Immune Modulation by Ischemic Pre-conditioning in Healthy Individuals: Intracellular Signalling in Regulatory Cells (KONDI-immun)

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.

Study Overview

• Status: Completed
• Conditions: Ischemia Reperfusion Injury; Ischaemia Reperfusion Injury
• Intervention / Treatment: Device: Single Cuff Tourniquet 8000

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 Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus N, Denmark, 8200
    • C-Laboratorium, Skejby Sygehus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: non-ischemic preconditioning; 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.	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.; Other Names: 20-54-711; 20-54-712
Experimental: ischemic preconditioning; 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.	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.; Other Names: 20-54-711; 20-54-712

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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 Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Erasmus Medical Center; Fonden til Lægevidenskabens Fremme
• Investigators: Principal Investigator: Bente Jespersen, Professor, Dept. of Renal Diseases, SKS, DK; Study Chair: Bjarne Kuno Møller, MD, Dept. of Clinical Immunology, SKS, DK; Study Chair: Carla Baan, Professor, Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2016
• Primary Completion (Actual): July 19, 2016
• Study Completion (Actual): July 19, 2016

Study Registration Dates

• First Submitted: June 15, 2016
• First Submitted That Met QC Criteria: May 29, 2018
• First Posted (Actual): May 30, 2018

Study Record Updates

• Last Update Posted (Actual): March 22, 2019
• Last Update Submitted That Met QC Criteria: March 20, 2019
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Ischemia; Wounds and Injuries; Reperfusion Injury
• Other Study ID Numbers: 1-10-72-298-15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No