OBJECTIVE: To determine whether oral quinacrine increases survival in sporadic Creutzfeldt-Jakob disease (sCJD). METHODS: This NIH/National Institute on Aging-funded, double-blinded, placebo-controlled, stratified randomization treatment trial was conducted at the University of California, San Francisco from February 2005 through May 2009 (ClinicalTrials.gov, NCT00183092). Subjects were randomized (50:50) to quinacrine (300 mg daily) or placebo with inpatient evaluations at baseline, and planned for months 2, 6, and 12. Subjects returning for their month-2 visit were offered open-label quinacrine. The primary outcome was survival from randomization to month 2. RESULTS: Of 425 patients referred, 69 subjects enrolled, 54 subjects were randomized to active drug or placebo, and 51 subjects with sCJD were included in survival analyses. Survival for the randomized portion of the trial (first 2 months) showed no significant difference between the 2 groups (log-rank statistic, p = 0.43; Cox proportional relative hazard = 1.43, quinacrine compared with placebo, 95% confidence interval = 0.58, 3.53). The quinacrine-treated group, however, declined less on 2 of 3 functional scales, the modified Rankin and Clinical Dementia Rating, than the placebo group during the first 2 months. CONCLUSION: This interventional study provides Class I evidence that oral quinacrine at 300 mg per day does not improve 2-month survival of patients with sCJD, compared with placebo. Importantly, this study shows that double-blinded, placebo-controlled, randomized treatment trials are possible in prion disease. Furthermore, the quantitative data collected on the course of sCJD will be useful for future trials. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that quinacrine does not improve survival for people with sCJD when given orally at a dose of 300 mg per day for 2 months.
RCT Entities:
OBJECTIVE: To determine whether oral quinacrine increases survival in sporadic Creutzfeldt-Jakob disease (sCJD). METHODS: This NIH/National Institute on Aging-funded, double-blinded, placebo-controlled, stratified randomization treatment trial was conducted at the University of California, San Francisco from February 2005 through May 2009 (ClinicalTrials.gov, NCT00183092). Subjects were randomized (50:50) to quinacrine (300 mg daily) or placebo with inpatient evaluations at baseline, and planned for months 2, 6, and 12. Subjects returning for their month-2 visit were offered open-label quinacrine. The primary outcome was survival from randomization to month 2. RESULTS: Of 425 patients referred, 69 subjects enrolled, 54 subjects were randomized to active drug or placebo, and 51 subjects with sCJD were included in survival analyses. Survival for the randomized portion of the trial (first 2 months) showed no significant difference between the 2 groups (log-rank statistic, p = 0.43; Cox proportional relative hazard = 1.43, quinacrine compared with placebo, 95% confidence interval = 0.58, 3.53). The quinacrine-treated group, however, declined less on 2 of 3 functional scales, the modified Rankin and Clinical Dementia Rating, than the placebo group during the first 2 months. CONCLUSION: This interventional study provides Class I evidence that oral quinacrine at 300 mg per day does not improve 2-month survival of patients with sCJD, compared with placebo. Importantly, this study shows that double-blinded, placebo-controlled, randomized treatment trials are possible in prion disease. Furthermore, the quantitative data collected on the course of sCJD will be useful for future trials. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that quinacrine does not improve survival for people with sCJD when given orally at a dose of 300 mg per day for 2 months.
Authors: D G Altman; K F Schulz; D Moher; M Egger; F Davidoff; D Elbourne; P C Gøtzsche; T Lang Journal: Ann Intern Med Date: 2001-04-17 Impact factor: 25.391
Authors: Sina Ghaemmaghami; Joel C Watts; Hoang-Oanh Nguyen; Shigenari Hayashi; Stephen J DeArmond; Stanley B Prusiner Journal: J Mol Biol Date: 2011-08-04 Impact factor: 5.469
Authors: Yong Huang; Hideaki Okochi; Barnaby C H May; Giuseppe Legname; Stanley B Prusiner; Leslie Z Benet; B Joseph Guglielmo; Emil T Lin Journal: Drug Metab Dispos Date: 2006-03-31 Impact factor: 3.922
Authors: Sina Ghaemmaghami; Misol Ahn; Pierre Lessard; Kurt Giles; Giuseppe Legname; Stephen J DeArmond; Stanley B Prusiner Journal: PLoS Pathog Date: 2009-11-26 Impact factor: 6.823
Authors: Sonia M Vallabh; Chloe K Nobuhara; Franc Llorens; Inga Zerr; Piero Parchi; Sabina Capellari; Eric Kuhn; Jacob Klickstein; Jiri G Safar; Flavia C Nery; Kathryn J Swoboda; Michael D Geschwind; Henrik Zetterberg; Steven E Arnold; Eric Vallabh Minikel; Stuart L Schreiber Journal: Proc Natl Acad Sci U S A Date: 2019-04-01 Impact factor: 11.205
Authors: Simon Mead; Matthew Burnell; Jessica Lowe; Andrew Thompson; Ana Lukic; Marie-Claire Porter; Christopher Carswell; Diego Kaski; Janna Kenny; Tze How Mok; Nina Bjurstrom; Edit Franko; Michele Gorham; Ronald Druyeh; Jonathan D F Wadsworth; Zane Jaunmuktane; Sebastian Brandner; Harpreet Hyare; Peter Rudge; A Sarah Walker; John Collinge Journal: JAMA Neurol Date: 2016-04 Impact factor: 18.302
Authors: Subhradip Mukhopadhyay; Toni M Antalis; Khanh P Nguyen; Mark H Hoofnagle; Rajabrata Sarkar Journal: Blood Date: 2017-03-20 Impact factor: 22.113