PMID- 23143156
OWN - NLM
STAT- MEDLINE
DCOM- 20131119
LR  - 20211021
IS  - 1432-1041 (Electronic)
IS  - 0031-6970 (Linking)
VI  - 69
IP  - 5
DP  - 2013 May
TI  - Serial CSF sampling over a period of 30 h via an indwelling spinal catheter in 
      healthy volunteers: headache, back pain, tolerability and measured acetylcholine 
      profile.
PG  - 1083-90
LID - 10.1007/s00228-012-1443-y [doi]
AB  - BACKGROUND/AIM: Timed interval cerebrospinal fluid (CSF) sampling by indwelling 
      catheterization can be a valuable corroborative tool for the pharmacokinetic and 
      pharmacodynamic assessment of drugs. CSF sampling in studies on drug candidates 
      for Alzheimer's disease have been conducted in evaluations of the biomarkers 
      acetylcholine (ACh), tau proteins, amyloid precursor protein and beta-amyloid 
      fragments. The primary aim of this study was to study the feasibility and the 
      burden on the healthy volunteers of serial CSF sampling within the contract 
      research organization environment in order to establish a standardized research 
      tool for future drug development studies. MATERIALS AND METHODS: This study is a 
      validation study in healthy subjects: eight healthy male subjects aged 55-75 
      years were enrolled. After eligibility had been confirmed, the subjects were 
      admitted to the clinical pharmacology unit 2 days before starting the CSF 
      sampling procedure. Hydration by drip infusion of 2 L saline was performed for 24 
      h before starting the CSF sampling procedure, and for antithrombotic purposes, 
      Fraxiparine (nadroparine calcium) was given 12 and 36 h after intradural 
      catheterization. CSF catheterization was performed by board-certified 
      anesthesiologists with experience in inserting indwelling intrathecal catheters. 
      Subjects only required to remain in a horizontal position for the first 24 h 
      after removal of the catheter. CSF and blood samples were collected by interval 
      sampling over a 30-h period. RESULTS: The study was completed by seven of the 
      eight subjects. Six subjects who completed the study reported adverse effects 
      (AEs) which were all mild and from which they recovered during their stay in the 
      clinic. A total of 25 AEs were reported of which 13 were considered to be 
      procedure-related. The procedure was well tolerated by all participating 
      subjects, and the VAS scale scores for headache and back pain were low. CSF 
      samples were analyzed for ACh. All values were above the lowest limit of 
      quantification. On average, the ACh concentration started at a low level but rose 
      between 1 and 2 h after insertion of the catheter and then remained high during 
      the whole sampling period up to 30 h. CONCLUSION: Serial sampling of CSF in seven 
      healthy volunteers up to 30 h occurred without serious complications and was well 
      tolerated. The CSF collected was of good quality and facilitated the assessment 
      of an Alzheimer's disease-sensitive biomarker. We conclude that this validation 
      study can form the basis for future patient studies aimed at elucidating disease 
      mechanisms and the pharmacodynamics of drugs in the developmental stage.
FAU - den Daas, Izaak
AU  - den Daas I
AD  - QPS Netherlands BV, Groningen, The Netherlands. izaak.den.daas@qps.com
FAU - Wemer, Johan
AU  - Wemer J
FAU - Abou Farha, Khalid
AU  - Abou Farha K
FAU - Tamminga, Wim
AU  - Tamminga W
FAU - de Boer, Theo
AU  - de Boer T
FAU - Spanjersberg, Rob
AU  - Spanjersberg R
FAU - Struys, Michel M R F
AU  - Struys MM
FAU - Absalom, Anthony R
AU  - Absalom AR
LA  - eng
PT  - Journal Article
PT  - Validation Study
DEP - 20121110
PL  - Germany
TA  - Eur J Clin Pharmacol
JT  - European journal of clinical pharmacology
JID - 1256165
RN  - 0 (Biomarkers)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/*cerebrospinal fluid
MH  - Aged
MH  - *Back Pain
MH  - Biomarkers/cerebrospinal fluid
MH  - Catheters, Indwelling/*adverse effects/microbiology
MH  - *Headache
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Patient Satisfaction
MH  - Spinal Cord/*metabolism/surgery
EDAT- 2012/11/13 06:00
MHDA- 2013/11/20 06:00
CRDT- 2012/11/13 06:00
PHST- 2012/06/15 00:00 [received]
PHST- 2012/10/24 00:00 [accepted]
PHST- 2012/11/13 06:00 [entrez]
PHST- 2012/11/13 06:00 [pubmed]
PHST- 2013/11/20 06:00 [medline]
AID - 10.1007/s00228-012-1443-y [doi]
PST - ppublish
SO  - Eur J Clin Pharmacol. 2013 May;69(5):1083-90. doi: 10.1007/s00228-012-1443-y. 
      Epub 2012 Nov 10.