Clinical trial NCT00580905: Role of Adenosine in the Release of VEGF and Cytokines
Official title: Role of Adenosine in the Release of VEGF and Cytokines
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Inflammation
Keywords: Adenosine
Cytokines
Inflammation
VEGF
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2007-12-27
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The purpose of this study is to extend previous observations in animal models regarding the effects of adenosine in the release of cytokines to human subjects. We intend to accomplish this in two study protocols. In the first we will infuse intravenously adenosine and measure the plasma levels of inflammatory cytokines. In the second one, we will use a microdialysis technique to infuse intradermally small amounts of adenosine and will measure skin blood flow and will take a biopsy to measure levels of mRNA for cytokines.

Detailed description: In Protocol 1 we will infuse adenosine at a dose of 80 mcg/kg/min for 30 minutes while measuring plasma levels of adenosine at different time points, ranging from 30 minutes to 6 hours. Because activation of A2B receptors also mediates the release of inflammatory cytokines, including IL-6, samples will be taken to measure these and other inflammatory/angiogenic cytokines.

In a second protocol, we will administer adenosine intradermically via a microdialysis probe for 30 minutes while we measure the local effect on skin blood flow using laser Doppler techniques. One hour after the end of the infusion we will obtain a skin biopsy from the perfused area for measurement of mRNA for VEGF, IL-8, IL-6 and other cytokines. In addition, we foresee the possibility of further testing looking for and genetic association between angiogenesis and adenosine.

These are proof-of-concept pilot studies. We will study up to 12 subjects in each protocol but an interim analysis will be performed after 6 subjects are studied. This will help us determine if a trend is observed, to perform power calculations, and determine if more extensive studies are warranted.

Eligibility criteria: Inclusion Criteria:

* Age 18-60 yr.
* All potential volunteers will have routine blood test to screen for hepatic, renal, and hematological abnormalities.
* Body mass index \< 27 Kg/m2 .
* Female volunteers of childbearing potential will undergo HCG pregnancy test at screening and again on the study day.

Exclusion Criteria:

* Pregnancy females
* Subjects unable to give voluntary informed consent
* Subjects on anticoagulant drugs or anemic
* Subjects with a recent medical illness
* Subjects with a history of coronary heart disease
* Subjects with known kidney or liver disease
* Subjects with history of asthma
* Recent (past three days) use of phosphodiesterase type 5 (PDE5) inhibitors (sildenafil, tadalafil or vardenafil)
* History of intolerance to adenosine or nitroprusside
* History of methemoglobinemia
* Use of theophylline products
* Subjects with hematological abnormalities

Primary outcomes:
measure: Plasma levels of cytokines
timeFrame: 6 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University
name: Italo Biaggioni, M.D.
role: PRINCIPAL_INVESTIGATOR
References: