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Doxycycline in Creutzfeldt-Jakob disease: a phase 2, randomised, double-blind, placebo-controlled trial


Haïk, Stéphane, Marcon, Gabriella, Mallet, Alain, Tettamanti, Mauro, Welaratne, Arlette, Giaccone, Giorgio, Azimi, Shohreh, Pietrini, Vladimiro, Fabreguettes, Jean-Roch, Imperiale, Daniele, Cesaro, Pierre, Buffa, Carlo, Aucan, Christophe, Lucca, Ugo, Peckeu, Laurène, Suardi, Silvia, Tranchant, Christine, Zerr, Inga, Houillier, Caroline, Redaelli, Veronica, Vespignani, Hervé, Campanella, Angela, Sellal, François, Krasnianski, Anna, Seilhean, Danielle, Heinemann, Uta, Sedel, Frédéric, Canovi, Mara, Gobbi, Marco, Di Fede, Giuseppe, Laplanche, Jean-Louis, Pocchiari, Maurizio, Salmona, Mario, Forloni, Gianluigi, Brandel, Jean-Philippe, Tagliavini, Fabrizio


The Lancet. Neurology, Volume: 13, No.: 2, Pages.: 150-158

Year of Publication



Background: Creutzfeldt-Jakob disease (CJD) is a fatal, untreatable prion encephalopathy. Previous studies showed that doxycycline is effective in in-vitro and in-vivo models of disease, and patients with CJD who received compassionate treatment with doxycycline showed increased survival time compared with historical series. We therefore did a randomised, double-blind study of doxycycline versus placebo in CJD.; Methods: We recruited patients older than 18 years old who had a diagnosis of definite or probable sporadic CJD or genetic forms of the disease via Italian reference centres and the French national referral system. Patients were randomly assigned (ratio 1:1) to receive oral doxycycline (100 mg daily) or placebo under double-blind conditions from the day of randomisation to death. Centralised randomisation was done independently of enrolment or evaluation of patients using a minimisation method in Italy and a simple randomisation in France. Participants, caregivers, and clinicians were masked to group assignment. The primary efficacy variable was the survival time from randomisation. Interim analyses were planned to detect a significant effect of treatment as early as possible. This trial is registered with EudraCT, 2006-001858-27 for the Italian study and 2007-005553-34 for the French study.; Findings: From April 12, 2007, to Aug 19, 2010, in Italy, and from Jan 30, 2009, to Jan 10, 2012, in France, 121 patients with CJD were enrolled in the study, 62 of whom were randomly assigned to the treatment group and 59 to the placebo group. The first interim analysis showed absence of superiority of doxycycline compared with placebo, and the trial was stopped for futility. Efficacy analyses did not show significant differences between patients treated with doxycycline and placebo with regard to survival times (HR 1.1, 95% CI 0.8-1.7, p=0.50). Serious adverse events were judged not to be related to treatment, whereas a relation was deemed probable or possible for five non-serious adverse events that occurred in each treatment group.; Interpretation: Doxycycline at a dose of 100 mg per day was well tolerated but did not significantly affect the course of CJD, at variance with the results of previous observational studies. Our experience could be useful in the design of large multinational controlled trials of potential anti-prion molecules in this rare disease.; Funding: Agenzia Italiana Farmaco, Italian Ministry of Health, AIEnP, and French Ministry of Health.; Copyright © 2014 Elsevier Ltd. All rights reserved.

Bibtex Citation

@article{Ha_k_2014, doi = {10.1016/s1474-4422(13)70307-7}, url = {}, year = 2014, month = {feb}, publisher = {Elsevier {BV}}, volume = {13}, number = {2}, pages = {150--158}, author = {St{'{e}}phane Haïk and Gabriella Marcon and Alain Mallet and Mauro Tettamanti and Arlette Welaratne and Giorgio Giaccone and Shohreh Azimi and Vladimiro Pietrini and Jean-Roch Fabreguettes and Daniele Imperiale and Pierre Cesaro and Carlo Buffa and Christophe Aucan and Ugo Lucca and Laur{`{e}}ne Peckeu and Silvia Suardi and Christine Tranchant and Inga Zerr and Caroline Houillier and Veronica Redaelli and Herv{'{e}} Vespignani and Angela Campanella and Fran{c{c}}ois Sellal and Anna Krasnianski and Danielle Seilhean and Uta Heinemann and Fr{'{e}}d{'{e}}ric Sedel and Mara Canovi and Marco Gobbi and Giuseppe Di Fede and Jean-Louis Laplanche and Maurizio Pocchiari and Mario Salmona and Gianluigi Forloni and Jean-Philippe Brandel and Fabrizio Tagliavini}, title = {Doxycycline in Creutzfeldt-Jakob disease: a phase 2, randomised, double-blind, placebo-controlled trial}, journal = {The Lancet Neurology} }


administration & dosage, adverse effects, aged, disease, double-blind method, doxycycline, drug therapy, early termination of clinical trials, female, genetics, humans, male, medical futility, middle aged, mortality, oral, pharmacology, treatment failure

Countries of Study

France, Italy

Types of Study

Randomised Controlled Trial

Type of Outcomes

Carer Burden (instruments measuring burden)

Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions