NR AOUR
AU Kennedy,A.M.; Walker,S.; Darbyshire,J.; Collinge,J.
TI The MRC PRION-1 trial: development of a protocol to evaluate quinacrine and other potential therapeutics for human prion disease
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-115
PT Konferenz-Poster
AB The Department of Health and the MRC are supporting the development of a UK Trial Centre to assess existing and future drug treatments for prion disease. National referral guidelines are being framed. The PRION-1 protocol describes a partially randomised controlled patient preference trial to evaluate quinacrine in all types of human prion disease. Patients will be placed into three groups according to preference and willingness to be randomised, but will follow the same schedule of evaluations. The primary aim is a randomised controlled comparison of immediate open-label quinacrine versus no quinacrine with the option of starting open-label quinacrine after 24 weeks, patients who are willing to be randomised will enter this comparison. Some patients will have a strong preference for receiving quinacrine immediately; these will therefore enter an uncontrolled open label study of quinacrine. Other patients will have a strong preference for not receiving quinacrine will be followed up in an uncontrolled study of natural history. The primary efficacy endpoints are mortality and the proportion of responders overall and at 24 weeks. Response is defined as lack of deterioration on all of (1) the digital video of the neurological exam (2) the Clinician's Interview Based Impression of Change (CIBIC-plus), and (3) the Brief Psychiatric Rating Scale (BRPS). Secondary efficacy endpoints are neurological and neuropsychological changes, including MRI, EEG and neurological assessments. 10 patients have been enrolled in a pilot study for PRION-1 (1 sporadic, 3 variant and 6 inherited). The mean MMSE for the 10 enrolled patients was 16 (range 5 to 25). To 31 March 2003, the median follow up on study was 20 weeks (range 0 to 69), and 4 patients had died at 16, 20, 69 and 44 weeks respectively. 5 individuals had dose modifying liver toxicity, and 3 experienced a dose-modifying rash. All patients had had CIBIC, Rankin and CDR were 90% complete. The ADAS-COG was performed on 6 patients at baseline and only 4 were able to repeat this test subsequently. Serial MRI scans were obtained in 7 patients.
AD A.M. Kennedy, J. Collinge, National Prion Clinic, St Mary's Hospital, London and MRC Prion Unit, London, UK; S. Walker, J. Darbyshire, MRC Clinical Trials Unit, University College London, UK
SP englisch
PO Deutschland