Immune Modulation by Ischemic Pre-conditioning in Healthy Individuals: Intracellular Signalling in Regulatory Cells

Ischemia Reperfusion Injury Clinical Trial

— KONDI-immun  

Official title:

Immune Modulation by Ischemic Pre-conditioning in Healthy Individuals: Intracellular Signalling in Regulatory Cells

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03541239
• Other study ID #: 1-10-72-298-15
• Status: Completed
• Phase: N/A
• Start date: March 31, 2016
• Est. completion date: July 19, 2016

Study information

• Verified date: June 2016
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to investigate how phosphorylation of STAT3, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) reacts to remote ischemic conditioning (rIC) in healthy humans, which could point to mechanisms by which rIC may protect against ischemia-reperfusion injury (IRI), and if rIC affects immune reactivity.

Description:

In rIC brief episodes of non-lethal ischemia and reperfusion in one vascular bed, tissue or organ, has shown to have protective effects against IRI in various organs. The protective effect of rIC seems convincing, but to date it is not clear which mechanisms give rIC its effects, and why effects are absent in some situations. Effects of rIC on the immune system are also not clear, but important if rIC is used in transplantation and autoimmunity settings, and also in regards to infection risk. Patients studied have often been given medical treatment and/or have comorbidities affecting the results.

This project will measure how intracellular phosphorylation of STAT3, p38 MAPK, ERK and AKT, inflammatory cell patterns and cytokine production react to rIC in healthy humans, and potentially give a better understanding of the mechanisms that mediate the protective effects of rIC. The intracellular mediators studied are involved in the initiation of cytokine production and regulate apoptosis and activation of the inflammatory cells. An altered balance between leucocytes and their mediators could be of importance for rIC effects, particularly in transplantation and autoimmunity, and this will be elucidated in our study.

As a secondary end point the investigators will measure the effect of rIC on pulse variability and blood pressure using a non-invasive device, since evidence regarding these aspects is sparse, although documented positive effects of rIC have primarily been on the heart and vascular system.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: July 19, 2016
• Est. primary completion date: July 19, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Healthy and well

Exclusion Criteria:

• Smoker.

• Taking regular medication.

• Any acute, chronic or systemic disease

• No hard physical exercise 72 hours prior to study participation.

• No alcohol or caffein-containing drinks 24 hours prior to study participation.

• Fasted for at least 6 hours prior to study participation.

Related Conditions & MeSH terms

• Ischaemia Reperfusion Injury
• Ischemia
• Ischemia Reperfusion Injury
• Reperfusion Injury
• Wounds and Injuries

Intervention

Device:
• Single Cuff Tourniquet 8000
If randomized to ischemic conditioning the cuff will be inflated as stated before. If randomized to non-ischemic conditioning the cuff will not be inflated.

Locations

Country	Name	City	State
Denmark	C-Laboratorium, Skejby Sygehus	Aarhus N

Sponsors (3)

Lead Sponsor	Collaborator
University of Aarhus	Erasmus Medical Center, Fonden til Lægevidenskabens Fremme

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in the amount of immune cells in the peripheral blood	The investigators measured the effect of ischemic preconditioning on ischemia reperfusion injury in a randomised controlled cross-over trial with healthy participants. Peripheral blood before and after the intervention was measured.	Baseline before any intervention, 0 minutes and 85 minutes after IRI and 24 hours after IRI
Primary	Changes in inflammatory cytokines in the peripheral blood	The investigators measured the effect of ischemic preconditioning on ischemia reperfusion injury in a randomised controlled cross-over trial with healthy participants. Peripheral blood before and after the intervention was measured.	Baseline before any intervention, 85 minutes after IRI and 24 hours after IRI
Primary	Changes in intracellular activation markers in T-cells	The investigators measured the effect of ischemic preconditioning on ischemia reperfusion injury in a randomised controlled cross-over trial with healthy participants. Peripheral blood before and after the intervention was measured.	Baseline before any intervention, 0 minutes and 85 mins after IRI and 24 hours after IRI
Primary	Changes in intracellular activation markers in monocytes	The investigators measured the effect of ischemic preconditioning on ischemia reperfusion injury in a randomised controlled cross-over trial with healthy participants. Peripheral blood before and after the intervention was measured.	Baseline before any intervention, 0 minutes and 85 minutes after IRI and 24 hours after IRI
Secondary	Measure pulse variability.	Pulse variability was measured during the experiment.	Baseline before any intervention and until 85 minutes after IRI and 24 hours.
Secondary	Measure blood pressure.	Blood pressure was measured during the experiment.	Baseline before any intervention and until 85 minutes after IRI and 24 hours.