- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT00760708
Circulating Adenosine Levels Before and After Intravenous (IV) Persantine
Studieöversikt
Status
Betingelser
Detaljerad beskrivning
Objectives:
The overall goal of this proposal is to develop methods to achieve heart and vascular protection from ischemia and thus improve soldier's performance in adverse environment. The major hypothesis is that new approach and method can be developed to enhance resistance to stress-induced circulatory insufficiency and myocardial ischemia. The goals here are to determine whether a decreased adenosine transporter function is associated with a reduced physiological responsiveness to the vasculo-protective drug persantine using two in vitro endpoints: the ability of persantine 1) to inhibit platelet aggregation and 2) to inhibit [3H] uridine uptake. Both are endpoints that indicate physiological responsiveness. Both relate directly to the cardiovascular protective effects of , that is, persantine the availability of extracellular adenosine level and the anti-platelet property. Specifically, the relationship between circulating adenosine increase to persantine in vivo and blockade of radio-labeled uridine uptake by erythrocytes and of platelet aggregation by the drug in vitro will be determined. These investigations will recruit subjects undergoing persantine stress testing in the Nuclear Cardiology Laboratory.
Scientific Background and Significance:
Development of methods to protect from skeletal and cardiovascular insufficiency is the main objective of the current research. Adenosine is a potent cyto-protective hormone released during ischemia. The goal of this clinical research project are to test the presence of genetic polymorphisms in the adenosine transporter gene and to determine whether it is associated with an altered persantine responsiveness. The hypothesis is that some or all of these polymorphisms are associated with a decreased responsiveness to persantine and that increasing the dose of persantine will overcome the relative non-response.
Specific Evaluations:
-Persantine Administration: Persantine will be administered after baseline evaluation with intravenous dose (0.56 mg/kg) over 5 minutes.
-Adenosine levels: Adenosine levels will be measured at baseline, and 2 minutes after the persantine dose. We have recently modified and adapted a method to measure nanomolar concentration of adenosine in human blood.
-Adenosine transporter function: The transporter function will be determined by the ability of persantine to inhibit erythrocyte uptake of radio-labeled uridine in vitro.
- Anti-platelet effect of persantine: The platelet aggregation response to persantine will be determined via whole blood aggregometry in vitro where the ex vivo platelet response to the drug can be quantified.
Preliminary Studies:
Preliminary data showed that two non-synonymous single nucleotide polymorphisms occurring at a frequency of 3-4% exist in the persantine-binding regions of the adenosine transporter gene. The goal of the present study is to determine the functional significance of these polymorphisms by testing the association of these polymorphisms with the ability of persantine to inhibit uridine (uridine uses the same transporter) uptake and platelet aggregation. These represent the in vitro functional endpoints in the subjects with the polymorphism. The investigators will also study the association of these polymorphisms with any clinical characteristics such as the incidence of MI, acute coronary syndrome, coronary bypass or stenting procedures. Since this is NOT an interventional study, these are not considered clinical outcomes or endpoints in the traditional sense when an intervention is carried out. These are considered clinical characteristics or phenotypes that associate with the genotype of polymorphisms. Primary and secondary outcomes and endpoints: The goal of the present study is to determine the functional significance of these polymorphisms by testing the association of these polymorphisms with the ability of persantine to inhibit uridine (uridine uses the same transporter) uptake and platelet aggregation. These represent the in vitro functional endpoints in the subjects with the polymorphism. The investigators will also study the association of these polymorphisms with any clinical characteristics such as the incidence of MI, acute coronary syndrome, coronary bypass or stenting procedures. Since this is NOT an interventional study, these are not considered clinical outcomes or endpoints in the traditional sense when an intervention is carried out. These are considered clinical characteristics or phenotypes that associate with the genotype of polymorphisms.
Studietyp
Inskrivning (Faktisk)
Kontakter och platser
Studieorter
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-
Connecticut
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Farmington, Connecticut, Förenta staterna, 06032
- University of Connecticut Health Center
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-
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Testmetod
Studera befolkning
Beskrivning
Inclusion Criteria:
- Subjects with or without coronary artery disease undergoing a Persantine nuclear stress test
Exclusion Criteria:
- Oral persantine use within 24 hours
- Second or third degree AV block, or sick sinus syndrome without a functioning pacemaker
- Active asthma or bronchospasm
- Those with end-stage liver disease such as cirrhosis or active hepatitis such as > 5 fold liver enzyme elevation will not be included
- Anemia (Hct < 30)
- Myocardial infarction within 30 days
- Severe left ventricular dysfunction (EF < 30%)
Studieplan
Hur är studien utformad?
Designdetaljer
- Observationsmodeller: Case-Control
- Tidsperspektiv: Blivande
Kohorter och interventioner
Grupp / Kohort |
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undergoing persantine stress test
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Tidsram |
---|---|
To determine functional significance and association of these polymorphisms with the ability of persantine to inhibit uridine (uridine uses the same transporter) uptake and platelet aggregation.
Tidsram: 24 hours
|
24 hours
|
Sekundära resultatmått
Resultatmått |
Tidsram |
---|---|
Investigators will study the association of these polymorphisms with any clinical characteristics such as the incidence of MI, acute coronary syndrome, coronary bypass or stenting procedures. These clinical outcomes are considered secondary endpoints.
Tidsram: 2 years
|
2 years
|
Samarbetspartners och utredare
Sponsor
Samarbetspartners
Utredare
- Huvudutredare: Bruce T Liang, MD, Uconn Health
Studieavstämningsdatum
Studera stora datum
Studiestart
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- 02-115-1
- Proposal Number 04156012
- Award NumberW81XWH-05-1-0060
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