Trial of celecoxib in amyotrophic lateral sclerosis

被引:227
作者
Cudkowicz, Merit E.
Shefner, Jeremy M.
Schoenfeld, David A.
Zhang, Hui
Andreasson, Katrin I.
Rothstein, Jeffrey D.
Drachman, Daniel B.
机构
[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Trials Unit, Charlestown, MA 02172 USA
[2] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02172 USA
[3] Upstate Med Univ, Syracuse, NY USA
[4] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Biostat Ctr,Dept Med, Boston, MA USA
[5] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA
关键词
D O I
10.1002/ana.20903
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: To determine whether chronic treatment with celecoxib, a cyclooxygenase-2 inhibitor that has been shown to be beneficial in preclinical testing, is safe and effective in amyotrophic lateral sclerosis (ALS). Methods: A double-blind, placebo-controlled, clinical trial was conducted. Three hundred research subjects with ALS were randomized (2:1) to receive celecoxib (800mg/day) or placebo for 12 months. The primary outcome measure was the rate of change in upper extremity motor function measured by the maximum voluntary isometric contraction strength. Secondary end points included safety, survival, change in cerebrospinal fluid prostaglandin E, levels, and changes in the rate of decline of leg and grip strength, vital capacity, ALS Functional Rating Scale-Revised, and motor unit number estimates. Results: Celecoxib did not slow the decline in muscle strength, vital capacity, motor unit number estimates, ALS Functional Rating Scale-Revised, or affect survival. Celecoxib was well tolerated and was not associated with an increased frequency of adverse events. Prostaglandin E, levels in cerebrospinal fluid were not elevated at baseline and did not decline with treatment. Interpretation: At the dosage studied, celecoxib did not have a beneficial effect on research subjects with ALS, and it was safe. A biological effect of celecoxib was not demonstrated in the cerebrospinal fluid. Further studies of celecoxib at a dosage of 800mg/day in ALS are not warranted.
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页码:22 / 31
页数:10
相关论文
共 37 条
[1]   Increased levels of the pro-inflammatory prostaglandin PGE2 in CSF from ALS patients [J].
Almer, G ;
Teismann, P ;
Stevic, Z ;
Halaschek-Wiener, J ;
Deecke, L ;
Kostic, V ;
Przedborski, S .
NEUROLOGY, 2002, 58 (08) :1277-1279
[2]  
Almer G, 2001, ANN NEUROL, V49, P176, DOI 10.1002/1531-8249(20010201)49:2<176::AID-ANA37>3.3.CO
[3]  
2-O
[4]   QUANTITATIVE ASSESSMENT OF NEUROMUSCULAR DEFICIT IN ALS [J].
ANDRES, PL ;
THIBODEAU, LM ;
FINISON, LJ ;
MUNSAT, TL .
NEUROLOGIC CLINICS, 1987, 5 (01) :125-141
[5]  
[Anonymous], CLIN RES REGUL AFF
[6]   Effects of intraperitoneal injection of Rofecoxib in a mouse model of ALS [J].
Azari, MF ;
Profyris, C ;
Le Grande, MR ;
Lopes, EC ;
Hirst, J ;
Petratos, S ;
Cheema, SS .
EUROPEAN JOURNAL OF NEUROLOGY, 2005, 12 (05) :357-364
[7]   Prostaglandins stimulate calcium-dependent glutamate release in astrocytes [J].
Bezzi, P ;
Carmignoto, G ;
Pasti, L ;
Vesce, S ;
Rossi, D ;
Rizzini, BL ;
Pozzan, T ;
Volterra, A .
NATURE, 1998, 391 (6664) :281-285
[8]   PGE2 receptors rescue motor neurons in a model of amyotrophic lateral sclerosis [J].
Bilak, M ;
Wu, LJ ;
Wang, Q ;
Haughey, N ;
Conant, K ;
Hillaire, CS ;
Andreasson, K .
ANNALS OF NEUROLOGY, 2004, 56 (02) :240-248
[9]   Increased oxidative damage to DNA in ALS patients [J].
Bogdanov, M ;
Brown, RH ;
Matson, W ;
Smart, R ;
Hayden, D ;
O'Donnell, H ;
Beal, MF ;
Cudkowicz, M .
FREE RADICAL BIOLOGY AND MEDICINE, 2000, 29 (07) :652-658
[10]   Sources of reactive oxygen species production in excitotoxin-stimulated cerebellar granule cells [J].
Boldyrev, AA ;
Carpenter, DO ;
Huentelman, MJ ;
Peters, CM ;
Johnson, P .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 256 (02) :320-324