Doxycycline in early CJD: a double-blinded randomised phase II and observational study.
OBJECTIVE
The main objective of the present study is to study the therapeutic efficiency of doxycycline in a double-blinded randomised phase II study in a cohort of patients with sporadic Creutzfeldt-Jakob disease (sCJD).


METHODS
From the National Reference Center of TSE Surveillance in Germany, patients with probable or definite sCJD were recruited for a double-blinded randomised study with oral doxycycline (EudraCT 2006-003934-14). In addition, we analysed the data from patients with CJD who received compassionate treatment with doxycycline in a separate group. Potential factors which influence survival such as age at onset, gender, codon 129 polymorphism and cognitive functions were evaluated. The primary outcome measure was survival.


RESULTS
Group 1: in the double-blinded randomised phase II study, 7 patients in the treatment group were compared with 5 controls. Group 2: 55 patients with sCJD treated with oral doxycycline were analysed and compared with 33 controls by a stratified propensity score applied to a Cox proportional hazard analysis. The results of both studies were combined by means of a random-effects meta-analysis. A slight increase in survival time in the doxycycline treatment group was observed (p=0.049, HR=0.63 (95% CI 0.402 to 0.999)).


CONCLUSIONS
On the basis of our studies, a larger trial of doxycycline should be performed in persons in the earliest stages of CJD.


BACKGROUND
EudraCT 2006-003934-14; Results.
Department of Neurology, National Reference Center for TSE Surveillance, University Medical Center Goettingen, Göttingen, Germany.
Daniela
D
Varges
Department of Neurology, National Reference Center for TSE Surveillance, University Medical Center Goettingen, Göttingen, Germany.
Henrike
H
Manthey
Department of Neurology, National Reference Center for TSE Surveillance, University Medical Center Goettingen, Göttingen, Germany.
Uta
U
Heinemann
Department of Neurology, National Reference Center for TSE Surveillance, University Medical Center Goettingen, Göttingen, Germany.
Claudia
C
Ponto
Department of Neurology, National Reference Center for TSE Surveillance, University Medical Center Goettingen, Göttingen, Germany.
Matthias
M
Schmitz
Department of Neuropathology, University Medical Center Goettingen, Göttingen, Germany.
Walter J
WJ
Schulz-Schaeffer
Department of Neurology, National Reference Center for TSE Surveillance, University Medical Center Goettingen, Göttingen, Germany.
Anna
A
Krasnianski
Department of Neurology, National Reference Center for TSE Surveillance, University Medical Center Goettingen, Göttingen, Germany.
Maren
M
Breithaupt
Department of Neurology, National Reference Center for TSE Surveillance, University Medical Center Goettingen, Göttingen, Germany.
Fabian
F
Fincke
Department of Medical Statistics, University Medical Center Goettingen, Göttingen, Germany.
Katharina
K
Kramer
Department of Medical Statistics, University Medical Center Goettingen, Göttingen, Germany.
Tim
T
Friede
Department of Neurology, National Reference Center for TSE Surveillance, University Medical Center Goettingen, Göttingen, Germany.
Inga
I
Zerr
D017668:Age of Onset; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D007562:Creutzfeldt-Jakob Syndrome / Q000188:drug therapy*; D004311:Double-Blind Method; D004318:Doxycycline / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D004318:Doxycycline