Plain English Summary
Background and study aims
Cardiovascular events such as heart attacks and strokes are the main cause of illness and death in western countries. Remote ischemic preconditioning (RIPC) is a feasible and practical method to protect the heart against damage after surgery. It is produced by repeated short periods of oxygen interruption using a blood pressure cuff at the upper arm. Serum is the part of blood that is like water and that contains substances (called antibodies) that fight disease. The aim of this study is to find out whether serum taken from male volunteers that underwent this procedure can protect certain cells from a artificially induced absence of oxygen.
Who can participate?
Healthy male volunteers, age 18-45 years.
What does the study involve?
For the remote ischaemic conditioning stimulus, a pressure cuff will be placed on the upper arm and inflated for 5 minutes. Pressure will be released during 5 minutes, after which the cycle will be repeated three more times for a total of four cycles. Blood samples will be taken at three different time points and the blood will be used in the laboratory for further investigations.
What are the possible benefits and risks of participating?
There are no direct benefits or risks for the volunteer. Remote ischaemic conditioning is in itself a safe intervention. Volunteers can experience slight discomfort during inflation of the tourniquet around their upper arm. Blood withdrawal can also give a slight discomfort but is without risk for the volunteer.
Where is the study run from?
Academic Medical Centre (AMC) (Netherlands).
When is the study starting and how long is it expected to run for?
The study ran from June to August 2012.
Who is funding the study?
Academic Medical Centre (AMC) (Netherlands).
Who is the main contact?
Prof Benedikt Preckel
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
NL38188.018.11
Study information
Scientific title
Mechanisms of Remote Ischemic PreConditioning in humans: prevention of cellular damage by serum collected after remote conditioning of the upper arm of human male volunteers
Acronym
Me-RIPC
Study hypothesis
We hypothesize that serum taken from volunteers subjected to remote ischemic conditioning of the upper arm can protect different human umbilical vein endothelial cells from hypoxia-reperfusion induced damage. If we find protection we aim to investigate the underlying mechanism of this protection in the in vitro model.
Ethics approval
Medical Ethics Committee of the Academic Medical Center in Amsterdam, 12/01/2012, METC Number: 2012_014, ABR Number: NL38188.018.11
Study design
Researcher blinded study
Primary study design
Interventional
Secondary study design
Non randomised controlled trial
Trial setting
Other
Trial type
Screening
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Myocardial infarction, endothelial disease
Intervention
On the day of participation, a physical examination (cardiopulmonary system) will be performed by a physician prior to the start of the investigational intervention.
The investigational intervention is a remote ischaemic conditioning stimulus. Hereto, a pressure cuff will be placed on the upper arm and inflated to 200 mmHg for 5 minutes. Then, pressure will be released during 5 minutes allowing reperfusion, after which the cycle will be repeated three more times for a total of four cycles. The stimulus will be applied five minutes after T0 blood sampling. Five- and sixty minutes after completion of Remote Ischaemic Conditioning stimulus, T1 and T2 blood will be sampled. Each blood withdrawal will be taken by a separate venous puncture performed by a physician with extensive experience in this field.
For each experiment 100 µl serum per 6-well is needed. The experiment will be repeated three times for each cell type. 45% of the blood withdrawn is hematocrit, thus per time point 22cc blood will be sampled, after centrifugation (to separate cells from the serum) approximately 12cc serum will be left to do the in vitro experiments. In total, the volunteer gives 66cc blood. Samples will not be stored for purposes other than completion of the in vitro experiments.
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measures
Lactate dehydrogenase enzyme (LDH) release in human umbilical vein endothelial cells measured at different time points in our in vitro model after incubation with the serum.
Secondary outcome measures
1. We measured mitogen activated protein kinase ERK 1/2, protein kinase B (AKT) and hypoxia inducible factor (HIF) 1 alpha in the endothelial cells by the use of western blotting at time point T0 before remote preconditioning and T1 (after 45 minutes, directly after the remote conditioning protocol).
2. We measured human vascular endothelial growth factor in the plasma of the volunteers also at T0 and T1.
Overall trial start date
15/06/2012
Overall trial end date
28/08/2012
Reason abandoned
Eligibility
Participant inclusion criteria
Healthy male volunteers aged 18-45 years.
Participant type
Patient
Age group
Adult
Gender
Male
Target number of participants
10
Participant exclusion criteria
1. Any cardiovascular, kidney, pulmonary or endocrine diseases
2. Alcohol or drug abuse
3. No informed consent
Recruitment start date
15/06/2012
Recruitment end date
28/08/2012
Locations
Countries of recruitment
Netherlands
Trial participating centre
Department of Anesthesiology
Amsterdam
1105 AZ
Netherlands
Funders
Funder type
University/education
Funder name
Academic Medical Centre (AMC) (Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary