TORNA ALL’ELENCO

Doxycycline in Creutzfeldt-Jakob disease: A phase 2, randomized, double-blind, placebo-controlled trial in Prion

2013
ASL Città di Torino

Tipo pubblicazione

Conference Abstract

Autori/Collaboratori (19)Vedi tutti...

Tagliavini F
IR CCS Foundation Carlo Besta Neurological Institute, Milano, Italy
Forloni G
Mario Negri Institute for Pharmachological Research, Milano, Italy
Haik S
Inserm; U 975, Paris, France

et alii...

Abstract

Introduction. At present, there is no effective treatment to modify the course of Creutzfeldt-Jakob disease (CJD). Tetracyclines were found to bind amyloid fibrils of different composition, including PrP, and to reduce infectivity of prion-infected brains. Among tetracyclines, doxycycline (1) interacts with and revert the protease- resistance of PrPSc extracted from brain tissue of patients with all forms of CJD, (2) reduces the infectivity titer in prion-contaminated material and (3) prolongs survival of experimentally prion-infected animals. On this ground, a series of CJD patients in Italy and Germany received compassionate treatment with doxycycline at a daily oral dose of 100 mg from the time of diagnosis to death. The results of these open trials showed an increase in survival time in doxycycline-treated patients compared with historical series. This result prompted Italian and French CJD care systems to carry out a randomized, double-blind study of doxycycline vs. placebo with the primary objective to evaluate its effectiveness in increasing survival time in patients with CJD. Materials and Methods. In both countries we included patients with a probable diagnosis of sporadic CJD and patients with genetic forms due to E200K mutation in France and E200K and V210I mutation in Italy, because of a clinical phenotype indistinguishable from that of sporadic CJD. Enrolled subjects were treated orally with 100 mg doxycycline per day or with identical placebo under double-blind conditions from the day of randomization to death. The primary efficacy variable was the survival time from the day of randomization. Patient and his family were informed on the protocol and a signed consent was obtained. The study was approved by the Ethics Committees of Carlo Besta Institute and the other involved Italian centers, and the Pitié-Salpêtrière Hospital. Results. We randomized 121 individuals (55 in Italy and 66 in France). Of these patients, 62 were assigned to the treat

Keywords

brain; phenotype; professional standard; brain tissue; hospital; gender; codon; survival; Germany; prion disease; open study; double blind procedure; France; mutation; randomization; diagnosis; death; infection; Italy; survival time; prion; patient; controlled study; human; Creutzfeldt Jakob disease; proteinase; amyloid; trichloroethylene; tetracycline derivative; placebo; doxycycline;