Early Stage Clinical

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

In Psychiatry and Neurology, serial cerebrospinal fluid (CSF) sampling can yield important information on neuropeptides, neurotransmitters and metabolites. Comparing levels of these biomarkers with pharmacokinetic data can help evaluate medicinal interventions during drug development. Obtaining quality CSF samples to test, however, poses some technical challenges.

QPS clinicians Izaak den Daas, Johan Wemer, Khalid Abou Farha and Wim Tamminga co-reported a validation study of healthy volunteers to assess the feasibility, safety and tolerability of serial CSF sampling. Their goal was to establish a standard procedure to guide timed interval CSF sampling via an indwelling catheter, for application in future drug development studies. At the same time, they wanted to establish that this methodology produced usable CSF samples.

For the study, seven healthy male subjects aged 55–75 years were intravenously pre-hydrated. Experienced, board-certified anesthesiologists inserted indwelling intrathecal catheters. Blood and CSF samples were collected over 30 hours, and subjects were given the antithrombotic Fraxiparine 12 and 36 hours after catheterization. After removal of the catheter, subjects were kept lying down for 24 hours. Side effects were assessed by a series of questionnaires and by exit interviews.

In general, subjects tolerated the procedure well, scoring low on the VAS (Visual Analog Scale) for headache and back pain. Reported adverse effects were mild and resolved before subjects left the clinic. Furthermore, all CSF samples tested reflected non-negligible levels of Acetylcholine, an Alzheimer’s Disease-sensitive biomarker, indicating that the CSF collected was of good quality.

Since the procedure resulted in no serious complications, was well-tolerated, and produced high quality CSF samples, the authors concluded that their validation study could form the basis for future patient studies requiring serial CSF sampling to investigate disease mechanisms and the pharmacodynamics of developmental drugs.

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

back
top
20 years in pharma R&D navigation