A prospective, methodology study to identify potential biomarkers of myelin dynamics in CSF using metabolic labeling with stable isotopes in healthy volunteers

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 6

Inclusion Criteria

- Signed informed consent prior to any study-mandated procedure;
- Males or females, aged 18-70 years;
- BMI between: 18-30 kg/m2, minimal weight 50 kg
- Ability to communicate well with the investigator in the Dutch language.
- Ability to easily visit CHDR in Leiden oncea week
- Expected compliance to the protocol with respect to drinking D2O 2 times every day for 70 days

Exclusion Criteria

- 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 case of uncertain or questionable results, tests performed during screening may be repeated before the first occasion to confirm eligibility or judged to be clinically irrelevant.
- Subject is pregnant or breastfeeding.
- Any contraindication for a lumbar puncture.
- Recent (within 60 days) or current use of medications.
- Participation in a clinical trial within 90 days of screening or more than 4 times in the previous year.
- Positive test for drugs of abuse at screening or pre-dose.
- Alcohol is prohibited from 24 hours before screening and the first visit.
- History or symptoms of any significant disease including (but not limited to) neurological, psychiatric, endocrine, cardiovascular, respiratory, gastrointestinal, hepatic, or renal disorder.
- Positive hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening.
- Donation of blood over 500 mL within 3 months prior to screening.
- Unwillingness or inability to comply with the study protocol for any other reason.

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Fractional synthesis rate of galactosylceramide (fGalC)</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>• Fractional synthesis rate of sulfatide (fSulft).<br /><br>• Percentage D2O enrichment in body water as determined in urine and plasma.<br /><br>• (Myelin) lipid and proteins markers in plasma samples.<br /><br>• Total concentration of galactosylceramide and sulfatide in the CSF.<br /><br><br /><br>Safety/tolerability endpoints:<br /><br>• AEs leading to premature discontinuation of D2O.<br /><br>• Treatment-emergent (S)AEs up to 5 half-lives after D2O discontinuation.<br /><br>• Change from baseline to end-of-study in vital signs: blood pressure and heart<br /><br>rate.<br /><br>• Treatment-emergent ECG abnormalities up to 5 half-lives after D2O<br /><br>discontinuation.<br /><br>• Treatment-emergent marked laboratory abnormalities up to 5 pharmacokinetic<br /><br>half-lives after D2O discontinuation</p><br>