NCT01766414

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 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.

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 phase_3

Timeline
Completed

Started Sep 2013

Shorter than P25 for phase_3

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

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 4, 2013

Completed
7 days until next milestone

First Posted

Study publicly available on registry

January 11, 2013

Completed
8 months until next milestone

Study Start

First participant enrolled

September 1, 2013

Completed
1 month until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2013

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2014

Completed
Last Updated

December 2, 2014

Status Verified

November 1, 2014

Enrollment Period

1 month

First QC Date

January 4, 2013

Last Update Submit

November 27, 2014

Conditions

Innate Immune ResponseEndotoxemiaInflammationSepsis

Outcome Measures

Primary Outcomes (1)

  • Neutrophil phenotype and redistribution

    8 hrs after LPS administration

Secondary Outcomes (2)

  • Cytokines and other markers of inflammation

    8 hrs after LPS administration

  • C1-inhibitor and complement concentration and activity

    8 hrs after LPS administration

Study Arms (2)

C1-esterase inhibitor

ACTIVE COMPARATOR

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

Drug: C1-esterase inhibitorDrug: Endotoxin

Placebo

PLACEBO COMPARATOR

Placebo (saline 0.9%) infusion followed by administration of Endotoxin 2ng/kg

Drug: Endotoxin

Interventions

C1-esterase inhibitorDRUG

intravenously

Also known as: Cetor
C1-esterase inhibitor
EndotoxinDRUG

intravenously

Also known as: 2 ng/kg E. coli reference endotoxin 11:H 10:K negative
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-abuses
  • Tendency towards fainting
  • Hyper- or hypotension
  • Use of any medication

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Radboud University

Nijmegen, Netherlands

Location

Related Publications (1)

  • Tak T, Wijten P, Heeres M, Pickkers P, Scholten A, Heck AJR, Vrisekoop N, Leenen LP, Borghans JAM, Tesselaar K, Koenderman L. Human CD62Ldim neutrophils identified as a separate subset by proteome profiling and in vivo pulse-chase labeling. Blood. 2017 Jun 29;129(26):3476-3485. doi: 10.1182/blood-2016-07-727669. Epub 2017 May 17.

    PMID: 28515092DERIVED

MeSH Terms

Conditions

EndotoxemiaInflammationSepsis

Interventions

Complement C1 Inhibitor Proteinlet-363 protein, C elegansEndotoxins

Condition Hierarchy (Ancestors)

BacteremiaInfectionsToxemiaSystemic Inflammatory Response SyndromePathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

GlycoproteinsGlycoconjugatesCarbohydratesComplement C1 Inactivator ProteinsSerpinsPeptidesAmino Acids, Peptides, and ProteinsComplement Inactivator ProteinsComplement System ProteinsImmunoproteinsBlood ProteinsProteinsBacterial ToxinsToxins, BiologicalBiological Factors

Study Officials

  • Hans Hoeven, Prof

    UMC Nijmegen

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 4, 2013

First Posted

January 11, 2013

Study Start

September 1, 2013

Primary Completion

October 1, 2013

Study Completion

January 1, 2014

Last Updated

December 2, 2014

Record last verified: 2014-11

Locations

NL(1)