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

Not Applicable

Completed

• Conditions: Ischemia Reperfusion Injury; Ischaemia Reperfusion Injury
• Interventions: Device: Single Cuff Tourniquet 8000

• Registration Number: NCT03541239
• Lead Sponsor: University of Aarhus

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2016-03-31
• Status Verified: 2016-06
• Study First Submitted: 2016-06-15
• Primary Completion: 2016-07-19
• Study Completion: 2016-07-19
• Study First Submitted QC: 2018-05-29
• Study First Posted: 2018-05-30
• Last Update Submitted: 2019-03-20
• Last Update Posted: 2019-03-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 19

Inclusion Criteria

• Healthy and well

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
non-ischemic preconditioning	Single Cuff Tourniquet 8000	The participants will have the cuff attached to the arm, however not be inflated for the 4 cycles of remote ischemic conditioning: 1 cycle is 5 minutes of inflation followed by 5 minutes of deflation. The ischemic reperfusion injury was induced by cuff inflation by the Single Cuff Tourniquet 8000 to 200 mmHg in the arm for 20 minutes followed by reperfusion for 15 minutes.
ischemic preconditioning	Single Cuff Tourniquet 8000	The blood supply to the distal part of the arm will be occluded by inflation of a single cuff to 200mmHg, by the help of the Single Cuff Tourniquet 8000, for 5 minutes separated from 5 minutes of deflation, a cycle that happens 4 times in total. The ischemic reperfusion injury was induced by cuff inflation to 200 mmHg in the arm for 20 minutes followed by reperfusion for 15 minutes.

Primary Outcome Measures

Name	Time	Method
Changes in inflammatory cytokines in the peripheral blood	Baseline before any intervention, 85 minutes after IRI and 24 hours after IRI	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.
Changes in intracellular activation markers in T-cells	Baseline before any intervention, 0 minutes and 85 mins after IRI and 24 hours after IRI	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.
Changes in the amount of immune cells in the peripheral blood	Baseline before any intervention, 0 minutes and 85 minutes after IRI and 24 hours after IRI	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.
Changes in intracellular activation markers in monocytes	Baseline before any intervention, 0 minutes and 85 minutes after IRI and 24 hours after IRI	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.

Secondary Outcome Measures

Name	Time	Method
Measure pulse variability.	Baseline before any intervention and until 85 minutes after IRI and 24 hours.	Pulse variability was measured during the experiment.
Measure blood pressure.	Baseline before any intervention and until 85 minutes after IRI and 24 hours.	Blood pressure was measured during the experiment.

Trial Locations

Locations (1)

C-Laboratorium, Skejby Sygehus; 🇩🇰 Aarhus N, Denmark