Arginine Therapy (STArT) Trial

Vaso-occlusive painful episodes (VOE) in sickle cell disease (SCD) are the leading cause of hospitalizations, emergency room (ED) visits, and missed school, and are associated with an increased mortality rate. There are no current therapies to relieve vaso-occlusion, with interventions limited to hydration and analgesia. Nitric oxide (NO), produced by the 5-electron oxidation of L-arginine, is a potent vasodilator and exerts pleiotropic effects on vascular and circulating blood cells, including the inhibition of platelet aggregation, down-regulation of adhesion molecules, and modulation of ischemia-reperfusion injury, all pathways adversely affected during VOE. In previous trials it has been found that pediatric SCD patients admitted with VOE have depleted plasma L-arginine levels. Additionally, a single-center randomized, double-blinded, placebo-controlled trial of arginine therapy in 54 children with VOE requiring hospitalization was completed. A reduction in total opioid use (mg/kg) by 54% and significantly lower pain scores at discharge in children who received 5 days IV L-arginine therapy every 8 hours compared to placebo, as well as a clinically relevant trend in reduced length of hospital stay of approximately 17 hours was observed. In pharmacokinetic studies, it was found that IV arginine induced a dose-dependent improvement in mitochondrial function in children with SCD hospitalized for pain. The purpose of this study is to determine whether IV arginine will help shorten how long pain lasts for people having a sickle cell related pain episode.