Oral L-glutamine therapy significantly reduces pain crises associated with sickle cell disease compared with placebo regardless of patient hydroxyurea use, according to a study published in the New England Journal of Medicine.
A multicenter, randomized, placebo-regulated, double-blind, parallel phase 3 trial was conducted to determine if L-glutamine administration could reduce pain crises better than placebo in patients with sickle cell anemia or sickle β0-thalassemia. The researchers were also interested in assessing outcomes with L-glutamine vs placebo in the presence and absence of hydroxyurea among individuals with sickle cell disease.
The main outcome studied was reported pain crises among participants until week 48. Sickle cell-related events included acute chest syndrome, priapism, and splenic sequestration.
Secondary outcomes included number of hospitalizations and number of emergency department visits for pain related to sick cell disease, as well as fluctuations in hematologic levels from baseline.
Patients were arbitrarily sorted to receive either L-glutamine (0.3 g per kg of body weight per dose) or placebo (100% maltodextrin) administered orally twice a day for 48 days. Patients who received stable hydroxyurea doses for at least 3 months prior to analysis continued to receive treatment for the duration of the 48-week study.
Of the original 230 participants chosen (aged 5 to 58 years; 53.9% women), 156 completed the study: 97 of 152 participants in the L-glutamine cohort (63.8%) completed the study, as did 59 of 78 participants in the placebo cohort (75.6%). Concomitant hydroxyurea was administered to approximately 66% of patients in both groups.
Results suggested that patients in the L-glutamine group had significantly less reported pain crises than patients in the control group, with medians of 3.0 and 4.0 in the case and control groups, respectively. In addition, fewer hospitalizations were reported in the L-glutamine group (2.0) compared with the placebo group (3.0); however, reports of nausea, noncardiac chest pain, fatigue, and musculoskeletal pain were more frequent in the L-glutamine group than the placebo group.
“On the basis of the results of this phase 3 trial, the [US Food and Drug Administration] granted approval of pharmaceutical grade L-glutamine (Endari, Emmaus Medical) as a prescription drug to reduce the rate of acute complications of sickle cell disease among adults and children 5 years of age and older,” the authors concluded.
Disclosure: This study was supported by Emmaus Medical. Please refer to the full text for a listing of author disclosures.
Niihara Y, Miller ST, Kanter J, et al; for the Investigators of the Phase 3 Trial of L-Glutamine in Sickle Cell Disease. A phase 3 trial of L-glutamine in sickle cell disease [published online July 19, 2018]. N Eng J Med. doi: 10.1056/NEJMoad1715971