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

NCT ID: NCT01091571

Last Updated: 2010-11-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2010-10-31

Brief 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.

Conditions

Endotoxemia

Keywords

Adenosine; Endotoxin; Innate Immunity; Dipyridamole

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Endotoxemia placebo

Endotoxin combined with placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo twice daily during seven consecutive days

LPS

Intervention Type: OTHER

The LPS derived from E. coli O:113 2ng/kg iv will be injected in 1 minute at a dosage of 2 ng/kg body weight.

Endotoxemia Dipyridamole

Endotoxin combined with Dipyridamol treatment

Group Type: EXPERIMENTAL

Dipyridamole

Intervention Type: DRUG

Oral treatment with dipyridamole 200 mg twice daily during seven consecutive days

LPS

Intervention Type: OTHER

The LPS derived from E. coli O:113 2ng/kg iv will be injected in 1 minute at a dosage of 2 ng/kg body weight.

Interventions

Dipyridamole

Oral treatment with dipyridamole 200 mg twice daily during seven consecutive days

Intervention Type: DRUG

Placebo

Placebo twice daily during seven consecutive days

Intervention Type: DRUG

LPS

The LPS derived from E. coli O:113 2ng/kg iv will be injected in 1 minute at a dosage of 2 ng/kg body weight.

Intervention Type: OTHER

Other Intervention Names

Persantin retard; Human endotoxemia

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Radboud University Nijmegen Medical Centre

Principal Investigators

Bart P Ramakers, MD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

Radboud University Nijmegen Medical Centre

Nijmegen, , Netherlands

Countries

Netherlands

References

Ramakers BP, Riksen NP, Stal TH, Heemskerk S, van den Broek P, Peters WH, van der Hoeven JG, Smits P, Pickkers P. Dipyridamole augments the antiinflammatory response during human endotoxemia. Crit Care. 2011;15(6):R289. doi: 10.1186/cc10576. Epub 2011 Nov 30.

Reference Type: DERIVED

PMID: 22129171 (View on PubMed)

Other Identifiers

2009/347

Identifier Type: -

Identifier Source: org_study_id