NCT00785018

Brief Summary

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 failure (MOF). 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. We hypothesize that C1-esterase inhibitor can modulate the innate immune response. In this study, human endotoxemia will be used as a model for inflammation. Subjects will, additionally to endotoxin, receive C1 esterase inhibitor or placebo. Blood will be sampled to determine the levels of markers of the innate immune response.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Nov 2008

Shorter than P25 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

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

Study Start

First participant enrolled

November 1, 2008

Completed
3 days until next milestone

First Submitted

Initial submission to the registry

November 4, 2008

Completed
1 day until next milestone

First Posted

Study publicly available on registry

November 5, 2008

Completed
26 days until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2008

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2009

Completed
Last Updated

April 22, 2011

Status Verified

May 1, 2009

Enrollment Period

1 month

First QC Date

November 4, 2008

Last Update Submit

April 21, 2011

Conditions

EndotoxemiaInflammationMulti Organ Dysfunction Syndrome

Keywords

EndotoxinC1-inhibitorInflammationSepsisMulti organ dysfunction syndromeComplement activation

Outcome Measures

Primary Outcomes (5)

  • Cytokines and other markers of Inflammation

    24 hrs after LPS administration

  • Neutrophil redistribution and phenotype

    24 hours after LPS administration

  • C1-inhibitor and complement concentration and activity

    24 hours after LPS administration

  • Hemodynamic response

    24 hours after LPS administration

  • Markers of Renal Injury

    24 hours after LPS administration

Study Arms (2)

C1-esterase inhibitor

ACTIVE COMPARATOR

Endotoxin 2ng/kg followed by C1- esterase inhibitor 100 U/kg infusion

Drug: C1-esterase inhibitorDrug: Endotoxin administration

Placebo

PLACEBO COMPARATOR

Endotoxin 2ng/kg followed by saline 0.9%(placebo) infusion

Drug: Endotoxin administration

Interventions

C1-esterase inhibitorDRUG

C1-esterase inhibitor 100 U/kg infusion over 30 minutes.

C1-esterase inhibitor
Endotoxin administrationDRUG

2 ng/kg E. coli reference endotoxin 11:H 10:K negative intravenously

C1-esterase inhibitorPlacebo

Eligibility Criteria

Age18 Years - 35 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Healthy male volunteers (18-35 years old)

You may not qualify if:

  • Relevant medical history
  • Drug-, nicotine-, alcohol abuses
  • Tendency towards fainting
  • Hyper- or hypotension

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Radboud University Nijmegen Medical Centre

Nijmegen, 6500HB, Netherlands

Location

MeSH Terms

Conditions

EndotoxemiaInflammationAngioedemas, HereditarySepsis

Interventions

Complement C1 Inhibitor Protein

Condition Hierarchy (Ancestors)

BacteremiaInfectionsToxemiaSystemic Inflammatory Response SyndromePathologic ProcessesPathological Conditions, Signs and SymptomsAngioedemaVascular DiseasesCardiovascular DiseasesHereditary Complement Deficiency DiseasesPrimary Immunodeficiency DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesUrticariaSkin Diseases, VascularSkin DiseasesSkin and Connective Tissue DiseasesHypersensitivity, ImmediateHypersensitivityImmune System DiseasesImmunologic Deficiency Syndromes

Intervention Hierarchy (Ancestors)

GlycoproteinsGlycoconjugatesCarbohydratesComplement C1 Inactivator ProteinsSerpinsPeptidesAmino Acids, Peptides, and ProteinsComplement Inactivator ProteinsComplement System ProteinsImmunoproteinsBlood ProteinsProteins

Study Officials

  • Peter Pickkers, MD, PhD

    Radboud University Nijmegen Medical Centre, The Netherlands

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

November 4, 2008

First Posted

November 5, 2008

Study Start

November 1, 2008

Primary Completion

December 1, 2008

Study Completion

August 1, 2009

Last Updated

April 22, 2011

Record last verified: 2009-05

Locations

NL(1)