Role of Adenosine in the Release of VEGF and Cytokines

Phase 1

Terminated

• Conditions: Inflammation
• Interventions: Drug: Adenosine; Drug: Sodium Nitroprusside

• Registration Number: NCT00580905
• Lead Sponsor: Vanderbilt University

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.

Study Timeline

• Study Start: 2007-06
• Study First Submitted: 2007-12-17
• Study First Submitted QC: 2007-12-20
• Study First Posted: 2007-12-27
• Primary Completion: 2017-01
• Study Completion: 2017-01
• Status Verified: 2018-02
• Last Update Submitted: 2018-02-27
• Last Update Posted: 2018-02-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 8

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	Sodium Nitroprusside	To compare the effects of adenosine at a dose of 80 mcg/kg/min for 30 minutes, Sodium nitroprusside will be used at a dose that produce similar systemic effects (5 mcg/kg/.min)
1	Adenosine	To compare the effects of adenosine at a dose of 80 mcg/kg/min for 30 minutes, Sodium nitroprusside will be used at a dose that produce similar systemic effects (5 mcg/kg/.min)
2	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.

Primary Outcome Measures

Name	Time	Method
Plasma levels of cytokines	6 hours

Trial Locations

Locations (1)

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States