Role of Adenosine in the Release of VEGF and Cytokines

NCT00580905 | Terminated Phase 1

• 2 other identifiers: 070418CRC-1619
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Inflammation

Keywords

Adenosine; Cytokines; Inflammation; VEGF

Outcome Measures

Primary Outcomes (1)

• Plasma levels of cytokines

  6 hours

Study Arms (2)

1

ACTIVE COMPARATOR

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; Drug: Sodium Nitroprusside

2

ACTIVE COMPARATOR

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

Interventions

Adenosine DRUG

IV infusion of adenosine at a dose of 80 mcg/kg/min for 30 minutes.

1

Sodium Nitroprusside DRUG

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)

1

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Inflammation

Interventions

Adenosine; Nitroprusside

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Ferricyanides; Cyanides; Anions; Ions; Electrolytes; Inorganic Chemicals; Ferric Compounds; Iron Compounds; Hydrogen Cyanide; Nitrogen Compounds

Study Officials

• Italo Biaggioni, M.D.

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of medicine and pharmacology

Study Record Dates

• First Submitted: December 17, 2007
• First Posted: December 27, 2007
• Study Start: June 1, 2007
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: February 28, 2018

Record last verified: 2018-02

Locations

US (1)