Effect of Gene Variants on Dopamine Receptor Natriuretic Responses
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|ClinicalTrials.gov Identifier: NCT00592150|
Recruitment Status : Unknown
Verified January 2013 by Robert M. Carey, MD, University of Virginia.
Recruitment status was: Active, not recruiting
First Posted : January 11, 2008
Last Update Posted : January 23, 2013
Hypothesis to be tested: Dopamine D1-like receptor-induced natriuresis is impaired in humans with G protein-related kinase 4 gene variants.
Our research group has discovered a D1 receptor/adenylyl cyclase coupling defect in renal PTCs from subjects with essential hypertension. We have found increased GRK-4 activity in renal PTCs in human essential hypertension due to activating variants of GRK-4, an effect that was reproduced in a transfected cell model. Preventing the translation of GRK-4 normalized the coupling of the D1 receptor to adenylyl cyclase in hypertension. Gene variants of GRK-4 cause a ligand-independent serine-phosphorylation of the D1 receptor, resulting in its uncoupling from the G-protein/effector complex. The desensitization of the D1 receptor in the renal PTC is hypothesized to be the cause of the compromised natriuretic effect of DA that eventually leads to Na+ retention and hypertension. The primary objective of this protocol is to demonstrate that natriuresis engendered by D1-like receptor activation with fenoldopam is blunted in subjects with 3 or more SNPs of GRK-4 compared with responses in subjects with 0-2 SNPs.
|Condition or disease||Intervention/treatment||Phase|
|Hypertension||Drug: fenoldopam Drug: Placebo||Phase 1|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||44 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Effect of Gene Variants on Dopamine Receptor Natriuretic Responses (RMC033)|
|Study Start Date :||June 2007|
|Actual Primary Completion Date :||March 2008|
|Estimated Study Completion Date :||June 2013|
The fenoldopam infusion rate will be 0.05 μg/kg/min for 3 hours
Placebo Comparator: 2
Placebo infusion for 3 hours
- Urine sodium excretion [ Time Frame: 7 days ]
- gene dose effect of GPK-4 on fenoldopam induced natriuresis [ Time Frame: 7 days ]
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): NCT00592150
|United States, Virginia|
|University of Virginia|
|Charlottesville, Virginia, United States, 22903|
|Principal Investigator:||Robert M Carey, MD||University of Virginia|