The effect of the a7nACh receptor agonist GTS-21 on inflammation and end-organ dysfunction during human endotoxemia

• Conditions: septic shock; systemic inflammation; 10002252

• Registration Number: NL-OMON32321
• Lead Sponsor: niversitair Medisch Centrum Sint Radboud

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 13 May 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 25

Inclusion Criteria

healthy male volunteers (no medical history, no medication)
age 18-35 years
non-smokers

Exclusion Criteria

Use of any medication
Smoking
History, signs or symptoms of cardiovascular disease
(Family) history of cerebrovascular disease
Previous vagal collaps
Hypertension (defined as RR systolic > 160 or RR diastolic > 90)
Hypotension (defined as RR systolic < 100 or RR diastolic < 50)
Renal impairement (defined as plasma creatinin >120 µmol/l)
Liver enzyme abnormalities or positive hepatitis serology
Positive HIV test

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>the concentration of TNF after the administration of LPS in the absence and<br /><br>presence of GTS-21. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Concentration of pro- and anti-inflammatory cytokines, HMGB-1<br /><br>AChR and TLR expression on circulating monocytes<br /><br>Leucocyte number, C-reactive protein concentration<br /><br>Severity of clinical symptoms, hemodynamic parameters<br /><br>Ex-vivo TLR receptor stimulation assays on whole blood to measure cytokines,<br /><br>AChR and TLR expression.<br /><br>Circulating endothelial cells and markers of endothelial damage (adhesion<br /><br>molecules).<br /><br>Urine excretion of markers of proximal (GSTA1-1) and distal (GSTP1-1) renal<br /><br>tubular damage.<br /><br>Brain specific proteins S100&beta;, NSE, GFAP<br /><br>Vagal activity as measured by heart rate variability analysis</p><br>