A study of the effect of the drug C1-esterase inhibitor on the immune system in patients after administration of endotoxin.

Phase 1

• Conditions: Inflammation, SIRS and endotoxemia; MedDRA version: 15.1Level: PTClassification code 10061218Term: InflammationSystem Organ Class: 10018065 - General disorders and administration site conditions; MedDRA version: 15.1Level: LLTClassification code 10060412Term: Septicaemia due to Escherichia coli (E. coli)System Organ Class: 10021881 - Infections and infestations; MedDRA version: 15.1Level: LLTClassification code 10051553Term: Complement factor C1System Organ Class: 100000004848; MedDRA version: 15.1Level: PTClassification code 10040047Term: SepsisSystem Organ Class: 10021881 - Infections and infestations; MedDRA version: 15.1Level: LLTClassification code 10062357Term: SIRSSystem Organ Class: 10018065 - General disorders and administration site conditions; Therapeutic area: Body processes [G] - Immune system processes [G12]

• Registration Number: EUCTR2011-002222-46-NL
• Lead Sponsor: Radboud University Nijmegen Medical Centre

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-03-19
• Last Update Posted: 30 November 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 20

Inclusion Criteria

Age = 18 and = 35 years
Male
Healthy
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Use of any medication
Congenital or acquired C1 inhibitory deficiency
Immune deficiency
Chronic inflammatory diseases
Smoking
History of allergic reaction to blood products
History, signs or symptoms of cardiovascular diseases
(Family) history of cerebrovasculair diseases under the age of 65 years
Previous vagal collaps
Hypertension (defined as RR systolic > 160 or RR diastolic > 90)
Hypotension (defined as RR systolic < 100 or RR diastolic < 50)
Renal impairment (defined as plasma creatinin > 120 µmol/l)
Liver enzyme abnormalities

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The effect of C1-INH prior to induction of a systemic inflammation by endotoxin (E. coli lipopolysaccharide), on the leukocyte <br>phenotype, activation and mobilization. <br>;Primary end point(s): Main study endpoint is the phenotype of circulating neutrophils after LPS in the absence and presence of C1 INH substitution;Timepoint(s) of evaluation of this end point: Before administration of C1-INH/placebo<br>Before administration of LPS<br>1h, 3h, 4.5h, 6h and 8h after LPS injection;Secondary Objective: - Determine the effect of C1-esterase inhibition on the LPS induced pro-inflammatory response (IL-6, TNF-a and IL-1ß) and increase of anti-inflammatory response (IL-10).<br>- Determination of neutrophil lifespans in blood, and post-mitotic pool transit times. These lifespans will be compared between healthy volunteers treated with or without C1-INH before LPS treatment.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Concentration of circulating cytokines after LPS in the absence and presence of C1 INH substitution.<br>- Study the possible differences between the circulatory and post-mitotic pool transit times of neutrophils in human blood in volunteers with and without C1-INH. <br>- Pharmacokinetic and pharmacodynamic data will be collected with respect to the anti-inflammatory effects of C1 INH. <br>- Effects on the PMN phenotype and function will be determined. <br>- C1 INH concentration and activity as well as anaphylatoxin concentrations will be measured and compared to baseline values.;Timepoint(s) of evaluation of this end point: Before administration of C1-INH/placebo<br>Before administration of LPS<br>1h, 3h, 4.5h, 6h and 8h after LPS injection