- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00760708
Circulating Adenosine Levels Before and After Intravenous (IV) Persantine
Descripción general del estudio
Estado
Condiciones
Descripción detallada
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.
Tipo de estudio
Inscripción (Actual)
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
Connecticut
-
Farmington, Connecticut, Estados Unidos, 06032
- University of Connecticut Health Center
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Método de muestreo
Población de estudio
Descripción
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%)
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Modelos observacionales: Control de caso
- Perspectivas temporales: Futuro
Cohortes e Intervenciones
Grupo / Cohorte |
---|
undergoing persantine stress test
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
---|---|
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.
Periodo de tiempo: 24 hours
|
24 hours
|
Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
---|---|
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.
Periodo de tiempo: 2 years
|
2 years
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Bruce T Liang, MD, UConn Health
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 02-115-1
- Proposal Number 04156012
- Award NumberW81XWH-05-1-0060
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .