Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

the Influence of Remote Ischemic Preconditioning on Inflammation During Human Endotoxemia (RISPENDO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02602977
Recruitment Status : Completed
First Posted : November 11, 2015
Last Update Posted : April 4, 2016
Sponsor:
Information provided by (Responsible Party):
Radboud University

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.

Condition or disease Intervention/treatment Phase
Autoimmune Diseases Infection Other: Multiple-dose Remote Ischemic Preconditioning Other: Single-dose Remote Ischemic Preconditioning Biological: LPS infusion Early Phase 1

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: the Influence of Remote Ischemic Preconditioning on Inflammation During Human Endotoxemia, a Pilot Proof-of-principle Study
Study Start Date : October 2015
Actual Primary Completion Date : March 2016
Actual Study Completion Date : March 2016

Arm Intervention/treatment
Experimental: multiple-dose RIPC
Multiple-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.
Other: Multiple-dose Remote Ischemic Preconditioning

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.

Other Name: RIPC

Biological: LPS infusion
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.
Other Name: human endotoxemia

Experimental: single-dose RIPC
Single-dose Remote Ischemic Preconditioning. A group of 10 subjects that will receive a single RIPC dose, starting 40 minutes before LPS administration.
Other: Single-dose Remote Ischemic Preconditioning

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

Other Name: RIPC

Biological: LPS infusion
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.
Other Name: human endotoxemia

Active Comparator: control group
Only LPS infusion. A group of 10 subjects that will be administered LPS without RIPC.
Biological: LPS infusion
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.
Other Name: human endotoxemia




Primary Outcome Measures :
  1. Plasma TNF-α concentration following LPS administration [ Time Frame: 1 day ]
    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.


Secondary Outcome Measures :
  1. circulating cytokines (including but not limited to IL-6, IL-10, IL-1RA) [ Time Frame: 1 day ]
  2. Hemodynamic parameters [ Time Frame: 1 day ]
    blood pressure, heart frequency, respiratory frequency

  3. body temperature [ Time Frame: 1 day ]
  4. subjective symptom scores [ Time Frame: 1 day ]
    The subject is asked to score the severity of experienced symptoms every 30 minutes throughout the experiment. Symptom are scored on a scale ranging from 0, (symptom not present) to 5 (worst ever experienced).

  5. kidney injury markers in urine - TIMP2*IGFBP7 [ Time Frame: 1 day ]
    TIMP2*IGFBP7 (expressed in ng/ml^2) is a combined marker that is measured using the NephroCheck Test (Astute Medical, San Diego, CA, USA).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • History of asthma
  • Obvious disease associated with immune deficiency
  • CRP > 20 mg/L, WBC > 12x109/L, or clinically significant acute illness, including infections, within 4 weeks before endotoxemia day

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02602977


Locations
Layout table for location information
Netherlands
Radboud University Medical Centre, Intensive Care
Nijmegen, Netherlands, 6525 GA
Sponsors and Collaborators
Radboud University
Investigators
Layout table for investigator information
Principal Investigator: Jelle Zwaag, MSc Radboud University
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT02602977    
Other Study ID Numbers: RISPENDO
First Posted: November 11, 2015    Key Record Dates
Last Update Posted: April 4, 2016
Last Verified: April 2016
Keywords provided by Radboud University:
inflammation
remote ischemic preconditioning
Additional relevant MeSH terms:
Layout table for MeSH terms
Endotoxemia
Autoimmune Diseases
Inflammation
Pathologic Processes
Immune System Diseases
Bacteremia
Sepsis
Infection
Toxemia
Systemic Inflammatory Response Syndrome