the Influence of Remote Ischemic Preconditioning on Inflammation During Human Endotoxemia
RISPENDO
1 other identifier
interventional
30
1 country
1
Brief Summary
In a wide range of auto-inflammatory and infectious diseases attenuation of the immune response could be beneficial. Remote ischemic preconditioning (RIPC) has been identified as a means of protecting patients undergoing cardiac surgery from perioperative myocardial ischemic damage. This protection can be divided in a 'first window of protection' directly after preconditioning and a 'second window' that protects patients 12-48 hour after preconditioning. Repeated RIPC might have additional value, possibly by combining beneficial effects of the first and second windows of protection. The mechanisms behind these effects are under investigation, but attenuation of the inflammatory response is a major candidate. However, this has not yet been demonstrated in the setting of systemic inflammation in humans in vivo. This study aims to investigate the effects of (repeated) ischemic preconditioning on inflammation during human endotoxemia.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for early_phase_1
Started Oct 2015
Shorter than P25 for early_phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 30, 2015
CompletedStudy Start
First participant enrolled
October 1, 2015
CompletedFirst Posted
Study publicly available on registry
November 11, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2016
CompletedApril 4, 2016
April 1, 2016
5 months
September 30, 2015
April 1, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Plasma TNF-α concentration following LPS administration
The primary study parameter is the difference in circulating TNF-α concentration over time between the multiple-dose (7 days) RIPC group and the control group.
1 day
Secondary Outcomes (5)
circulating cytokines (including but not limited to IL-6, IL-10, IL-1RA)
1 day
Hemodynamic parameters
1 day
body temperature
1 day
subjective symptom scores
1 day
kidney injury markers in urine - TIMP2*IGFBP7
1 day
Study Arms (3)
multiple-dose RIPC
EXPERIMENTALMultiple-dose Remote Ischemic Preconditioning. A group of 10 subjects that will receive 4 cycles of remote ischemic preconditioning of the upper limb per day in the 7 consecutive days before the endotoxemia experiment. The last dose will be applied 40 minutes before LPS administration.
single-dose RIPC
EXPERIMENTALSingle-dose Remote Ischemic Preconditioning. A group of 10 subjects that will receive a single RIPC dose, starting 40 minutes before LPS administration.
control group
ACTIVE COMPARATOROnly LPS infusion. A group of 10 subjects that will be administered LPS without RIPC.
Interventions
A blood-pressure cuff with handheld rubber inflation balloon and manometer is placed on the non-dominant arm of the subject. The cuff will be placed proximally from the elbow with the most proximal part of the cuff placed in the armpit. The cuff will be inflated to 250 mmHg after which a 5 minute countdown is started. After 5 minutes the pressure is released and the 5 minute countdown for reperfusion is started. This concludes one cycle out of a total of four. 1 "RIPC-dose" consists of 4 cycles of 5 minute ischemia followed by 5 minute reperfusion as described above. Multiple-dose RIPC consists of a daily dose of 1 RIPC as described above for 7 consecutive days.
A blood-pressure cuff with handheld rubber inflation balloon and manometer is placed on the non-dominant arm of the subject. The cuff will be placed proximally from the elbow with the most proximal part of the cuff placed in the armpit. The cuff will be inflated to 250 mmHg after which a 5 minute countdown is started. After 5 minutes the pressure is released and the 5 minute countdown for reperfusion is started. This concludes one cycle out of a total of four. 1 "RIPC-dose" consists of 4 cycles of 5 minute ischemia followed by 5 minute reperfusion as described above. Single-dose RIPC consists of 1 dose of RIPC as described above
To achieve a controlled inflammatory state, 30 subjects (multiple-dose RIPC group \[n=10\], single-dose RIPC group \[n=10\] and control group \[n=10\]) will receive LPS intravenously. The LPS at a dose of 2 ng/kg iv will be injected in 1 minute.
Eligibility Criteria
You may qualify if:
- Written informed consent to participate in this trial
- Male subjects aged 18 to 35 years inclusive
- Healthy as determined by medical history, physical examination, vital signs, 12-lead electrocardiogram and clinical laboratory parameters
You may not qualify if:
- Use of any medication
- Smoking
- Use of recreational drugs within 21 days prior to endotoxemia experiment day
- Use of caffeine or alcohol within 1 day prior to endotoxemia experiment day
- Previous participation in a trial where LPS was administered
- Surgery or trauma with significant blood loss or blood donation within 3 months prior to endotoxemia experiment day
- Participation in another clinical trial within 3 months prior to endotoxemia experiment day
- History, signs, or symptoms of cardiovascular disease
- History of frequent vaso-vagal collapse or of orthostatic hypotension
- History of atrial or ventricular arrhythmia
- Hypertension (RR systolic \>160 or RR diastolic \>90)
- Hypotension (RR systolic \<100 or RR diastolic \<50)
- Conduction abnormalities on the ECG consisting of a 1st degree atrioventricular block or a complex bundle branch block
- Renal impairment: plasma creatinine \>120 µmol/L
- Liver function abnormality: alkaline phosphatase\>230 U/L and/or ALT\>90 U/L
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Radboud University Medical Centre, Intensive Care
Nijmegen, 6525 GA, Netherlands
Related Publications (1)
Zwaag J, Beunders R, Warle MC, Kellum JA, Riksen NP, Pickkers P, Kox M. Remote ischaemic preconditioning does not modulate the systemic inflammatory response or renal tubular stress biomarkers after endotoxaemia in healthy human volunteers: a single-centre, mechanistic, randomised controlled trial. Br J Anaesth. 2019 Aug;123(2):177-185. doi: 10.1016/j.bja.2019.03.037. Epub 2019 May 10.
PMID: 31084985DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jelle Zwaag, MSc
Radboud University Medical Center
Study Design
- Study Type
- interventional
- Phase
- early phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 30, 2015
First Posted
November 11, 2015
Study Start
October 1, 2015
Primary Completion
March 1, 2016
Study Completion
March 1, 2016
Last Updated
April 4, 2016
Record last verified: 2016-04