The effects of immunostimulation with GM-CSF or IFN-γ on immunoparalysis following human endotoxemia. A parallel randomised double-blind placebo-controlled study

Completed

• Conditions: Blood poisoning; sepsis; 10027665; 10019815

• Registration Number: NL-OMON35765
• Lead Sponsor: niversitair Medisch Centrum Sint Radboud

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 18

Inclusion Criteria

- Age >=18 and <=35
- Male
- Healthy

Exclusion Criteria

- Use of any medication
- History of allergic reaction to GM-CSF/ IFN-γ.
- Smoking.
- Previous spontaneous vagal collapse.
- History, signs or symptoms of cardiovascular disease.
- (Family) history of myocardial infarction or stroke under the age of 65 years.
- Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrioventricular block or a
complex bundle branch block.
- 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 or positive hepatitis serology.
- Positive HIV serology or medical history of any other obvious disease associated with immune deficiency.
- Febrile illness during the week before the LPS challenge.
- Participation in a drug trial or donation of blood 3 months prior to the LPS challenge.
- Chronic hiccups (defined as hiccups longer than 15 minutes in the past 6 months)
- Pre-existent muscle disease (congenital or acquired) or diseases / disorders know to be associated with myopathy including diabetes and auto-immune diseases.
- Pre-existent lung disease
- Upper airway / esophageal pathology
- Recent (< 1 month) nasal bleeding
- Phrenic nerve lesions
- Any metals in body (pacemaker, splinters, metal stitches)

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The main study parameter is the difference in the LPS-induced increase in<br /><br>plasma TNF-a concentration between day 1 and day 7.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary study parameters include plasma levels of other inflammatory<br /><br>mediators, ex vivo production of inflammatory mediators by stimulated<br /><br>leukocytes, monocyte HLA-DR expression, NF*B activation by ROS/RNS,<br /><br>transcriptional activity of leukocytes, changes in phenotype or gene expression<br /><br>caused by mechanisms other than changes in the underlying DNA sequence<br /><br>(epigenetics), urinary markers of tubular injury, twitch transdiaphragmatic<br /><br>pressure, illness score, mean arterial pressure, heart rate and temperature. </p><br>