Primary ObjectiveTo investigate changes of CSF proteins over time using continuous CSF sampling for 36 hours, including but not limited to A*1/x-42, A* 1/x-40, A* 1/x-38 and A* 1/x-37 in subjects with MCI or AD. Secondary Objectives1. To investigate…
ID
Source
Brief title
Condition
- Mental impairment disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Difference in 36-hour course of different proteins in cerebrospinal fluid
between healthy elderly subjects and patients with Alzheimer's disease or Mild
Cognitive Impairment
Secondary outcome
- difference in 36-hour course of proteins in cerebrospinal fluid in healthy
elderly subjects, between groups with and without treatment with an
anti-inflammatory marker
- difference in 36-hour course of proteins in cerebrospinal fluid in healthy
elderly subject, between a group in which sampeling starts immediately, and a
group in which sampeling starts later
Tolerability:
o adverse events
o vital signs
o safety laboratory
Background summary
For the development of new therapies targeting Alzheimer*s Disease (AD),
changes of A* and/or tau are key biomarkers in discovery and potentially in
clinical trials. While in preclinical studies direct measurement in the brain
is possible, this is not a routine option in clinical trials. In contrast CSF,
sharing the same environment, will be the best proxy to understand changes upon
therapy. When not measuring directly in the brain, at the site of the
pathological changes and potential therapeutic interventions, but more distant,
a potential effect will be diluted and as such less pronounced. Therefore, it
is crucial to optimize and understand the technique of CSF sampling and
measurement of CSF proteins, to base decisions on reliable data in phase 1,
proof-of-mechanism studies, for therapies targeting A*.
In this study the changes in CSF proteins over 36 hours after lumbar
introduction of a spinal catheter and the reasons for the less pronounced
increase in A*1-42 as seen in the previous studies will be investigated. The
analytes will include, but may not be limited to A* 1/x-42, A* 1/x-40, A*
1/x-38, and A* 1/x-37 in elderly healthy subjects and subjects with Mild
Cognitive Impairment (MCI) or AD. Part A of the study, CSF sampling in elderly
healthy subjects is already performed.
Study objective
Primary Objective
To investigate changes of CSF proteins over time using continuous CSF sampling
for 36 hours, including but not limited to A*1/x-42, A* 1/x-40, A* 1/x-38 and
A* 1/x-37 in subjects with MCI or AD.
Secondary Objectives
1. To investigate the safety and tolerability of continuous CSF sampling in
subjects with MCI or AD;
2. To investigate the effects of sampling frequency on changes of CSF proteins
over time using continuous CSF sampling in elderly healthy subjects; and
3. To investigate the effect of an anti-inflammatory agent (Ibuprofen) on
possible changes of CSF proteins over time using continuous CSF sampling in
elderly healthy subjects.
Study design
This is an open-label, randomized, biomarker study without investigational
medicinal product in subjects with MCI or Alzheimer*s disease.
The study will consist of an eligibility screening examination (between 21 and
2 days prior to spinal catheter insertion), an inpatient CSF
collection/measurement period (day -1 to day 3), and a follow-up examination
(approximately 7 to 14 days after removal of the catheter).
For assessment schedule see flow chart.
Study burden and risks
The risk of participation includes the possible side-effects from the spinal
catheter (for example headache, low bloodpressure, nausea and dizziness) and
findings during test (i.e. positive test result for hepatitis B, hepatitis C or
HIV).
No serious side effects are expected.
Experience with cerebrospinal fluid sampeling in patients with Alzheimer's
disease or Mild Cognitive Impairment, and de development of a biomarker
platform in Alzheimer's, could contribute to a reliable evalutation of the
efficacy of new drugs for the treatment of Alzheimer's disease.
Turnhoutseweg 30
Beerse 2340
BE
Turnhoutseweg 30
Beerse 2340
BE
Listed location countries
Age
Inclusion criteria
o Diagnosis of probable or possible AD (according to NINCDS-ADRDA)
o Mini Mental State Exam score of *18 at screening
o Signed informed consent, and subjects must have signed a separate written informed consent indicating willingness to participate in Part 1 genetic testing (required), and indicate either consent or refusal for Part 2 DNA storage (optional)
o Mentally capable of understanding the implications of study participation
o For MCI subjects only: biological evidence for AD (evidenced by hippocampal atrophy on MRI, positive PIB scan or a positive AD CSF biomarker pattern based on changes on A* (decrease), t-tau and p-tau (increase)
Exclusion criteria
o Clinically significant abnormal physical- or neurological examination (including fundoscopy), vital signs or 12-lead ECG at screening.
o Has a relevant history of lower back pain or scoliosis and/or major (lumbar) back surgery (microdiscectomy is allowed).
o Relevant history of or current neurological disease other than AD/MCI (including any history of postdural puncture headache).
o History of epilepsy or fits or unexplained black-outs.
o History or family history of abnormal bleeding or of blood clotting
o History of spontaneous, prolonged or severe bleeding with unclear origin.
o Positive screen for drugs or alcohol
o Current anemia
o Allergic to local anesthetics and/or chlorhexidine.
o Inability to refrain from
- Low Molecular Weight Heparin (LMWH) treatment within 12 hours prior to spinal
- Other anticoagulant treatment (besides LMWH described above) within 1 week prior to spinal catheter insertion.
- Aspirin treatment (even low dose) within 5 days prior to spinal catheter insertion.
o At pre-check:
- Topical infection or local dermatological condition at the puncture site prior to puncture (pre-puncture Day 1).
- Clinically significant acute illness within 7 days prior to the study
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL40311.029.12 |