Method Development Cerebrospinal fluid clearance
Conditions
Interventions
Participants will be randomized to receive the intervention to no intervention
in a 1:1 ratio (HFCWO to no HFCWO).
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Signed informed consent prior to any study-mandated procedure 2. Healthy male or female subjects, 18 to 50 years of age, inclusive at screening. 3. Body mass index (BMI) between 18 and 30 kg/m2, inclusive at screening, and with a minimum weight of 50 kg. 4. All women of childbearing potential must practice effective contraception during the study. 5. Has the ability to communicate well with the Investigator in the Dutch language and willing to comply with the study restrictions.
Exclusion criteria
Exclusion criteria: 1. Evidence of any active or chronic disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator (following a detailed medical history, physical examination, vital signs (systolic and diastolic blood pressure, pulse rate, body temperature) and 12-lead electrocardiogram (ECG)). Minor deviations from the normal range may be accepted, if judged by the Investigator to have no clinical relevance. 2. Clinically significant abnormalities, as judged by the investigator, in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis). In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy subjects. 3. History of malignancy not deemed cured by their treating physician. 4. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening. 5. Systolic blood pressure (SBP) greater than 140 or less than 90 mm Hg, and diastolic blood pressure (DBP) greater than 90 or less than 50 mm Hg at screening. 6. Abnormal findings in the resting ECG at screening defined as: a. QTcF> 450 or 470 or 100 bpm) c. Personal or family history of congenital long QT syndrome or sudden death; d. ECG with QRS and/or T wave judged to be unfavourable for a consistently accurate QT measurement (e.g., neuromuscular artefact that cannot be readily eliminated, arrhythmias, indistinct QRS onset, low amplitude T wave, merged T- and U-waves, prominent U waves); e. Evidence of atrial fibrillation, atrial flutter, complete branch block, Wolf-Parkinson-White Syndrome, or cardiac pacemaker 7. Participation in an investigational drug or device study (last dosing of previous study was within 90 days prior to first dosing of this study) 8. History of abuse of addictive substances (alcohol, illegal substances) or current use of more than 21 units alcohol per week, drug abuse, or regular user of sedatives, hypnotics, tranquillisers, or any other addictive agent 9. Positive test for drugs of abuse at screening. A retest may be performed at the discretion of the investigator. 10. Alcohol will not be allowed from at least 24 hours before each visit, including screening and follow-up 11. Smoker of more than 10 cigarettes per day prior to screening or who use tobacco products equivalent to more than 10 cigarettes per day and unable to abstain from smoking whilst in the unit. 12. Is demonstrating excess in caffeine consumption (more than eight cups of coffee or equivalent per day) 13. Loss or donation of blood over 500 mL within three months (males) or four months (females) prior to screening or intention to donate blood or blood products during the study. 14. If a woman, pregnant, or breast-feeding, or planning to become pregnant during the study. 15. For CSF sampling, any of the criteria below: a. History of clinically significant hypersensitivity to local anesthetics that may
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • Change in neurofilament light chain • Change in amyloid beta • Change in tau • Change in total amount of neural derived exosomes. | — |
Secondary
| Measure | Time frame |
|---|---|
| n.a. | — |
Countries
Netherlands
Outcome results
None listed