Role of Adenosine in the Release of VEGF and Cytokines

February 27, 2018 updated by: Italo Biaggioni, Vanderbilt University
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
8

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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)
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.
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
IV infusion of adenosine at a dose of 80 mcg/kg/min for 30 minutes.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Plasma levels of cytokines
Time Frame: 6 hours
6 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Vanderbilt University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 17, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 20, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 27, 2007

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 28, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 27, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 070418
  • CRC-1619

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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