Doxycycline in early CJD: a double-blinded randomised phase II and observational study

J Neurol Neurosurg Psychiatry. 2017 Feb;88(2):119-125. doi: 10.1136/jnnp-2016-313541. Epub 2016 Nov 2.

Abstract

Objectives: 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.

Trial registration number: EudraCT 2006-003934-14; Results.

Publication types

  • Clinical Trial, Phase II
  • Observational Study
  • Randomized Controlled Trial

MeSH terms

  • Age of Onset
  • Aged
  • Anti-Bacterial Agents / therapeutic use*
  • Creutzfeldt-Jakob Syndrome / drug therapy*
  • Double-Blind Method
  • Doxycycline / therapeutic use*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Survival Rate
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Doxycycline