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abstracts & posters

A Phase 3 Study of L-Glutamine Therapy for Sickle Cell Anemia and Sickle ß0-Thalassemia

key information

source: Blood

year: 2014

authors: Yutaka Niihara, Han A. Koh, Lan Tran, Rafael Razon, Henry Macan, Charles Stark, Ted Wun, Patricia Adams-Graves


Background:There remains an unmet medical need for new treatments for patients with sickle cell disease (SCD). Increased oxidant stress plays a major part in the pathophysiology of sickle cell disease. It can lead to disturbance of cell membranes, exposure of adhesion molecules and damage to the contents of the sickle red blood cells (sRBC). Previous work from our laboratory has demonstrated enhancement of nicotinamide adenine dinucleotide (NAD) in sRBC by supplementation with a precursor of NAD, L-glutamine. A multi-center Phase 2 placebo-controlled trial in patients with SCD utilizing oral prescription grade L-glutamine resulted in a trend for a decrease in the incidence of painful crises at 24 weeks and a statistically significant decrease in hospitalization during the same time period in the L-glutamine group without increased adverse events. Based on these results, a large multicenter Phase 3 clinical trial was undertaken to evaluate the efficacy and safety of prescription grade L-glutamine therapy in patients with SCD.

Methods: A randomized (2:1), double-blind, placebo-controlled, parallel-group trial was conducted at 31 sites across the United States. Subjects were stratified by hydroxyurea usage. Eligibility criteria included patients >= 5 years of age with documented diagnoses of HbSS or HbS/β0-thalassemia with at least two documented episodes of sickle cell crises (SCC) diagnosed in a medical facility during the 12 months prior to screening. Pregnant women and patients with uncontrolled liver disease or renal insufficiency were excluded. Prescription grade L-glutamine at 0.6 g/kg/day (max 30 g), or placebo, was taken in two divided doses. Daily dose was rounded to the closest 10 g. The study drug was given for 48 weeks, then was tapered to zero over 3 weeks and a final evaluation visit was made 2 weeks after last dose. The primary endpoint was number of SCC; secondary endpoints include rates of hospitalization and adverse events; additional analyses include cumulative hospital days, incidence of acute chest syndrome (ACS) and time to first crises.

organization: Emmaus Medical, Inc, Torrance; Kaiser Permanente, Bellflower; University of California - Davis School of Medicine; University of Tennessee

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