Adenosine Receptors Influence Ischemia-Reperfusion Injury

Ischemia-Reperfusion Injury Clinical Trial

Official title:

Adenosine Receptor Involvement in Acute Ischemic Preconditioning of the Vascular Endothelium

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT00184847
• Other study ID #: ACAD
• Status: Suspended
• Phase: N/A
• First received: September 12, 2005
• Last updated: March 27, 2008
• Start date: March 2005

Study information

• Verified date: March 2008
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

Ischemic preconditioning is defined as the development of tolerance to ischemia-reperfusion injury by a previous short bout of ischemia resulting in a marked reduction in infarct size. This mechanism can be mimicked by several pharmacological substances such as acetylcholine and adenosine.

To detect ischemia-reperfusion injury in humans in vivo Kharbanda et al. developed a method in which endothelial dysfunction represents the effects of ischemic preconditioning. This method, however, uses acetylcholine to measure endothelial function before and after forearm ischemia. We, the investigators at Radboud University, hypothesize that the use of acetylcholine in this model reduces ischemia-reperfusion injury. Therefore, we will compare this protocol with a protocol in which endothelial function is only measured after ischemia. We expect an increase in ischemia-reperfusion injury when endothelial function is only measured after the forearm ischemia.

After determining the optimal method to measure ischemia-reperfusion injury of the vascular endothelium we will determine the effect of acute and chronic caffeine, an adenosine receptor antagonist, on ischemic preconditioning. With this study we expect to find that adenosine mimics ischemic preconditioning of the vascular endothelium. Moreover, we expect to find that acute caffeine intake reduces ischemia-reperfusion injury whereas chronic caffeine intake does not. This study will increase our knowledge about the mechanism of ischemic preconditioning and may also provide leads to exploit this endogenous protective mechanism in a clinical setting.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 8
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Healthy volunteers

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double-Blind

Related Conditions & MeSH terms

• Ischemia
• Ischemia-Reperfusion Injury
• Reperfusion Injury

Intervention

Drug:
• acetylcholine

Procedure:
• twenty minutes of forearm ischemia

• three 5-minute periods of forearm ischemia

Drug:
• adenosine

• caffeine

Locations

Country	Name	City	State
Netherlands	Radboud University Nijmegen Medical Centre/Department of Pharmacology and Toxicology	Nijmegen	Gelderland

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

Kharbanda RK, Peters M, Walton B, Kattenhorn M, Mullen M, Klein N, Vallance P, Deanfield J, MacAllister R. Ischemic preconditioning prevents endothelial injury and systemic neutrophil activation during ischemia-reperfusion in humans in vivo. Circulation. 2001 Mar 27;103(12):1624-30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentual increase in forearm blood flow ratio to three increment dosages of acetylcholine before forearm ischemia and within two hours after forearm ischemia