A Phase 3 Trial of L-Glutamine in Sickle Cell Disease

作者：Niihara, Yutaka; Miller, Scott T.; Kanter, Julie; Lanzkron, Sophie; Smith, Wally R.; Hsu, Lewis L.; Gordeuk, Victor R.; Viswanathan, Kusum; Sarnaik, Sharada; Osunkwo, Ifeyinwa; Guillaume, Edouard; Sadanandan, Swayam; Sieger, Lance; Lasky, Joseph L.; Panosyan, Eduard H.; Blake, O**ourne A.; New, Tamara N.; Bellevue, Rita; Tran, Lan T.; Razon, Rafael L.; Stark, Charles W.^*; Neumayr, Lynne D.; Vichinsky, Elliott P.

来源：New England Journal of Medicine, 2018, 379(3): 226-235.

DOI：10.1056/NEJMoa1715971

• ACUTE CHEST SYNDROME
• PULMONARY-HYPERTENSION
• ANEMIA
• HYDROXYUREA
• REGRESSION
• CRISES

BACKGROUND @@@ Oxidative stress contributes to the complex pathophysiology of sickle cell disease. Oral therapy with pharmaceutical-grade L-glutamine (USAN, glutamine) has been shown to increase the proportion of the reduced form of nicotinamide adenine dinucleotides in sickle cell erythrocytes, which probably reduces oxidative stress and could result in fewer episodes of sickle cell-related pain. @@@ METHODS @@@ In a multicenter, randomized, placebo-controlled, double-blind, phase 3 trial, we tested the efficacy of pharmaceutical-grade L-glutamine (0.3 g per kilogram of body weight per dose) administered twice daily by mouth, as compared with placebo, in reducing the incidence of pain crises among patients with sickle cell anemia or sickle jr-thalassemia and a history of two or more pain crises during the previous year. Patients who were receiving hydroxyurea at a dose that had been stable for at least 3 months before screening continued that therapy through the 48-week treatment period. @@@ RESULTS @@@ A total of 230 patients (age range, 5 to 58 years; 53.9% female) were randomly assigned, in a 2:1 ratio, to receive L-glutamine (152 patients) or placebo (78 patients). The patients in the L-glutamine group had significantly fewer pain crises than those in the placebo group (P=0.005), with a median of 3.0 in the L-glutamine group and 4.0 in the placebo group. Fewer hospitalizations occurred in the L-glutamine group than in the placebo group (P=0.005), with a median of 2.0 in the L-glutamine group and 3.0 in the placebo group. Two thirds of the patients in both trial groups received concomitant hydroxyurea. Low-grade nausea, noncardiac chest pain, fatigue, and musculoskeletal pain occurred more frequently in the L-glutamine group than in the placebo group. @@@ CONCLUSIONS @@@ Among children and adults with sickle cell anemia, the median number of pain crises over 48 weeks was lower among those who received oral therapy with L-glutamine, administered alone or with hydroxyurea, than among those who received placebo, with or without hydroxyurea.

• 出版日期2018-7-19