A Phase 3 Trial of l-Glutamine in Sickle Cell Disease.
Publication/Presentation Date
7-19-2018
Abstract
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 β
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. (Funded by Emmaus Medical; ClinicalTrials.gov number, NCT01179217 .).
Volume
379
Issue
3
First Page
226
Last Page
235
ISSN
1533-4406
Published In/Presented At
Niihara, Y., Miller, S. T., Kanter, J., Lanzkron, S., Smith, W. R., Hsu, L. L., Gordeuk, V. R., Viswanathan, K., Sarnaik, S., Osunkwo, I., Guillaume, E., Sadanandan, S., Sieger, L., Lasky, J. L., Panosyan, E. H., Blake, O. A., New, T. N., Bellevue, R., Tran, L. T., Razon, R. L., … Investigators of the Phase 3 Trial of l-Glutamine in Sickle Cell Disease (2018). A Phase 3 Trial of l-Glutamine in Sickle Cell Disease. The New England journal of medicine, 379(3), 226–235. https://doi.org/10.1056/NEJMoa1715971
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
30021096
Department(s)
Administration and Leadership
Document Type
Article