Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02922673
Other study ID # SALYCENDO
Secondary ID 2016-001971-61NL
Status Completed
Phase N/A
First received
Last updated
Start date September 2016
Est. completion date September 2017

Study information

Verified date September 2016
Source Radboud University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Rationale:

The last years, research focus has moved to immunostimulatory agents in order to restore or increase the functionality of the immune system during sepsis-induced immunoparalysis. Epidemiologic data show that prehospital use of low dose acetylsalicylic acid (ASA) is associated with improved outcome of sepsis. Experimental data indicate that ASA exerts pro-inflammatory effects during systemic inflammation. However, it remains to be determined whether treatment with ASA improves immune function once immunoparalysis has developed and whether prehospital use of low dose ASA prevents the development of immunoparalysis. In the former case, ASA is a potential immunostimulatory therapy that can treat sepsis-induced immunoparalysis. In the latter case, ASA may have a broader indication as an immunomodulating agent. Taken together, ASA might be a promising, cheap, well-known, and globally available agent to reduce the incidence of secondary infections and improve patient outcome in sepsis.

Objective:

- To determine whether acetylsalicylic acid treatment can reverse endotoxin tolerance, which is expressed as a decrease in pro-inflammatory cytokine levels between the first and second endotoxin challenge.

- To determine whether acetylsalicylic acid prophylaxis can prevent endotoxin tolerance, which is expressed as a decrease in pro-inflammatory cytokine levels between the first and second endotoxin challenge.

Study design:

Double-blind randomized placebo-controlled pilot study in 30 healthy male volunteers during repeated experimental endotoxemia. All subjects will receive a 14 day course of study medication (low-dose ASA or placebo) and undergo experimental endotoxemia (lipopolysacharide (LPS), E.Coli type O113) on day 7 and on day 14. LPS is administrated using an initial bolus of 1ng/kg followed by continuous infusion at 1ng/kg/hr during 3 hours.

Subjects are randomized in three study arms:

1. Treatment group: 7 days placebo / first endotoxemia / 7 days ASA 80 mg (loading dose on first day of 160mg) / second endotoxemia

2. Prophylaxis group: 7 days ASA 80 mg (loading dose on first day of 160mg) / first endotoxemia / 7 days ASA 80 mg / second endotoxemia

3. Placebo group: 7 days placebo / first endotoxemia / 7 days placebo / second endotoxemia


Recruitment information / eligibility

Status Completed
Enrollment 30
Est. completion date September 2017
Est. primary completion date December 2016
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Male
Age group 18 Years to 35 Years
Eligibility Inclusion Criteria:

- Written informed consent

- Age =18 and =35 yrs

- Male

- Healthy (as confirmed by medical history, examination, ECG, blood sampling)

Exclusion Criteria:

- Use of any medication

- Use of COX-inhibitors within 6 weeks prior to the first endotoxemia day

- Smoking

- Known anaphylaxis or hypersensitivity to acetylsalicylic acid or non-investigational products

- History or signs of atopic syndrome (asthma, rhinitis with medication and/or eczema)

- History of peptic ulcer disease

- History or signs of hematological disease

- Thrombocytopenia (<150*10^9/ml) or anemia (hemoglobin < 8.0 mmol/L)

- History of glucose-6-phosphate dehydrogenase deficiency

- History of intracranial hemorrhage

- History, signs or symptoms of cardiovascular disease, in particular:

- Previous spontaneous vagal collapse

- History of atrial or ventricular arrhythmia

- Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrioventricular block or a complete left 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 creatinine >120 µmol/l)

- Liver enzyme abnormalities (above 2x the upper limit of normal)

- Medical history of any disease associated with immune deficiency

- CRP > 20 mg/L, WBC > 12x109/L or < 4 x109/L or clinically significant acute illness, including infections, within 4 weeks before the first endotoxemia day

- Previous (participation in a study with) LPS administration

- Participation in a drug trial or donation of blood 3 months prior to first endotoxemia day

- Any vaccination within 3 months prior to first endotoxemia day until the end of the study

- Recent hospital admission or surgery with general anesthesia (<3 months to endotoxemia day)

- Use of recreational drugs within 21 days prior to the first endotoxemia day

- Inability to personally provide written informed consent (e.g. for linguistic or mental reasons) and/or take part in the study

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Aspirin

Placebo


Locations

Country Name City State
Netherlands Intensive Care Medicine, Radboud University Nijmegen Medical Centre Nijmegen Gelderland

