Healthy volunteers Other
Conditions
Interventions
An open-label study to evaluate the effects of the single dose (either 1 or 2 ng/kg) of iv lipopolysaccharide (LPS) challenge on the bone marrow immune compartment.
LPS, purified lipopolysaccharide p
Sponsors
Centre for Human Drug Research
Eligibility
Sex/Gender
Male
Age
18 Years to 35 Years
Inclusion criteria
Inclusion criteria: 1. Male participants between 18 and 35 years of age (inclusive), at the time of signing the informed consent 2. Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and ECG 3. A body mass index (BMI) between 18.0 and 30.0 kg/m2 (inclusive), and a minimum body weight of 50 kg 4. Able to give written informed consent and willing to comply with all study-related procedures
Exclusion criteria
Exclusion criteria: 1. Clinically significant abnormalities, as judged by the investigator, in test results (including physical examination, laboratory tests, ECG and vital signs) 2. History of medical conditions, which in the opinion of the investigator may compromise the participant’s safety or the scientific value of the study, posing an unacceptable risk to the participant or interfering with the participant's ability to comply with study procedures or abide by study restrictions 3. History of trauma with likely damage to the spleen or surgery to the spleen, or history of hip fracture or surgery in the pelvic area 4. Previous participation in a systemic (i.v./inhaled) LPS challenge trial within a year before the first study day 5. Any active inflammatory or infectious disease (e.g., periodontitis), with the exception of common viral or fungal skin infections such as plantar warts or athlete’s foot 6. Febrile illness within 30 days before the start of the first study day 7. Antibiotic use, operation or intervention by surgeon/dentist within one month before the first study day 8. Hemorrhagic diathesis (easy bruising, epistaxis, gastrointestinal bleeding, history of serious bleeding) 9. Clinically significant hypertension (defined as systolic blood pressure > 145 mmHg or diastolic blood pressure >90 mmHg, repeatedly measured after 5 minutes in resting supine position), or clinically significant hypotension(defined as systolic blood pressure 120ms, PR interval > 210ms, QTcFinterval > 470ms) 11. Positive test results for hepatitis B, hepatitis C, HIV antibody or any other obvious disease associated with immune deficiency 12. Subjects with a positive urine drug screen/alcohol test result at screening or first admission or a history of substance abuse in the last 12 months prior to the start of the study 13. Subjects who smoke more than 6 cigarettes or the equivalent of tobacco per day and are unwilling to abstain from smoking during the study period (from screening until EOS) 14. Loss or donation of blood over 500 mL within 3 months prior to screening or donation of plasma within 14 days prior to screening 15. Participation in an investigational drug or device study within 3 months between the last dosing in the previous study and admission to the CRU in the present study or more than 4 times in the past year 16. Any vaccination within the last 3 months; COVID-19 vaccination (or infection as confirmed by a PCR test) is allowed up until 4 weeks prior to admission to the CRU; COVID-19 booster vaccination is allowed up until 2 weeks prior to admission to the CRU
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Safety and tolerability (vital signs, weight and height, physical examination, ECG, safety laboratory assessments) measured using standard techniques. For vital signs, weight and height performed at Screening, Day 1 (-1h, 1h, 6h), Day 7/8 (-2h, 1h, 2h, 6h, 24h), Follow-up; Physical examination performed at Screening, Day 1 (6h), Day 7/8 (-2h, 24h) and Follow-up; Safety laboratory assessments performed at Screening, Day 1 (-1h), Day 7/8 (4h), Follow-up 2. Pain measured using the Visual Analogue Scale at Day 1 (-1h, 0h, 1h, 6h), Day 7/8 (03h, 1h, 2h, 4h, 6h, 24h) and at Follow-up 3. Effects of the intravenous lipopolysaccharide (LPS) challenge model in bone-marrow aspiration and biopsies measured using immunophenotyping, cytomorphology and immunohistology at baseline and 4h post-LPS 4. Effects of the LPS challenge model measured using whole-blood immunophenotyping and cytokine measurement at baseline and 4h post-LPS 5. Immune cell expression profile in whole blood and blood marrow samples measured RNA-sequencing at baseline and 4h post-LPS 6. Feasibility measured using a Subject Experience Questionnaire at Follow-up | — |
Secondary
| Measure | Time frame |
|---|---|
| There are no secondary outcome measures | — |
Countries
Netherlands
Contacts
Public ContactIgor Radanovic
Outcome results
None listed