Ignite Creation Date:
2024-05-05 @ 6:36 PM
Last Modification Date:
2024-10-26 @ 9:35 AM
Study NCT ID:
NCT00513110
Status:
COMPLETED
Last Update Posted:
2009-10-01
First Post:
2007-08-07
Brief Title:
A Possible Therapeutic Role for Adenosine During Inflammation
Sponsor:
Radboud University Medical Center
Organization:
Radboud University Medical Center
Study Overview
Official Title:
A Possible Therapeutic Role for Adenosine During Inflammation
Status:
COMPLETED
Status Verified Date:
2007-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The adenosine receptor is known for its anti-inflammatory actions and could therefore be a potential target in the treatment of sepsis and septic shock Stimulation of the adenosine receptor could potentially lead to a decrease in inflammation and tissue damage
Under normal conditions adenosine is formed either by an intracellular 5nucleotidase 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 34CT 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
Under normal conditions adenosine is formed either by an intracellular 5nucleotidase 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 34CT 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
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| CMO 2007099 | None | None | None |