In Vivo Effects of C1-esterase Inhibitor on the Innate Immune Response During Human Endotoxemia - VECTOR II (VECTORII)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2013 by Radboud University
Sponsor:
Collaborators:
UMC Utrecht
Sanquin
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT01766414
First received: January 4, 2013
Last updated: January 9, 2013
Last verified: January 2013
  Purpose

Excessive inflammation is associated with tissue damage caused by over-activation of the innate immune system. This can range from mild disease to extreme conditions, such as multiple organ dysfunction syndrome (MODS) and acute respiratory distress (ARDS). In marked contrast to adaptive immunity which is very sensitive to immune modulators such as steroids, the innate immune system cannot be sufficiently targeted by currently available anti-inflammatory drugs.

The investigators hypothesize that pre-treatment with C1-esterase inhibitor in a human endotoxemia model can modulate the innate immune response.

In this study, human endotoxemia will be used as a model for inflammation. Subjects will, prior to endotoxin administration, receive C1 esterase inhibitor or placebo. Blood will be sampled to determine the levels of markers of the innate immune response.


Condition Intervention Phase
Innate Immune Response
Endotoxemia
Inflammation
Sepsis
Drug: C1-esterase inhibitor
Drug: Endotoxin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Official Title: In Vivo Effects of C1-esterase Inhibitor on the Innate Immune Response During Human Endotoxemia - A Randomized Controlled Pilot Study

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • Neutrophil phenotype and redistribution [ Time Frame: 8 hrs after LPS administration ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cytokines and other markers of inflammation [ Time Frame: 8 hrs after LPS administration ] [ Designated as safety issue: No ]
  • C1-inhibitor and complement concentration and activity [ Time Frame: 8 hrs after LPS administration ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: May 2013
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: C1-esterase inhibitor
C1-esterase inhibitor 100 U/kg infusion followed by administration of Endotoxin 2ng/kg
Drug: C1-esterase inhibitor
intravenously
Other Name: Cetor
Drug: Endotoxin
intravenously
Other Name: 2 ng/kg E. coli reference endotoxin 11:H 10:K negative
Placebo Comparator: Placebo
Placebo (saline 0.9%) infusion followed by administration of Endotoxin 2ng/kg
Drug: Endotoxin
intravenously
Other Name: 2 ng/kg E. coli reference endotoxin 11:H 10:K negative

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male volunteers (18-35 years old)

Exclusion Criteria:

  • Relevant medical history
  • Drug-, nicotine-abuses
  • Tendency towards fainting
  • Hyper- or hypotension
  • Use of any medication
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01766414

Contacts
Contact: Peter Pickkers, MD, PhD p.pickkers@ic.umcn.nl

Locations
Netherlands
Radboud University Not yet recruiting
Nijmegen, Netherlands
Principal Investigator: Peter Pickkers, Md, PhD         
Sponsors and Collaborators
Radboud University
UMC Utrecht
Sanquin
  More Information

No publications provided

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT01766414     History of Changes
Other Study ID Numbers: 36688, 2011-002222-46
Study First Received: January 4, 2013
Last Updated: January 9, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Additional relevant MeSH terms:
Inflammation
Endotoxemia
Pathologic Processes
Bacteremia
Sepsis
Infection
Toxemia
Systemic Inflammatory Response Syndrome
Complement C1s
Complement C1 Inactivator Proteins
Complement C1 Inhibitor Protein
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Complement Inactivating Agents
Immunosuppressive Agents

ClinicalTrials.gov processed this record on September 16, 2014