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

NCT ID: NCT03541239

Last Updated: 2019-03-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2016-07-19

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.

Conditions

Ischemia Reperfusion Injury; Ischaemia Reperfusion Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Single Cuff Tourniquet 8000

Intervention Type: DEVICE

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.

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.

Group Type: EXPERIMENTAL

Single Cuff Tourniquet 8000

Intervention Type: DEVICE

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.

Interventions

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.

Intervention Type: DEVICE

Other Intervention Names

20-54-711; 20-54-712

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Fonden til Lægevidenskabens Fremme

OTHER

Sponsor Role: collaborator

Erasmus Medical Center

OTHER

Sponsor Role: collaborator

University of Aarhus

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bente Jespersen, Professor

Role: PRINCIPAL_INVESTIGATOR

Dept. of Renal Diseases, SKS, DK

Bjarne Kuno Møller, MD

Role: STUDY_CHAIR

Dept. of Clinical Immunology, SKS, DK

Carla Baan, Professor

Role: STUDY_CHAIR

Erasmus Medical Center

Locations

C-Laboratorium, Skejby Sygehus

Aarhus N, , Denmark

Countries

Denmark

Other Identifiers

1-10-72-298-15

Identifier Type: -

Identifier Source: org_study_id