Glutamine Therapy for Hemolysis-Associated Pulmonary Hypertension

The primary hypothesis of this study is that glutamine supplementation will improve the erythrocyte glutamine/glutamate ratio, a biomarker of oxidative stress, hemolysis and pulmonary hypertension (PH) in sickle cell disease (SCD) and thalassemia (Thal) patients with PH. PH is defined as a tricuspid regurgitant jet velocity (TRV) on Doppler echocardiography > 2.5 m/s. We also predict that glutamine therapy will increase arginine bioavailability and subsequently alter sickle red cell endothelial interaction that can be identified using endo-PAT technology through nitric oxide (NO) generation, leading to changes in biological markers, and clinical outcome. Specifically our second hypothesis is that oral glutamine will decrease biomarkers of hemolysis and adhesion molecules, and improve the imbalanced arginine-to-ornithine ratio that occurs in hemolytic anemias, leading to improved arginine bioavailability and clinical endpoints of endothelial dysfunction and PH in patients with SCD and Thal.

The six-minute walk test (6MWT) measures the distance in meters an individual is able to walk over a total of six minutes on a hard, flat surface.

Inclusion Criteria: Established diagnosis of SCD (Hb SS, SC or SBeta- thalassemia) or Thal PH documented by echocardiography, defined as at TRV greater than 2.5 m/s Age greater than or equal to 4 years Exclusion Criteria: Inability to take or tolerate oral medication Acute crisis or hospitalization within 1 month of enrollment Hepatic dysfunction (SGPT greater than 3X normal) Renal dysfunction (Creatinine greater than 2X normal) Allergy to glutamine Pregnancy or breastfeeding Patients on sildenafil (Viagra), calcium channel blockers, or amino acid/protein supplements (other therapies acceptable if stable more than 3 months)