Safety and Efficacy of L-Glutamine in Reducing the Frequency of Acute Complications Among Patients with Sickle Cell Disease: A Randomized Controlled Study

Abstract Introduction Patients with sickle cell disease (SCD) suffer from recurrent and unpredictable episodes of acute pain due to vaso-occlusive crisis (VOC) which may require hospitalization and they also develop chronic persistent pain. Since pain usually begins in infancy and continues throughout life, preventing the genesis of pain is comparatively higher than treating the pain once it has been evoked VOC represents the cause of almost 95% of hospitalizations for patients with SCD. L-glutamine is an amino acid needed for the synthesis of the pyridines for nucleotides, including nicotinamide adenine dinucleotide (NAD) and glutathione, in addition to glutamate, and becomes essential during oxidative stress exposure. The NADH: [NAD+ + NADH] (redox) ratio in sickle red blood cells (RBCs) is lower than in normal RBCs which is related to oxidative stress, so L-glutamine availability is important in SCD. Although the FDA-approved it for preventing acute complications in SCD, still has many gaps in our understanding of its therapeutic implications. Aim To evaluate the safety and efficacy of L-glutamine in reducing the number of VOCs in patients with SCD. Methods This is an investigator-initiated single-center phase 4 interventional randomized controlled trial at Ain Shams Pediatric Hematology Unit. Sixty SCD participants, their mean age was 9.2 ± 3.7 years, they were 35 males and 25 females, were randomly assigned in a 1:1 ratio to receive glutamine at a dose of 0.3 gm/kg/dose twice daily orally (up to a maximum of 15 g/dose) for 24 weeks or the standard of care (SOC) without glutamine intake. Results Thirty-seven (62%) had HbSS with 38% had other sickle cell variants. All participants were receiving HU therapy and were on stable dose during the last three months prior to enrollment. Almost half of the patients (48%) were on chelation therapy with deferasirox. Thirty SCD patients were recruited in each group either received glutamine or SOC, both groups were comparable as regards demographic data. All patients in both arms had VOCs in the last year more than two. For the primary endpoint, there was a decreasing trend in the number, severity, and hospitalization of VOC in the glutamine arm and there was a significantly lower cumulative number of VOCs in the glutamine group (38.9%) than SOC (52.8%) (p = 0.008) and lower cumulative number of hospitalizations (p < 0.001). Conclusion Glutamine reduced the number of VOCs and hospitalizations for VOC in our cohort with SCD.