Role of Adenosine in the Release of VEGF and Cytokines

Inflammation Clinical Trial

Official title:

Role of Adenosine in the Release of VEGF and Cytokines

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00580905
• Other study ID #: 070418
• Secondary ID: CRC-1619
• Status: Terminated
• Phase: Phase 1
• First received: December 17, 2007
• Last updated: February 27, 2018
• Start date: June 2007
• Est. completion date: January 2017

Study information

• Verified date: February 2018
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Inflammation

Intervention

Drug:
• Adenosine
IV infusion of adenosine at a dose of 80 mcg/kg/min for 30 minutes.
• Sodium Nitroprusside
To compare the effects of adenosine on increasing cytokines, sodium nitroprusside will be infused at 5 mcg/kg/min (a dose expected to produce similar systemic effects to adenosine)
• Adenosine
The local effects of adenosine or sodium nitroprusside will be studied in response to microinjection (intradermally) of both drugs. Two microdialysis catheters (CMA 100) will be inserted intradermally in the volar aspect of the forearm after numbing the area with local cold (ice applied in the study area). After 30 minutes,one catheter will be infused with sodium nitroprusside (2microliters/min of a 28 mM solution) and the other with adenosine (2mcl/min of a 100 microM solution) will then be started and continued for 60 minutes. Skin blood flow will be monitored throughout the study with the used of a skin laser Doppler fluxometer mounted adjacent to the area of the microdialysis probe. A 2 mm skin biopsy punch will be performed 60 minutes after the end of the infusion.

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma levels of cytokines		6 hours

External Links

•   Vanderbilt Autonomic Dysfunction Center