Sponsors (1)

Lead Sponsor Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type Measure Description Time frame Safety issue
Primary Change in concentration plasma TNFalpha (pg/ml) measured with Luminex assay Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Change in concentration plasma IL-6 (pg/ml) measured with Luminex assay Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Change in concentration plasma IL-8 (pg/ml) measured with Luminex assay Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Change in plasma concentration of IL-10 (pg/ml) measured with Luminex assay Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Change in plasma concentration of IL-1RA (pg/ml) measured with Luminex assay Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Change in plasma concentration of IL-1beta (pg/ml) measured with Luminex assay Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Change in plasma concentration of MCP-1 (pg/ml) measured with Luminex assay Measured after the first and second LPS-challenge
Secondary Change in plasma concentration of MIP-1alpha (pg/ml) measured with Luminex assay Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Change in plasma concentration of MIP-1beta (pg/ml) measured with Luminex assay Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Change in monocytic HLA-DR expression (mHLA-DR) Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Change in symptoms during endotoxin day Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Change in blood pressure Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Change in temperature Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Change in heart rate Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Change in cerebral blood flow using Transcranial Doppler (TCD) measurements and Near Infrared Spectroscopy (NIRS) Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Arterial bloodgas Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Change in platelet monocyte complexes Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Change in monocyte surface antigen expression of PD-L1 Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Thromboxane B2 Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Prostaglandin E2 (PGE-M) Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Change in plasma enkephalin Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Kidney damage markers in urine (NGAL, KIM-1 and L-FABP) Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Change in leukocyte count (and differentiation) Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Change in transcriptional activity of leukocytes Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Change in plasma concentration of IFN-gamma (pg/ml) measured with Luminex assay Measured after the first and second LPS-challenge (on day 7 and day 14)
Secondary Change in lymphocyte surface antigen expression of PD-1 and IL7-RA Measured after the first and second LPS-challenge (on day 7 and day 14)
See also
  Status Clinical Trial Phase
Completed NCT04117802 - Effects of Maple Syrup on Gut Microbiota Diversity and Metabolic Syndrome N/A
Completed NCT01766414 - In Vivo Effects of C1-esterase Inhibitor on the Innate Immune Response During Human Endotoxemia - VECTOR II Phase 3
Completed NCT04130321 - Demonstration of the Prebiotic-like Effects of Camu-camu Consumption Against Obesity-related Disorders in Humans N/A
Completed NCT02612480 - Ticagrelor in Human Endotoxemia Response to Human Endotoxemia N/A
Completed NCT01474629 - Probiotic Sport Study N/A
Completed NCT00246714 - Pathophysiology and Clinical Relevance of Endotoxin Tolerance in Humans Phase 1
Recruiting NCT06147440 - Different Dietary Patterns N/A
Recruiting NCT03901807 - Safety and Efficacy of Polymyxin B Hemoperfusion (PMX) for Endotoxemic Septic Shock in a Randomized, Open-Label Study N/A
Completed NCT03754504 - Effects of Cranberry Powder Supplements on Gut Microbiota Diversity and Metabolic Syndrome N/A
Completed NCT03800277 - Effect of Cranberry and Agaves Extract on Microbiota and Intestinal Health N/A
Completed NCT00785018 - In Vivo Effects of C1-esterase Inhibitor on the Innate Immune Response During Human Endotoxemia N/A
Recruiting NCT00413348 - Type 2 Diabetes and the Effect of Probiotics N/A
Recruiting NCT00413465 - Study of Renal Blood Flow During Human Endotoxemia N/A
Completed NCT00412906 - Study of Gene Activity in Fat and Muscle in Diabetics and Healthy Controls N/A
Completed NCT05752968 - Elevated Levels of Antibodies to Endotoxin Core in Hemodialysis Patients With Peripheral Artery Disease
Completed NCT01374711 - The Effects of Immunostimulation With GM-CSF or IFN-y on Immunoparalysis Following Human Endotoxemia N/A
Completed NCT00916448 - The Effects of Atazanavir-induced Hyperbilirubinemia During Human Endotoxemia N/A
Completed NCT00332267 - Cerebral Blood Flow and Metabolism During Hypoxia and Endotoxemia N/A
Completed NCT03482284 - Effect of Monosaccharides on Intestinal Barrier Function N/A
Completed NCT03972878 - Foodprint 1.0: Physiological Acute Responses After Consumption of Confectionary Products N/A