Ischemic Preconditioning - Perspectives of Use Vivio/in Vitro Studies

NCT07117643 | Enrolling By Invitation

• 2 other identifiers: AWFiS/2025_7_JM2/16/12/2024
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 2

Brief Summary

Both in sports and medicine, methods that can significantly contribute to improving the ability of tissues to perform their functions are constantly being searched. One of those methods that is increasingly used also in sports is remote ischemic preconditioning (RIPC). Mostly, this procedure involves repeated brief cycles of limb ischemia/reperfusion. This method is often referred as ischemic blood reperfusion and helps to increase the tolerance of treated tissues to the occurrence of possible ischemic episodes in the future. Numerous studies have shown that RIPC induces changes that lead to increased resistance to hypoxia and other stressors in organs (brain, heart, liver). In addition, it has been proven that induction of arterial occlusion in the area of selected limbs before performing physical exercises can affect the improvement of their function, and thus can translate into sports results. In addition, an adaptation of such fibres to damage is mostly associated with the secretion of many factors that influence body function. That's why we conclude that it may affect protein kinases (such like c-Jun N-terminal kinases (JNKs) or serine-threonine kinase = protein kinase B (AKTs)) whose main role is regulation of the activity of a wide spectrum of substrates, influencing cells proliferation, apoptosis, responses to cellular stress and inflammatory process in normal and cancer cells. Concluding that presented kinases activity is associated with cells differentiation and RIPC and physical activity may affect them and the inflammation process that may lead to cytotoxic activity against cancer cells (especially if the effects are combined together). The beneficial increase of anti-tumour activity of the blood serum against pathological isolated tumour cells of prostate cancer (cell lines - LNCaP and PC- 3) was confirmed in our pilot studies. We observed an increase in the anti-cancer properties of serum taken from people that attended RIPC training and performed physical activity. However, the exact mechanism and associated changes in the proteome of blood serum people attending in the RIPC training have not yet been determined. This knowledge would allow us to determine the exact mechanisms of the reperfusion/reocclusion training on the human body and its beneficial activity. Considering that the skeletal muscle is an organ capable of synthesis and release of a number of proteins, cytokines and low molecular weight compounds, especially during physical activity, it should be assumed that intermittent muscle ischemic episodes will lead to increased release of factors that will increase the resistance of muscles and other tissues to stress. At the same time, it was noticed that under conditions of muscular stress induced changes in iron metabolism occur. The binding of free iron through the ferritin protein at the cell level leads to its greater resistance to stressors. In the prism of the above considerations, the results of our preliminary studies showing that the upper limb RIPC procedures cause changes in iron metabolism in white blood cells and may suggest that the procedure of RIPC leads to changes that allow storing iron in a safe form in as ferritin. At the same time, with the increasing interest in iron metabolism, the role and function of amyloid precursor protein (APP) and hepcidin are increasing. It has been proven that APP is a protein that works with ferroportin, thus taking part in iron export from a cell. Moreover, it has been shown that the post-translational modification of APP leads to the formation of amyloid α (determines positive changes) and amyloid β (negative changes). Because there are some indications that sAPPα may be modified by iron changes and associated with cfDNA changes, which substantially increase during i.e. tissue damage, we would like to explore those correlations more deeply. The same decrease in the APP protein level will lead to the inhibition of iron export from the cell and an increase of its concentration in the cell. The nature of such changes in iron metabolism should be considered as adaptive to the ischemic stress on which muscle is exposed during the RIPC procedure. The increase in ferritin in the cell leads to a decrease in the concentration of free iron and thus a reduction in iron-dependent ROS formation. This project will have an impact on the development of the current state of knowledge of the mechanisms of biochemical response to the specific tissue-affecting method in form of remote ischemic preconditioning and will allow determining the role of sAPPα and Cathepsin C and other trophic factors and changes in iron metabolism in this process, taking into account the role of hepcidin and vitamin D. Moreover, the present project may contribute to the determination of the role of presented procedures on cells proliferation, as an example of anti-tumour proprieties, and changes of human serum proteomes.

Conditions

Sport Medicine; Sport; Physiological Adaptations; Sport Performance; Remote Ischemic Preconditioning; Ischemic Preconditioning

Keywords

inflammation; remote ischemic preconditioning; hepcidin; Iron; erytropheron; RIPC; IPC

Outcome Measures

Primary Outcomes (4)

• Measurement of the inflammation blood markers using Magnetic Luminex Performance Assays

  The intake will be performed in appropriate standardized BD Vacutainer tubes by qualified medical personnel: Serum and plasma will be separated from the samples, Each sample to obtain the serum will be centrifuged at 2500-3000 rpm for 10 minutes in 4° C and stored in 1.5 ml tubes at - 80° C until the assay (no longer than 6 months). The following secretory factors and markers of inflammation will be determined in serum or blood plasma (depending on the requirements of the method used) and then analysed in detail using immu: * high sensitive C-protein (hsCRP), * creatine kinas (CK), * lactic acid (LA), * interleukin 6 (IL6), * interleukin 10 (IL10), * interleukin 15 (IL15),

  Change from baseline at 24 hours after fatigue-induced exercise (before and after IPC protocol)

• Measurement of the Iron metabolism blood markers using Magnetic Luminex Performance Assays and ELISA Assays

  The intake will be performed in appropriate standardized BD Vacutainer tubes by qualified medical personnel: Serum and plasma will be separated from the samples, Each sample to obtain the serum will be centrifuged at 2500-3000 rpm for 10 minutes in 4° C and stored in 1.5 ml tubes at - 80° C until the assay (no longer than 6 months). The following secretory factors and markers will be messured: * free Iron * hepcidin, * transferrin, * ferritin, * EPO, * EFRE, * TIBC,

  Change from baseline at 24 hours after fatigue-induced exercise (before and after IPC protocol)

• Measurement of neurotrophic, angiogenic blood markers using Automated Hematology Analyzers and Magnetic Luminex Performance Assays

  The intake will be performed in appropriate standardized BD Vacutainer tubes by qualified medical personnel: Serum and plasma will be separated from the samples, Each sample to obtain the serum will be centrifuged at 2500-3000 rpm for 10 minutes in 4° C and stored in 1.5 ml tubes at - 80° C until the assay (no longer than 6 months). The following secretory factors and markers of inflammation will be determined: angiogenin (ANG), • insulin-like growth factor-1 (IGF-1), • Growth Differentiation Factor 15 (GDF15), • nerve growth factor (NGF), • Amyloid Precursor Protein- α (sAPPα), • angiopoietin (ANGP1), • brain-derived neurotrophic factor (BDNF) • growth differentiation factor 15 (GDF-15), • tumor necrosis factor α (TNFα).

  Change from baseline at 24 hours after fatigue-induced exercise (before and after IPC protocol)

• The general assessment of the homoeostasis Automated Hematology Analyzers

  * blood morphology, * glycemia, * free iron, * activity of alanine aminotransferase (ALT), * aspartate aminotransferase (AST), * creatine kinase (CK), * lactate dehydrogenase (LDH), * concentration of insulin, * total cholesterole * creatinine,

  Before all procedures and before post-IPC testing

Secondary Outcomes (5)

• Measurement of proteins involved in antioxidant defence using Western Blotting Techniques

  Change from baseline at 24 hours after fatigue-induced exercise (before and after IPC protocol)

• Measurement of anaerobic power of the lower limbs (Wingate Anaerobic Test)

  Before and after 1-time and 10-times IPC/SHAM procedures

• Messurment of cfDNA changes

  Before, and 5 min, 60 min after every WAnT performance

• Measurement of isolated serum cytotoxic activity

  Up to 3 months post-experimental period

• Body composition analyses using bioelectrical impedance analysis (BIA)

  During the initial visit, and before and after every experimental phase (1-time; 10-times IPC procedures)

Study Arms (4)

1-time SHAM intervention

SHAM COMPARATOR

1 time SHAM intervention

Other: Ischemic Preconditioning

10-time SHAM intervention

SHAM COMPARATOR

10-time SHAM intervention

Other: Ischemic Preconditioning

1-time RIPC intervention

EXPERIMENTAL

1-time RIPC intervention on anaerobic/aerobic performance

Other: Ischemic Preconditioning

10-time RIPC intervention

EXPERIMENTAL

10-time RIPC intervention on anaerobic/aerobic performance

Other: Ischemic Preconditioning

Interventions

Ischemic Preconditioning OTHER

The ischemic procedure will be carried out before the start of the WanT and eccentric exercises procedures and muscle damage in accordance with the detailed description of the RIPC procedure. Four-fold filling of the flotation flange will be performed by 5 minutes to the value of 200 mm Hg with 5 minutes' rest interval near the attachment of the initial straight thigh muscle. All performed procedures will be carried out under the Doppler USG control to perform full arterial blood flow restriction. The whole research will be carried out in the Laboratory in morning hours. Each participant will be in a hydrated state and before the first meal.

Also known as: IPC, RIPC, REPERFUSION/REOCCLUSION TRAINING

1-time RIPC intervention; 1-time SHAM intervention; 10-time RIPC intervention; 10-time SHAM intervention

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Dependent on the studied population:
• Population of not training grope age and morphologically appropriate participation will take part. Participants will be recruited basing on a voluntary letter of intent. All representatives of the analyzed group participating in the pre-qualification research will fill in the physical activity sheet - Global Health Activity Questionnaire - World Health Organization in Polish adaptation. This will allow to eliminate people who report high levels of physical activity (similar to the level of sport training individuals).
• Aerobic sport training Population (long distance runners, marathon runners and other). Participants will be recruited basing on a voluntary letter of intent. All representatives of the analysed group participating in the pre-qualification research will fill in the physical activity sheet - Global Health Activity Questionnaire - World Health Organization in Polish adaptation. All participants have to declare minimum 5 marathon run history (similar to the level of sport results during the run).

You may not qualify if:

• taking medicines during the study,
• history of cardiovascular disorders,
• history of autonomic nervous system disorders,
• history of mental disorders,
• history of cerebro-cranial traumas,
• history of other diseases that may directly affect obtained results,
• concurrent injuries,
• drugs intake,
• supplements consumption

Sponsors & Collaborators

• Gdansk University of Physical Education and Sport: lead
• Medical University of Gdansk: collaborator
• Kazimierz Wielki University: collaborator
• Università Politecnica delle Marche: collaborator
• Charles University, Czech Republic: collaborator

Study Sites (2)

Gdansk University of Physical Education and Sport

Gdansk, Pomeranian Voivodeship, 80-336, Poland

Location

University of Physical Education and Sport (GUPES)

Gdansk, Pomeranian Voivodeship, 80-336, Poland

Location

Related Publications (15)

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• Vasques JF, Heringer PVB, Goncalves RGJ, Campello-Costa P, Serfaty CA, Faria-Melibeu ADC. Monocular denervation of visual nuclei modulates APP processing and sAPPalpha production: A possible role on neural plasticity. Int J Dev Neurosci. 2017 Aug;60:16-25. doi: 10.1016/j.ijdevneu.2017.03.003. Epub 2017 Mar 18.

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Related Links

• Metadata

MeSH Terms

Conditions

Inflammation

Interventions

Ischemic Preconditioning; Reperfusion

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics; Investigative Techniques; Cardiovascular Surgical Procedures; Surgical Procedures, Operative; Perfusion

Study Officials

• Jędrzej Antosiewicz, Full Profesor

  Medical University of Gdańsk, Department of Bioenergetics and Physiology of Exercise, Gdańsk, Poland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2025
• First Posted: August 12, 2025
• Study Start: January 1, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: August 12, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

PL (2)