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Research paper
Doxycycline in early CJD: a double-blinded randomised phase II and observational study
  1. Daniela Varges1,
  2. Henrike Manthey1,
  3. Uta Heinemann1,
  4. Claudia Ponto1,
  5. Matthias Schmitz1,
  6. Walter J Schulz-Schaeffer2,
  7. Anna Krasnianski1,
  8. Maren Breithaupt1,
  9. Fabian Fincke1,
  10. Katharina Kramer3,
  11. Tim Friede3,
  12. Inga Zerr1
  1. 1Department of Neurology, National Reference Center for TSE Surveillance, University Medical Center Goettingen, Göttingen, Germany
  2. 2Department of Neuropathology, University Medical Center Goettingen, Göttingen, Germany
  3. 3Department of Medical Statistics, University Medical Center Goettingen, Göttingen, Germany
  1. Correspondence to Professor Inga Zerr, National Reference Center for TSE Surveillance, Clinical Dementia Center, Department of Neurology, University Medical Center, Robert-Koch Str. 40, Göttingen D-37075, Germany; ingazerr{at}med.uni-goettingen.de

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.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Contributors DV was involved in study concept and design, and editing the manuscript. HM, CP, WJS-S, AK, MB and FF were involved in acquisition of data. UH was involved in study concept and acquisition of data. MS was involved in critical revision of the manuscript. KK and TF were involved in statistical analyses and critical revision of the manuscript. IZ was involved in study concept and supervision, and funding.

  • Funding This study was supported by the Federal Ministry of Education and Research (grant no. 01KG0905) and by the Robert Koch-Institute through funds from the Federal Ministry of Health (grant no. 1369-341). Some of the work by KK has received funding from FP HEALTH 2013 ‘Innovative methodology for small populations research’ (InSPiRe) grant no. 602144.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Ethikkommitee University of Goettingen.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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