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Circulating Adenosine Levels Before and After Intravenous (IV) Persantine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00760708
Recruitment Status : Terminated (Persantine is no longer being used at UCHC for pharmacological stress testing)
First Posted : September 26, 2008
Last Update Posted : May 14, 2019
Sponsor:
Collaborator:
United States Department of Defense
Information provided by (Responsible Party):
Bruce Liang, UConn Health

Tracking Information
First Submitted Date September 24, 2008
First Posted Date September 26, 2008
Last Update Posted Date May 14, 2019
Study Start Date September 2005
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: October 7, 2008)
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. [ Time Frame: 24 hours ]
Original Primary Outcome Measures
 (submitted: September 25, 2008)
To determine functional significance and association of these polymorphisms with the ability of dipyridamole to inhibit uridine (uridine uses the same transporter) uptake and platelet aggregation. [ Time Frame: 24 hours ]
Change History Complete list of historical versions of study NCT00760708 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: December 14, 2010)
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. [ Time Frame: 2 years ]
Original Secondary Outcome Measures
 (submitted: September 25, 2008)
We 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. These clinical outcomes are considered secondary endpoints. [ Time Frame: 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Circulating Adenosine Levels Before and After Intravenous (IV) Persantine
Official Title Circulating Adenosine Levels Before and After Intravenous (IV) Persantine
Brief Summary Persantine is a drug that is routinely used to determine blood flow to the heart in the diagnosis of coronary heart disease. Persantine causes an increase in the adenosine level in the blood. Adenosine is a naturally occurring substance in the body that can increase blood flow. Adenosine is normally removed from the bloodstream by an adenosine transporter, which is a protein that takes up adenosine from the blood into cells. The increase in adenosine levels in the blood is variable, and the cause for this variability is unknown. A mutation for this transporter gene may contribute to this variability, and may alter its function. Thus, the purpose of this study is to determine the relationship between the mutation and the transporter function.
Detailed Description

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.

Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
whole blood
Sampling Method Probability Sample
Study Population Subjects undergoing a Persantine nuclear stress test for medically-indicated reasons. There are no control subjects.
Condition
  • Ischemia
  • Coronary Disease
Intervention Not Provided
Study Groups/Cohorts undergoing persantine stress test
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Terminated
Actual Enrollment
 (submitted: January 16, 2013)
221
Original Estimated Enrollment
 (submitted: September 25, 2008)
110
Actual Study Completion Date December 2011
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria

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%)
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT00760708
Other Study ID Numbers 02-115-1
Proposal Number 04156012
Award NumberW81XWH-05-1-0060
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Bruce Liang, UConn Health
Study Sponsor UConn Health
Collaborators United States Department of Defense
Investigators
Principal Investigator: Bruce T Liang, MD UConn Health
PRS Account UConn Health
Verification Date May 2019