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The Effects of Oral Dipyridamole Treatment on the Innate Immune Response During Human Endotoxemia

Information source: Radboud University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Endotoxemia

Intervention: Dipyridamole (Drug); Placebo (Drug); LPS (Other)

Phase: Phase 4

Status: Completed

Sponsored by: Radboud University

Official(s) and/or principal investigator(s):
Bart P Ramakers, MD, Principal Investigator, Affiliation: Radboud University

Summary

During sepsis and septic shock the immune response can be overwhelming leading to excessive tissue damage, organ failure and death. Ideally, the inflammatory response is modulated leading to both adequate protection to invading pathogens as well as limitation of an exuberant immune response. In the last few years adenosine is proposed to have a central role in the modulation of inflammation. In unfavorable conditions such as hypoxia, ischemia or inflammation adenosine is quickly up-regulated; with concentrations up to tenfold in septic patients. Many animal studies have shown that adenosine is able to attenuate the inflammatory response and decrease mortality rates. Therefore, pharmacological elevation of the adenosine concentration is an potential target to attenuate inflammation and limit organ injury. Dipyridamole, an adenosine re-uptake inhibitor is able to increase the adenosine concentration and limit ischemia-reperfusion injury. In order to study the effects of dipyridamole on the inflammatory response we aim to use the so called human endotoxemia model. This model permits elucidation of key players in the immune response to a gram negative stimulus in vivo, therefore serving as a useful tool to investigate potential novel therapeutic strategies in a standardized setting.

Clinical Details

Official title: The Effects of Oral Dipyridamole Treatment on the Innate Immune Response During Human Endotoxemia.

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Primary outcome: Circulating cytokines

Secondary outcome:

Hemodynamics

Sensitivity to norepinephrine

Endothelial-dependent and independent vasorelaxation

Markers of endothelial damage and circulating endothelial cells

Urinary excretion of markers of renal injury

Adenosine and related nucleotide concentrations

Additional blood samples will be drawn for genetic testing and measurement of: mRNA and proteins part of the adenosine metabolism

Oxydative stress

Eligibility

Minimum age: 18 Years. Maximum age: 35 Years. Gender(s): Male.

Criteria:

Inclusion Criteria:

- Age ≥ 18 and ≤ 35 years

- Male

- Healthy

Exclusion Criteria:

- Use of any medication.

- History of allergic reaction to dipyridamole

- Bleeding disorder.

- Smoking.

- Previous spontaneous vagal collapse.

- History, signs or symptoms of cardiovascular disease.

- Cardiac conduction abnormalities on the ECG consisting of a 2nd degree

atrioventricular block or a complex bundle branch block.

- Hypertension (defined as RR systolic > 160 or RR diastolic > 90).

- Hypotension (defined as RR systolic < 100 or RR diastolic < 50).

- Renal impairment (defined as plasma creatinin >120 μmol/l).

- Liver enzyme abnormalities or positive hepatitis serology.

- Positive HIV serology or any other obvious disease associated with immune deficiency.

- Febrile illness in the week before the LPS challenge.

- Participation in another drug trial or donation of blood 3 months prior to the

planned LPS challenge.

Locations and Contacts

Radboud University Nijmegen Medical Centre, Nijmegen 6500 HB, Netherlands
Additional Information

Starting date: March 2010
Last updated: November 4, 2010

Page last updated: August 23, 2015

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