A Possible Therapeutic Role for Adenosine During Inflammation
NCT ID: NCT00513110
Last Updated: 2009-10-01
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE1
33 participants
INTERVENTIONAL
2007-08-31
2008-08-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Under normal conditions adenosine is formed either by an intracellular 5'nucleotidase, which dephosphorylates AMP, or by the hydrolysis of S-adenosylhomcysteine by hydrolase. An alternative pathway of AMP degradations is provided by the cytosolic enzyme AMP deaminase (AMPD), which catalyses the irreversible deamination of AMP to inosine monophosphate and ammonia.
In humans four AMPD isoforms have been described, named after the source from which they were initially purified; M (muscle), L (liver), E1 and E2 (erythrocyte), encoded by AMPD1, AMPD2 and AMPD3. Approximately 15-20% of Caucasian and African American individuals are heterozygous or homozygous for the 34C\>T variant of AMPD1.
We hypothesize that healthy volunteers who have the polymorphism for AMPD1 have a less severe inflammatory response to LPS and show less (severe) organ failure. This hypothesis is based on the expected higher levels of adenosine in patients with the AMPD1 polymorphism. This hypothesis is strengthened by the fact that patients with coronary artery disease and the AMPD1 polymorphism show improved cardiovascular survival (Anderson JL et al. J Am Coll Cardiol 2000; 36: 1248-52) possibly based on higher adenosine levels by reduced AMPD activity. Furthermore the polymorphism predicts improved clinical outcome in patients with heart failure (Loh E et al. Circulation 1999) also based on a hypothetical elevation of adenosine.
We hypothesize that:
The C34T-polymorphism of the enzyme AMP-deaminase leads to a decreased inflammatory respons and thereby a decrease of LPS-induced tissue damage.
A second hypothesis is based on the antagonism of the adenosine receptor, by caffeine;
Antagonism of the adenosine receptor by caffeine leads to an increased LPS-induced inflammatory reaction and an increase in (subclinical) tissue damage?
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Ibuprofen in Sepsis Study
NCT00000574
The Pharmacokinetics/Pharmacodynamics of High-dose Daptomycin in Patients With Septic Shock
NCT02508350
Adrenomedullin and Outcome in Severe Sepsis and Septic Shock
NCT02393781
Early Tranexamic Acid and Modulating the Inflammatory Response in Sepsis
NCT04910464
Shenfu Injection Improves Arterial Vascular Reactivity
NCT03749525
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
PREVENTION
DOUBLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
1
Endotoxin and AMPD1 polymorphism
AMPD1 polymorphism
Endotoxin 2ng/kg to subjects with a AMPD1 polymorphism
2
Endotoxin and intervention with caffeine
Caffeine infusion
Endotoxin 2ng/kg combined with caffeine. Caffeine (4mg/kg) is used as an adenosine receptor antagonist.
3
Endotoxin combined with placebo
placebo
Endotoxin 2ng/kg combined with saline infusion (0.9%)
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
AMPD1 polymorphism
Endotoxin 2ng/kg to subjects with a AMPD1 polymorphism
Caffeine infusion
Endotoxin 2ng/kg combined with caffeine. Caffeine (4mg/kg) is used as an adenosine receptor antagonist.
placebo
Endotoxin 2ng/kg combined with saline infusion (0.9%)
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
Exclusion Criteria
* Tendency towards fainting
* Relevant medical history
18 Years
35 Years
MALE
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Radboud University Medical Center
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Radboud University Nijmegen Medical Centre
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Peter Pickkers, MD,PhD
Role: PRINCIPAL_INVESTIGATOR
Radboud University Medical Center
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, Netherlands
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Ramakers BP, Riksen NP, van den Broek P, Franke B, Peters WH, van der Hoeven JG, Smits P, Pickkers P. Circulating adenosine increases during human experimental endotoxemia but blockade of its receptor does not influence the immune response and subsequent organ injury. Crit Care. 2011;15(1):R3. doi: 10.1186/cc9400. Epub 2011 Jan 6.
van den Boogaard M, Ramakers BP, van Alfen N, van der Werf SP, Fick WF, Hoedemaekers CW, Verbeek MM, Schoonhoven L, van der Hoeven JG, Pickkers P. Endotoxemia-induced inflammation and the effect on the human brain. Crit Care. 2010;14(3):R81. doi: 10.1186/cc9001. Epub 2010 May 5.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
CMO 2007/099
Identifier Type: -
Identifier Source: secondary_id
2007/099
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.