Gram negative infection, Sepsis, Lipopolysaccharide, SRT21040, Sirtuins, innate immunity
Conditions
Interventions
This study consists of three treatment arms (N = 8 per arm). Subjects in arm one will receive once daily doses of SRT2104 (2.0 g/day) for seven consecutive days. Subjects in arm two will receive once
4 ng/kg body weight). LPS will be given 3 hours after dosing.
Sponsors
Academic Medical Center (AMC), Center of Experimental Molecular Medicine
Eligibility
Inclusion criteria
Inclusion criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply: 1. Healthy, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination and laboratory tests carried out within 28 days prior to day 1. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures; 2. Male between 18 and 35 years of age inclusive, at the time of signing the informed consent; 3. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form; 4. No history of HIV 1 and 2, and hepatitis B and C; 5. Normal 12 lead ECG without any clinically significant abnormality as judged by the Investigator and average QTcB or QTcF < 450 msec; 6. Normal renal and liver function (normal serum creatinine and liver function tests (ALT, AST, Total bilirubin, alkaline phosphatase); 7. Subjects must agree with their partners to use double-barrier birth control or abstinence while participating in the study and for 12 weeks following the last dose of study drug.
Exclusion criteria
Exclusion criteria: 1. Known diseases; 2. A history of smoking within the last six months, or regular consumption of greater than three units of alcohol per day; 3. Administration of any investigational drug within 30 days of study initiation; 4. Donation of blood within 60 days, or loss of greater than 400 ml of blood within 12 weeks of study initiation; 5. History of enhanced bleeding tendency; 6. History of heparin-induced thrombocytopenia; 7. History of serious drug-related reactions, including hypersensitivity.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary study endpoints include clinical signs and symptoms and laboratory parameters for inflammation (cytokines, activation of leukocytes, coagulation and vascular endothelium). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints include pharmacokinetics and safety recordings. Exploratory endpoints include lipid profiles, acute phase proteins, metabolic profiles and gene expression analysis from white blood cells. | — |
Contacts
Public ContactAnne Jan Meer, van der
Academic Medical Center, University of Amsterdam Center of Experimental and Molecular Medicine Meibergdreef 9, Room G2-130
Outcome results
None listed