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Role of Adenosine in the Release of VEGF and Cytokines

This study has been terminated.
(Not enough volunteer recruited before funding could be secured.)
Sponsor:
ClinicalTrials.gov Identifier:
NCT00580905
First Posted: December 27, 2007
Last Update Posted: February 20, 2017
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.
Information provided by (Responsible Party):
Italo Biaggioni, Vanderbilt University
  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 Phase
Inflammation Drug: Adenosine Drug: Sodium Nitroprusside Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Single (Participant)
Primary Purpose: Other
Official Title: Role of Adenosine in the Release of VEGF and Cytokines

Resource links provided by NLM:


Further study details as provided by Italo Biaggioni, Vanderbilt University:

Primary Outcome Measures:
  • Plasma levels of cytokines [ Time Frame: 6 hours ]

Enrollment: 8
Study Start Date: June 2007
Study Completion Date: January 2017
Primary Completion Date: January 2017 (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

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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:
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
First Submitted: December 17, 2007
First Posted: December 27, 2007
Last Update Posted: February 20, 2017
Last Verified: February 2017

Keywords provided by Italo Biaggioni, 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
Anti-Arrhythmia Agents
Vasodilator Agents
Purinergic P1 Receptor Agonists
Purinergic Agonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Nitric Oxide Donors