Role of Adenosine in the Release of VEGF and Cytokines

This study has suspended participant recruitment.
(Study is being reevaluated)
Sponsor:
Information provided by (Responsible Party):
Italo Biaggioni, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00580905
First received: December 17, 2007
Last updated: May 28, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention
Inflammation
Drug: Adenosine
Drug: Sodium Nitroprusside

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Official Title: Role of Adenosine in the Release of VEGF and Cytokines

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Plasma levels of cytokines [ Time Frame: 6 hours ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: June 2007
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
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)
Drug: Adenosine
IV infusion of adenosine at a dose of 80 mcg/kg/min for 30 minutes.
Drug: 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)
Active Comparator: 2

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.

Drug: 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.


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

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00580905

Locations
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Italo Biaggioni, M.D. Vanderbilt University
  More Information

Additional Information:
No publications provided

Responsible Party: Italo Biaggioni, Professor of medicine and pharmacology, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00580905     History of Changes
Other Study ID Numbers: 070418, CRC-1619
Study First Received: December 17, 2007
Last Updated: May 28, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
Adenosine
Cytokines
Inflammation
VEGF

Additional relevant MeSH terms:
Inflammation
Pathologic Processes
Adenosine
Nitroprusside
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anti-Arrhythmia Agents
Cardiovascular Agents
Vasodilator Agents
Antihypertensive Agents
Nitric Oxide Donors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014