ACEIs Data from our laboratory suggest that the renal effects of ACEI may differ in African Americans African Americans are resistant to the anti-hypertensive effects of ACEI and thus may be resistant to the renoprotective effects as well The ACE deletion allele a variant associated with increased ACE activity and progression of renal diseases is increased in frequency in African Americans while the frequency of the Ang AT1 receptor C allele a variant associated with antihypertensive responsiveness to ACEI is decreased Moreover African Americans exhibit decreased sensitivity to Ang I and increased sensitivity to bradykinin Taken together these data suggest the hypothesis that ACE activity is increased in African Americans leading to decreased bradykinin levels and receptor sensitization and increased tissue Ang II and receptor desensitization
DESIGN NARRATIVE
The study tests the hypothesis that ACE activity is increased in African Americans leading to decreased bradykinin levels and receptor sensitization and increased tissue Ang II and receptor desensitization The effects of race hypertension and ACE insertiondeletion genotype on ACE activity will be determined as measured by the pressor and renal vasoconstrictor responses to Ang I and Ang II and the vasodilator response to bradykinin Specific bradykinin and angiotensin receptor antagonists will be used to determine the relative contribution of increased bradykinin and decreased angiotensin II to the renal hemodynamic effects of ACEIs in African Americans and Caucasians
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R29HL056963 | NIH | None | httpsreporternihgovquickSearchR29HL056963 |